Presented by Risa Mann, M.D. and prepared by Angelique W. Levi, M.D.
Case 1: 40-year-old woman with lymph node enlargement
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Week 11: Case 1
40-year-old woman with lymph node enlargement
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Correct
Answer: Ki-1 positive large cell lymphoma
Histology: The specimen is a lymph node that shows reactive hyperplasia. However, within the sinuses there is a proliferation of large atypical cells. The cells have abundant cytoplasm and large nuclei often with prominent nucleoli. Some of the cells have multiple nuclei and others show a horseshoe ring-like appearance. There does not appear to be a proliferation of other inflammatory cells such as eosinophils or plasma cells associated with the proliferation. Also, there is no pigment present within the cells. Scattered mitotic figures are observed. The tumor cells appear to primarily involve the sinuses.
Discussion: In metastatic carcinoma to lymph nodes, the tumor would involve and fill the sinuses, as in this case. However, in metastatic carcinoma, the cells are more cohesive and often show evidence of epithelial differentiation such as gland formation or squamous differentiation. In this tumor, the cells are non-cohesive. This tumor can be easily confused with metastatic malignant melanoma because the cells are large and often have a prominent nuclei and maybe binucleated. However, the tumor cells in ki-1 lymphoma lack pigment on H&E stain and do not show evidence of melanin production using special staining techniques. Hodgkin’s Disease can involve the sinuses, but is not usually primarily localized to the sinuses. In addition, Hodgkin’s Disease usually has other inflammatory cells associated with it, such as plasma cells and eosinophils. Immunohistochemical staining can be particularly helpful in establishing the diagnosis of ki-1 lymphoma. The neoplastic cells stain with CD30 (ki-1). They are +/- with epithelial membrane antigen. This fact is important since the differential diagnosis does include metastatic carcinomas which can be positive for EMA, but in general, most epithelial tumors are ki-1 negative. The tumor cells in a ki-1 positive lymphoma also show evidence of T-cell differentiation and are CD3 positive, and lack keratin expression. Additionally, the cells in some cases of ki-1 lymphoma stain for alk protein, the product of the t(2:5) translocation that has been associated with ki-1+ large cell lymphoma. The tumor can be distinguished from Hodgkin’s Disease because classic Reed-Sternberg cells are not usually very prominent. In addition, the cells of Hodgkin’s Disease are usually negative for CLA and stain positively for CD15 as well as CD30. Reed-Sternberg cells may on occasion be positive for CD20. Of course the cells in carcinoma would stain for various keratins and the cells of malignant melanoma would stain positive for S100, melan A and HMB45.
Incorrect
Answer: Ki-1 positive large cell lymphoma
Histology: The specimen is a lymph node that shows reactive hyperplasia. However, within the sinuses there is a proliferation of large atypical cells. The cells have abundant cytoplasm and large nuclei often with prominent nucleoli. Some of the cells have multiple nuclei and others show a horseshoe ring-like appearance. There does not appear to be a proliferation of other inflammatory cells such as eosinophils or plasma cells associated with the proliferation. Also, there is no pigment present within the cells. Scattered mitotic figures are observed. The tumor cells appear to primarily involve the sinuses.
Discussion: In metastatic carcinoma to lymph nodes, the tumor would involve and fill the sinuses, as in this case. However, in metastatic carcinoma, the cells are more cohesive and often show evidence of epithelial differentiation such as gland formation or squamous differentiation. In this tumor, the cells are non-cohesive. This tumor can be easily confused with metastatic malignant melanoma because the cells are large and often have a prominent nuclei and maybe binucleated. However, the tumor cells in ki-1 lymphoma lack pigment on H&E stain and do not show evidence of melanin production using special staining techniques. Hodgkin’s Disease can involve the sinuses, but is not usually primarily localized to the sinuses. In addition, Hodgkin’s Disease usually has other inflammatory cells associated with it, such as plasma cells and eosinophils. Immunohistochemical staining can be particularly helpful in establishing the diagnosis of ki-1 lymphoma. The neoplastic cells stain with CD30 (ki-1). They are +/- with epithelial membrane antigen. This fact is important since the differential diagnosis does include metastatic carcinomas which can be positive for EMA, but in general, most epithelial tumors are ki-1 negative. The tumor cells in a ki-1 positive lymphoma also show evidence of T-cell differentiation and are CD3 positive, and lack keratin expression. Additionally, the cells in some cases of ki-1 lymphoma stain for alk protein, the product of the t(2:5) translocation that has been associated with ki-1+ large cell lymphoma. The tumor can be distinguished from Hodgkin’s Disease because classic Reed-Sternberg cells are not usually very prominent. In addition, the cells of Hodgkin’s Disease are usually negative for CLA and stain positively for CD15 as well as CD30. Reed-Sternberg cells may on occasion be positive for CD20. Of course the cells in carcinoma would stain for various keratins and the cells of malignant melanoma would stain positive for S100, melan A and HMB45.
Presented by Risa Mann, M.D. and prepared by Angelique W. Levi, M.D.
Case 2: 18-year-old male with a mediastinal mass
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Week 11: Case 2
18-year-old male with a mediastinal mass
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Answer: Lymphoblastic lymphoma
Histology: The mass is composed of a relatively diffuse proliferation of small lymphoid cells. The nuclei have a rather blastic appearance and brisk mitotic rate. There are occasional histiocytes mixed within the tumor. There are no large or bizarre atypical cells with prominent nucleoli, nor does there appear to be any evidence of epithelial differentiation within the tumor.
Discussion: Based on the relatively small size of the cells, the tumor appears to be a lymphoid proliferation. The brisk mitotic rate is typical of an aggressive tumor. In general, the diffuse aggressive tumors which occur in the mediastinum would include a lymphoblastic lymphoma or a large cell lymphoma. The small size of the cells as well the lack of prominent nucleoli would rule out the possibility of a mediastinal large B-cell lymphoma. In addition, immunophenotyping would be helpful in distinguishing this tumor from other lymphomas. This tumor is a T-cell tumor that reacts with CD3 and other pan T-cell markers. In addition, it is also a TDT positive. The mediastinal large cell lymphoma usually demonstrates a B-phenotype which would be unusual for lymphoblastic lymphomas although there are some cases of pre B-cell lymphoblastic lymphomas. This tumor is easily distinguished from Hodgkin’s Disease in that it is composed of immature cells whereas the background cells in Hodgkin’s are mature T-cells and do not demonstrate the brick mitotic rate seen in this tumor. Lastly, this lesion needs to be distinguished from mediastinal thymomas. Although the background cells in thymomas are predominantly T-lymphocytes, they are usually more mature in appearance and do not demonstrate as brisk a mitotic rate as seen in lymphoblastic lymphoma. In addition, the hallmark of a thymoma is the presence of the epithelial cells which are the neoplastic component of a thymoma. If these are not readily appreciated on H&E, they can usually be appreciated using cytokeratin stains.
Incorrect
Answer: Lymphoblastic lymphoma
Histology: The mass is composed of a relatively diffuse proliferation of small lymphoid cells. The nuclei have a rather blastic appearance and brisk mitotic rate. There are occasional histiocytes mixed within the tumor. There are no large or bizarre atypical cells with prominent nucleoli, nor does there appear to be any evidence of epithelial differentiation within the tumor.
Discussion: Based on the relatively small size of the cells, the tumor appears to be a lymphoid proliferation. The brisk mitotic rate is typical of an aggressive tumor. In general, the diffuse aggressive tumors which occur in the mediastinum would include a lymphoblastic lymphoma or a large cell lymphoma. The small size of the cells as well the lack of prominent nucleoli would rule out the possibility of a mediastinal large B-cell lymphoma. In addition, immunophenotyping would be helpful in distinguishing this tumor from other lymphomas. This tumor is a T-cell tumor that reacts with CD3 and other pan T-cell markers. In addition, it is also a TDT positive. The mediastinal large cell lymphoma usually demonstrates a B-phenotype which would be unusual for lymphoblastic lymphomas although there are some cases of pre B-cell lymphoblastic lymphomas. This tumor is easily distinguished from Hodgkin’s Disease in that it is composed of immature cells whereas the background cells in Hodgkin’s are mature T-cells and do not demonstrate the brick mitotic rate seen in this tumor. Lastly, this lesion needs to be distinguished from mediastinal thymomas. Although the background cells in thymomas are predominantly T-lymphocytes, they are usually more mature in appearance and do not demonstrate as brisk a mitotic rate as seen in lymphoblastic lymphoma. In addition, the hallmark of a thymoma is the presence of the epithelial cells which are the neoplastic component of a thymoma. If these are not readily appreciated on H&E, they can usually be appreciated using cytokeratin stains.
Presented by Risa Mann, M.D. and prepared by Angelique W. Levi, M.D.
Case 3: 45 year-old with parotid mass
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Week 11: Case 3
45 year-old with parotid mass
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Answer: Monomorphic adenoma
Histology: The tumor is a well-circumscribed mass occurring in the parotid gland. The tumor appears to be encapsulated. It is composed of nests of epithelial cells which grow in chords and sheets. Some of the areas that demonstrate palisading of the cells at the periphery give rise to a somewhat “basaloid” appearance. The tumor lacks evidence of myxoid proliferation. These cells are rather bland in appearance and lack mitotic activity or cytologic atypia.
Discussion: This tumor can easily be distinguished from the more common pleomorphic adenoma (mixed tumor) which has an extremely variable histology with numerous patterns of proliferation including epithelial and mesenchymal components. This tumor is predominately epithelial in appearance and as the name implies is also monomorphic in appearance. The circumscription allows one to distinguish it from a higher-grade tumor, such as a metastatic adenocarcinoma or adenoid cystic carcinoma, which usually have a classic cribriform appearance with prominent invasion of nerves. Metastatic carcinoma might show evidence of vascular invasion within the parotid gland and would usually demonstrate a more aggressive growth pattern, as well as more cytologic atypia.
Incorrect
Answer: Monomorphic adenoma
Histology: The tumor is a well-circumscribed mass occurring in the parotid gland. The tumor appears to be encapsulated. It is composed of nests of epithelial cells which grow in chords and sheets. Some of the areas that demonstrate palisading of the cells at the periphery give rise to a somewhat “basaloid” appearance. The tumor lacks evidence of myxoid proliferation. These cells are rather bland in appearance and lack mitotic activity or cytologic atypia.
Discussion: This tumor can easily be distinguished from the more common pleomorphic adenoma (mixed tumor) which has an extremely variable histology with numerous patterns of proliferation including epithelial and mesenchymal components. This tumor is predominately epithelial in appearance and as the name implies is also monomorphic in appearance. The circumscription allows one to distinguish it from a higher-grade tumor, such as a metastatic adenocarcinoma or adenoid cystic carcinoma, which usually have a classic cribriform appearance with prominent invasion of nerves. Metastatic carcinoma might show evidence of vascular invasion within the parotid gland and would usually demonstrate a more aggressive growth pattern, as well as more cytologic atypia.
Presented by Risa Mann, M.D. and prepared by Angelique W. Levi, M.D.
Case 4: 43 year-old male with shoulder mass
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Week 11: Case 4
43 year-old male with shoulder mass
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Answer: Schwannoma
Histology: The mass is a well-circumscribed tumor composed of spindle cells, which in some areas are densely cellular and in other areas the proliferation is rather loose and acellular. In some areas, the cells appear to line up and palisade giving rise to Verocay bodies. The tumor cells are relatively bland in appearance. Mitoses are not prominent. There are scattered thick walled vessels present. The densely cellular and less cellular areas are referred to as Antoni A and Antoni B type tissue, respectively.
Discussion: The well defined nature of this tumor as well as the Antoni A and Antoni B areas of proliferation are characteristic of schwannoma. A neurofibroma would usually be less well circumscribed and lack the loose and more dense areas as seen in Schwannoma. In addition, Verocay bodies and palisading of nuclei as well as thickening of vessels are not usually present in neurofibromas. Traumatic neuromas are usually associated with fibrosis and disorganized proliferation of small nerves with visible myelin sheaths. Fibrous histiocytoma is composed of a mixture of fibrous and histiocytic cells, also lacking Verocay bodies and thick walled blood vessels. Nuclei are not as elongated in fibrous histiocytoma as in neural tumors. Immunohistochemically, the schwannoma would stain for S100. These tumors may become cellular, but malignant transformation is rare.
Incorrect
Answer: Schwannoma
Histology: The mass is a well-circumscribed tumor composed of spindle cells, which in some areas are densely cellular and in other areas the proliferation is rather loose and acellular. In some areas, the cells appear to line up and palisade giving rise to Verocay bodies. The tumor cells are relatively bland in appearance. Mitoses are not prominent. There are scattered thick walled vessels present. The densely cellular and less cellular areas are referred to as Antoni A and Antoni B type tissue, respectively.
Discussion: The well defined nature of this tumor as well as the Antoni A and Antoni B areas of proliferation are characteristic of schwannoma. A neurofibroma would usually be less well circumscribed and lack the loose and more dense areas as seen in Schwannoma. In addition, Verocay bodies and palisading of nuclei as well as thickening of vessels are not usually present in neurofibromas. Traumatic neuromas are usually associated with fibrosis and disorganized proliferation of small nerves with visible myelin sheaths. Fibrous histiocytoma is composed of a mixture of fibrous and histiocytic cells, also lacking Verocay bodies and thick walled blood vessels. Nuclei are not as elongated in fibrous histiocytoma as in neural tumors. Immunohistochemically, the schwannoma would stain for S100. These tumors may become cellular, but malignant transformation is rare.
Presented by Risa Mann, M.D. and prepared by Angelique W. Levi, M.D.
Case 5: 54 year-old man with syncope
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Week 11: Case 5
54 year-old man with syncope
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Answer: Subependymoma
Histology: The tumor is a glial proliferation composed of round to oval cells in a pale glial mesh background. Occasional cysts are seen throughout the tumor. The tumor cells have a distinctive pattern with the cells proliferating in small groups or nests. Rosettes, atypia and mitoses are not seen.
Discussion: This tumor is composed of an ill-defined glial proliferation. The striking feature of this lesion is the pattern of proliferation of the cells within the glial background matrix. The tumor cells are round to oval and are cytologically bland. The cells characteristically nest or cluster in small groups. This patterning of the cells is very distinctive for subependymomas and is not seen in astrocytomas. The pattern of clustering of neoplastic cells allows one to distinguish this tumor from an oligodendroglioma or an astrocytoma. The lack of perinuclear halos or small vessel proliferation allows for distinction from an oligodendroglioma. This lesion can be distinguished from an ependymoma in that it lacks the typical perivascular rosette pattern seen in ependymomas. The majority of these tumors are located in the fourth ventricle usually arising from its floor. They are often incidentally discovered at autopsy, but occasionally these tumors may reach sufficient size to be associated with obstructive phenomena and symptomatology. They also may occur in other locations including the lateral ventricles. They only rarely involve the third ventricle or cerebral aqueduct. The tumor is usually non-invasive and is relatively well defined. Occasionally, these tumors may demonstrate extensive calcification.
Incorrect
Answer: Subependymoma
Histology: The tumor is a glial proliferation composed of round to oval cells in a pale glial mesh background. Occasional cysts are seen throughout the tumor. The tumor cells have a distinctive pattern with the cells proliferating in small groups or nests. Rosettes, atypia and mitoses are not seen.
Discussion: This tumor is composed of an ill-defined glial proliferation. The striking feature of this lesion is the pattern of proliferation of the cells within the glial background matrix. The tumor cells are round to oval and are cytologically bland. The cells characteristically nest or cluster in small groups. This patterning of the cells is very distinctive for subependymomas and is not seen in astrocytomas. The pattern of clustering of neoplastic cells allows one to distinguish this tumor from an oligodendroglioma or an astrocytoma. The lack of perinuclear halos or small vessel proliferation allows for distinction from an oligodendroglioma. This lesion can be distinguished from an ependymoma in that it lacks the typical perivascular rosette pattern seen in ependymomas. The majority of these tumors are located in the fourth ventricle usually arising from its floor. They are often incidentally discovered at autopsy, but occasionally these tumors may reach sufficient size to be associated with obstructive phenomena and symptomatology. They also may occur in other locations including the lateral ventricles. They only rarely involve the third ventricle or cerebral aqueduct. The tumor is usually non-invasive and is relatively well defined. Occasionally, these tumors may demonstrate extensive calcification.
Histology: The mass at low power appears to be lymphoid in nature. It has a vaguely nodular pattern of growth. The nodules have within the center of them a small germinal center-like structure. The germinal centers are often surrounded by small lymphocytes that palisade around the germinal center in an Indian file pattern. Many of the small germinal center-like structures have small vessels within them, some of which appear sclerotic. The germinal centers lack tingible body macrophages. The interfollicular area has a proliferation of small vessels and the lymphocytes surrounding the germinal centers appear to have a somewhat extended mantel zone.
Discussion: This is a classic example of the hyaline vascular type of Castleman’s Disease. The distinguishing feature is the presence of numerous small nodules which are composed of a hyalinized and vascularized germinal centers surrounded by small lymphocytes proliferating an Indian filing pattern. There is striking hyalinization and vascularization of the germinal centers as well as vascular proliferation in the interfollicular area. The lesion can be distinguished from follicular lymphoma because in follicular lymphoma the nodules are more proliferative and are composed of usually monotonous proliferation of small cleaved cells sometimes admixed with larger transformed lymphocytes. In addition, in follicular lymphoma, the neoplastic nodules are closer together in a back-to-back pattern and immunophenotypic studies would demonstrate a clonal proliferation of B-cells. The lesion can be distinguished from a non-specific reactive hyperplasia because in a non-specific follicular hyperplasia, one would expect to see larger germinal centers which would have more proliferative activity associated with tangible body macrophages. Reactive germinal centers often demonstrate polarization which is absent in the small germinal centers of Castleman’s Disease. The lesion can be also distinguished from a thymoma in that a thymoma would contain spindle cells or an epithelial proliferation which would also stain positive with keratin. The hyaline vascular type of Castleman’s Disease is the most common type of Castleman’s Disease and often presents in the mediastinum. These masses are often identified on routine chest x-ray in an otherwise asymptomatic patient. In addition to the localized Castleman’s disease, there are also cases of more generalized disease. Some of the patients with more generalized disease have a different histologic variety of Castleman’s Disease which is called plasma cell type of Castleman’s disease. In contrast to hyaline vascular Castleman’s disease, the plasma cell variant has rather large proliferative appearing germinal centers and the interfollicular area contains a sheet-like dense proliferation of plasma cells often associated with a vascular proliferation.
Histology: The mass at low power appears to be lymphoid in nature. It has a vaguely nodular pattern of growth. The nodules have within the center of them a small germinal center-like structure. The germinal centers are often surrounded by small lymphocytes that palisade around the germinal center in an Indian file pattern. Many of the small germinal center-like structures have small vessels within them, some of which appear sclerotic. The germinal centers lack tingible body macrophages. The interfollicular area has a proliferation of small vessels and the lymphocytes surrounding the germinal centers appear to have a somewhat extended mantel zone.
Discussion: This is a classic example of the hyaline vascular type of Castleman’s Disease. The distinguishing feature is the presence of numerous small nodules which are composed of a hyalinized and vascularized germinal centers surrounded by small lymphocytes proliferating an Indian filing pattern. There is striking hyalinization and vascularization of the germinal centers as well as vascular proliferation in the interfollicular area. The lesion can be distinguished from follicular lymphoma because in follicular lymphoma the nodules are more proliferative and are composed of usually monotonous proliferation of small cleaved cells sometimes admixed with larger transformed lymphocytes. In addition, in follicular lymphoma, the neoplastic nodules are closer together in a back-to-back pattern and immunophenotypic studies would demonstrate a clonal proliferation of B-cells. The lesion can be distinguished from a non-specific reactive hyperplasia because in a non-specific follicular hyperplasia, one would expect to see larger germinal centers which would have more proliferative activity associated with tangible body macrophages. Reactive germinal centers often demonstrate polarization which is absent in the small germinal centers of Castleman’s Disease. The lesion can be also distinguished from a thymoma in that a thymoma would contain spindle cells or an epithelial proliferation which would also stain positive with keratin. The hyaline vascular type of Castleman’s Disease is the most common type of Castleman’s Disease and often presents in the mediastinum. These masses are often identified on routine chest x-ray in an otherwise asymptomatic patient. In addition to the localized Castleman’s disease, there are also cases of more generalized disease. Some of the patients with more generalized disease have a different histologic variety of Castleman’s Disease which is called plasma cell type of Castleman’s disease. In contrast to hyaline vascular Castleman’s disease, the plasma cell variant has rather large proliferative appearing germinal centers and the interfollicular area contains a sheet-like dense proliferation of plasma cells often associated with a vascular proliferation.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 6: 55-year-old male with pleural effusions
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Week 3: Case 6
55-year-old male with pleural effusions
Correct
Answer: Malignant mesothelioma
Histology: Most of the lesion consists of a cellular spindle cell lesion with a collagenous appearance. The nuclei are fairly uniform and ovoid with visible nucleoli. Mitotic figures are present yet not frequent. In areas, the lesion dissects through the fat leaving entrapped adipocytes. Within the fat, focal glandular structures were identified. The biphasic nature of this lesion composed of epithelial and spindle cell components is diagnostic of a biphasic malignant mesothelioma. Stains for cytokeratin and calretinin were strongly positive both within the spindle cell component as well as within the tubular structures.
Discussion: In contrast to reactive pleural fibrosis, this lesion lacks a significant inflammatory component. Reactive pleural fibrosis may demonstrate mesothelial hyperplasia consisting of tubules. However, these tubules are seen closer to the pleural surface and associated with inflammation. The histology of cellular fibrous tissue dissecting the adipose tissue would also not be expected in a reactive process. The presence of keratin within the spindle cell component does not distinguish reactive pleural fibrosis from malignant mesothelioma as reactive pleural “fibrosis” results from a proliferation of submesothelial cells that also express keratin. A fibromatosis would have a much more uniform growth appearance consisting of long sweeping fascicles of fibrous tissue. The presence of a glandular component rules out fibromatosis. Epithelioid hemangioendothelioma is a low-grade vascular malignancy that lacks a prominent cellular spindled cell component. Rather, it typically consists of epithelioid appearing cells often with a single cytoplasmic vacuole set in a dense hyalinized fibrotic background. Gland formation is not identified. Epithelioid hemangioendotheliomas can express keratin in addition to vascular markers.
Incorrect
Answer: Malignant mesothelioma
Histology: Most of the lesion consists of a cellular spindle cell lesion with a collagenous appearance. The nuclei are fairly uniform and ovoid with visible nucleoli. Mitotic figures are present yet not frequent. In areas, the lesion dissects through the fat leaving entrapped adipocytes. Within the fat, focal glandular structures were identified. The biphasic nature of this lesion composed of epithelial and spindle cell components is diagnostic of a biphasic malignant mesothelioma. Stains for cytokeratin and calretinin were strongly positive both within the spindle cell component as well as within the tubular structures.
Discussion: In contrast to reactive pleural fibrosis, this lesion lacks a significant inflammatory component. Reactive pleural fibrosis may demonstrate mesothelial hyperplasia consisting of tubules. However, these tubules are seen closer to the pleural surface and associated with inflammation. The histology of cellular fibrous tissue dissecting the adipose tissue would also not be expected in a reactive process. The presence of keratin within the spindle cell component does not distinguish reactive pleural fibrosis from malignant mesothelioma as reactive pleural “fibrosis” results from a proliferation of submesothelial cells that also express keratin. A fibromatosis would have a much more uniform growth appearance consisting of long sweeping fascicles of fibrous tissue. The presence of a glandular component rules out fibromatosis. Epithelioid hemangioendothelioma is a low-grade vascular malignancy that lacks a prominent cellular spindled cell component. Rather, it typically consists of epithelioid appearing cells often with a single cytoplasmic vacuole set in a dense hyalinized fibrotic background. Gland formation is not identified. Epithelioid hemangioendotheliomas can express keratin in addition to vascular markers.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 1: 50-year-old male with a painful skin nodule
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Week 3: Case 1
50-year-old male with a painful skin nodule
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Answer: Glomangioma
Histology: The lesion consists of a well circumscribed small nodule within the subcutaneous adipose tissue. Within the center of the lesion are dilated benign appearing vascular channels. Surrounding these ectatic vessels are nests and cords of extremely bland appearing cells. The cells have scant cytoplasm and small round nuclei without nucleoli, mitoses, or pleomorphism. These cells are typical of those found within glomus tumors. When combined with a more prominent vascular component these lesions are designated as “glomangiomas”.
Discussion: Hemangiomas have similar vessels yet lack the cellular component exterior to the vessels. Paragangliomas, when found near the jugulotympanic region are referred to as “glomus jugulare tumors”, although they are different tumors than glomus tumors. Paragangliomas have a very prominent thin-walled vascular component evenly distributed throughout the lesion as is typical of many endocrine type tumors. In paragangliomas, the cells between the vessels are not as uniform, round and bland as seen within a glomus tumor. Whereas glomus tumors consist of modified smooth muscle cells that stain with actin, paragangliomas are neuroendocrine tumors. Hemangiopericytomas usually lack the dilated vascular component seen in glomangiomas. As in glomus tumors, the cells in hemangiopericytoma lie exterior to the endothelial cells. However, the cells in hemangiopericytoma have a short spindled morphology.
Incorrect
Answer: Glomangioma
Histology: The lesion consists of a well circumscribed small nodule within the subcutaneous adipose tissue. Within the center of the lesion are dilated benign appearing vascular channels. Surrounding these ectatic vessels are nests and cords of extremely bland appearing cells. The cells have scant cytoplasm and small round nuclei without nucleoli, mitoses, or pleomorphism. These cells are typical of those found within glomus tumors. When combined with a more prominent vascular component these lesions are designated as “glomangiomas”.
Discussion: Hemangiomas have similar vessels yet lack the cellular component exterior to the vessels. Paragangliomas, when found near the jugulotympanic region are referred to as “glomus jugulare tumors”, although they are different tumors than glomus tumors. Paragangliomas have a very prominent thin-walled vascular component evenly distributed throughout the lesion as is typical of many endocrine type tumors. In paragangliomas, the cells between the vessels are not as uniform, round and bland as seen within a glomus tumor. Whereas glomus tumors consist of modified smooth muscle cells that stain with actin, paragangliomas are neuroendocrine tumors. Hemangiopericytomas usually lack the dilated vascular component seen in glomangiomas. As in glomus tumors, the cells in hemangiopericytoma lie exterior to the endothelial cells. However, the cells in hemangiopericytoma have a short spindled morphology.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 2: 75-year-old male with lower urinary tract symptoms
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Week 3: Case 2
75-year-old male with lower urinary tract symptoms
Correct
Answer: Remote infarct
Histology: In one of the TUR chips there are widely spaced glands set in a densely fibrotic stroma with some recent hemorrhage. At higher magnification, the glands show squamous differentiation. Some of the glands contain necrotic debris and a neutrophilic infiltrate.
Discussion: Sclerosing adenosis, while having a spindle and glandular component, looks distinctly different than a remote infarct. The glands within sclerosing adenosis either resemble ordinary adenosis or consist of crowded individual single cells resembling high-grade prostate cancer. The spindle cell component is extremely cellular in contrast to the hypocellular fibrotic nature of a remote infarct. Squamous cell carcinoma in addition to showing greater cytologic atypia would have a more infiltrative appearance rather than appearing to show squamous differentiation within a localized nodule. Prostates following the use of hormone therapy may show similar immature squamous metaplasia. However, the squamous metaplasia is present diffusely throughout the gland.
Incorrect
Answer: Remote infarct
Histology: In one of the TUR chips there are widely spaced glands set in a densely fibrotic stroma with some recent hemorrhage. At higher magnification, the glands show squamous differentiation. Some of the glands contain necrotic debris and a neutrophilic infiltrate.
Discussion: Sclerosing adenosis, while having a spindle and glandular component, looks distinctly different than a remote infarct. The glands within sclerosing adenosis either resemble ordinary adenosis or consist of crowded individual single cells resembling high-grade prostate cancer. The spindle cell component is extremely cellular in contrast to the hypocellular fibrotic nature of a remote infarct. Squamous cell carcinoma in addition to showing greater cytologic atypia would have a more infiltrative appearance rather than appearing to show squamous differentiation within a localized nodule. Prostates following the use of hormone therapy may show similar immature squamous metaplasia. However, the squamous metaplasia is present diffusely throughout the gland.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 3: Finding in grossly normal thyroid gland.
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Week 3: Case 3
Finding in grossly normal thyroid gland.
Correct
Answer: C cell hyperplasia
Histology: This case was a prophylactic thyroidectomy performed because of a history of medullary carcinoma within the family. Towards the upper third portion of both lobes, C cell hyperplasia was evident. This is characterized by a proliferation of cells with uniform round nuclei and abundant amphophilic cytoplasm located within some of the follicles, although in some of the planes of sections it is difficult to appreciate that the hyperplastic cells are part of a follicle. More than six C cells per follicle is diagnostic of C cell hyperplasia. These cells strongly express calcitonin immunohistochemically.
Discussion: Solid cell nests which are thought to represent remnants of the ultimobranchial body are small nests composed of oval cells with occasional clear cells. There may be occasional small glandular lumina with mucinous secretion. These lesions lack the relationship to follicles seen with C cell hyperplasia and do not express calcitonin. They also are not preferentially located towards the upper third of the thyroid. It should be recognized that one may see an increased number of C cells around solid cell nests. Medullary carcinomas may have similar cytologic features, yet would be invasive and not restricted to follicles. Papillary microcarcinoma would have the characteristic nuclear features of papillary carcinoma. These would consist of more ovoid, overlapping, irregular nuclei often showing optical clearing, nuclear grooves, and nuclear pseudoinclusions. Papillary microcarcinomas often are associated with sclerosis.
Incorrect
Answer: C cell hyperplasia
Histology: This case was a prophylactic thyroidectomy performed because of a history of medullary carcinoma within the family. Towards the upper third portion of both lobes, C cell hyperplasia was evident. This is characterized by a proliferation of cells with uniform round nuclei and abundant amphophilic cytoplasm located within some of the follicles, although in some of the planes of sections it is difficult to appreciate that the hyperplastic cells are part of a follicle. More than six C cells per follicle is diagnostic of C cell hyperplasia. These cells strongly express calcitonin immunohistochemically.
Discussion: Solid cell nests which are thought to represent remnants of the ultimobranchial body are small nests composed of oval cells with occasional clear cells. There may be occasional small glandular lumina with mucinous secretion. These lesions lack the relationship to follicles seen with C cell hyperplasia and do not express calcitonin. They also are not preferentially located towards the upper third of the thyroid. It should be recognized that one may see an increased number of C cells around solid cell nests. Medullary carcinomas may have similar cytologic features, yet would be invasive and not restricted to follicles. Papillary microcarcinoma would have the characteristic nuclear features of papillary carcinoma. These would consist of more ovoid, overlapping, irregular nuclei often showing optical clearing, nuclear grooves, and nuclear pseudoinclusions. Papillary microcarcinomas often are associated with sclerosis.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 4: Elderly man presented with vague abdominal pain.
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Week 3: Case 4
This elderly man presented with vague abdominal pain. A CT scan revealed a large (10 cm) cystic mass in the tail of the pancreas. The lesion had a honeycomb appearance and a central stellate scar. A distal pancreatectomy was performed.
Correct
Answer: Serous cystadenoma with PanINs
Histology: The lesion is a classic serous cystadenoma. It is composed of innumerable small (1-3 mm) cysts lined by a cuboidal lining. The lining cells have a clear cytoplasm (from glycogen) and centrally placed round uniform nuclei. In addition to the serous cystadenoma, the adjacent pancreas is remarkable for pancreatic intraepithelial neoplasia (PanIN). The PanIN lesions involve the smaller pancreatic ducts and are composed of a papillary epithelium with mild to moderate atypia (PanIN-1 to PanIN-2).
Discussion: Serous cystic neoplasms are virtually always benign and it is therefore important that they are distinguished from mucinous cystic neoplasms and from intraductal papillary mucinous neoplasms. The latter two entities are associated with an invasive carcinoma in a third of the cases. PanINs can occur adjacent to any of these lesions and in this setting PanINs are important to recognize because they can lead to a misdiagnosis on biopsy or fine needle aspiration.
Incorrect
Answer: Serous cystadenoma with PanINs
Histology: The lesion is a classic serous cystadenoma. It is composed of innumerable small (1-3 mm) cysts lined by a cuboidal lining. The lining cells have a clear cytoplasm (from glycogen) and centrally placed round uniform nuclei. In addition to the serous cystadenoma, the adjacent pancreas is remarkable for pancreatic intraepithelial neoplasia (PanIN). The PanIN lesions involve the smaller pancreatic ducts and are composed of a papillary epithelium with mild to moderate atypia (PanIN-1 to PanIN-2).
Discussion: Serous cystic neoplasms are virtually always benign and it is therefore important that they are distinguished from mucinous cystic neoplasms and from intraductal papillary mucinous neoplasms. The latter two entities are associated with an invasive carcinoma in a third of the cases. PanINs can occur adjacent to any of these lesions and in this setting PanINs are important to recognize because they can lead to a misdiagnosis on biopsy or fine needle aspiration.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 5: 87-year-old male with a red cheek mass
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Week 3: Case 5
87-year-old male with a red cheek mass
Correct
Answer: Angiosarcoma
Histology: An increased number of well-formed vessels are visualized within the superficial dermis. These vessels are irregularly shaped and often contain islands of collagen surrounded by endothelium within the center of the vascular lumina. Other vessels have a more interanastomosing appearance. Although the endothelium lining most of these vessels appear bland, in areas endothelial cells have a hobnailed appearance with hyperchromatic nuclei. Abundant hemosiderin deposition is present within the dermis. The dissection around adnexal structures and the presence of little islands of collagen surrounded by hyperchromatic endothelial cells are typical for well-differentiated angiosarcoma. In cases where angiosarcoma has a very bland cytologic appearance, clinical correlation is helpful; this patient’s lesion was extensive with satellite nodules.
Discussion: Telangiectasia would merely show rounded dilated vessels in the dermis without the complex shapes seen in the current case. The lesion would also be restricted to the very superficial dermis and not infiltrate around adnexal structures. Port wine stains and hemangiomas both contain rounded, well-formed vessels lined by bland endothelium. Whereas hemangioma consists of vessels that are closely compacted in a circumscribed nodule, the vessels in port wine stain are more loosely arranged in the dermis and lack circumscription.
Incorrect
Answer: Angiosarcoma
Histology: An increased number of well-formed vessels are visualized within the superficial dermis. These vessels are irregularly shaped and often contain islands of collagen surrounded by endothelium within the center of the vascular lumina. Other vessels have a more interanastomosing appearance. Although the endothelium lining most of these vessels appear bland, in areas endothelial cells have a hobnailed appearance with hyperchromatic nuclei. Abundant hemosiderin deposition is present within the dermis. The dissection around adnexal structures and the presence of little islands of collagen surrounded by hyperchromatic endothelial cells are typical for well-differentiated angiosarcoma. In cases where angiosarcoma has a very bland cytologic appearance, clinical correlation is helpful; this patient’s lesion was extensive with satellite nodules.
Discussion: Telangiectasia would merely show rounded dilated vessels in the dermis without the complex shapes seen in the current case. The lesion would also be restricted to the very superficial dermis and not infiltrate around adnexal structures. Port wine stains and hemangiomas both contain rounded, well-formed vessels lined by bland endothelium. Whereas hemangioma consists of vessels that are closely compacted in a circumscribed nodule, the vessels in port wine stain are more loosely arranged in the dermis and lack circumscription.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 1: 47-year-old female with parotid mass
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Week 2: Case 1
47-year-old female with parotid mass
Correct
Answer: Benign lymphoepithelial cyst
Histology: Within the parotid gland are two cystic structures surrounded by lymphoid tissue containing germinal centers. One nodule resembles a lymph node, whereas in areas the other merges in with the surrounding salivary gland and is less well defined. The lining of the cyst wall consists of squamous epithelium with a heavy infiltrate of benign appearing lymphocytes. Focally, within the lymphoid tissue surrounding one of the cysts are epimyoepithelial islands.
Discussion: Branchial cleft cysts may show a similar appearance with squamous lined cysts surrounded by lymphoid cuffs. Branchial cleft cysts, however, occur in the lateral portion of the neck and do not involve the salivary gland. Warthin’s tumors are also cystic lesions with a lymphoid infiltrate. Their epithelium, however, consists of oncocytic cells. Sjögren’s disease consists of a lymphoid infiltrate with epimyoepithelial islands. The localized nature of the lesion within an otherwise histologically unremarkable salivary gland argues against Sjögren’s disease.
Incorrect
Answer: Benign lymphoepithelial cyst
Histology: Within the parotid gland are two cystic structures surrounded by lymphoid tissue containing germinal centers. One nodule resembles a lymph node, whereas in areas the other merges in with the surrounding salivary gland and is less well defined. The lining of the cyst wall consists of squamous epithelium with a heavy infiltrate of benign appearing lymphocytes. Focally, within the lymphoid tissue surrounding one of the cysts are epimyoepithelial islands.
Discussion: Branchial cleft cysts may show a similar appearance with squamous lined cysts surrounded by lymphoid cuffs. Branchial cleft cysts, however, occur in the lateral portion of the neck and do not involve the salivary gland. Warthin’s tumors are also cystic lesions with a lymphoid infiltrate. Their epithelium, however, consists of oncocytic cells. Sjögren’s disease consists of a lymphoid infiltrate with epimyoepithelial islands. The localized nature of the lesion within an otherwise histologically unremarkable salivary gland argues against Sjögren’s disease.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 2: 14-year-old male with nose bleed
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Week 2: Case 2
14-year-old male with nose bleed
Correct
Answer: Angiofibroma
Histology: The lesion consists of a densely fibrous mass situated beneath the surface squamous mucosa. Fibroblastic cells have a stellate appearance with enlarged nuclei revealing occasional nucleoli and minimal pleomorphism. The lesion is highly vascular with normal appearing endothelial cells line the vascular channels.
Discussion: Hemangiomas lack a densely fibrotic component and fibromas do not have a vascular element. Nasal polyps are composed of loose myxoid stroma and mucous glands covered by respiratory epithelium. They often contain prominent inflammation. Nasal polyps are not neoplasms but rather a polypoid reaction to inflammation and associated edema.
Incorrect
Answer: Angiofibroma
Histology: The lesion consists of a densely fibrous mass situated beneath the surface squamous mucosa. Fibroblastic cells have a stellate appearance with enlarged nuclei revealing occasional nucleoli and minimal pleomorphism. The lesion is highly vascular with normal appearing endothelial cells line the vascular channels.
Discussion: Hemangiomas lack a densely fibrotic component and fibromas do not have a vascular element. Nasal polyps are composed of loose myxoid stroma and mucous glands covered by respiratory epithelium. They often contain prominent inflammation. Nasal polyps are not neoplasms but rather a polypoid reaction to inflammation and associated edema.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 3: Lower back pain in a 13-year-old female
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Week 2: Case 3
Lower back pain in a 13-year-old female
Correct
Answer: Myxopapillary ependymoma
Histology: Within a background of cells with ovoid nuclei and slight cytoplasmic processes are rounded myxoid pools. In some planes of sections, one can appreciate within the center of these myxoid pools a fibrovascular core. In the best developed regions of this lesion, nuclei palisade around and send elongated processes towards the fibrovascular core.
Discussion: A more fibrillary neuropil matrix characterizes the other entities listed as diagnostic choices. The only lesion listed in the differential diagnosis that has a myxoid appearance is pilocytic astrocytoma. In pilocytic astrocytomas, the myxoid pools are not circumscribed rounded structures with central fibrovascular cores, but rather represent myxoid degeneration within a glial background of astrocytic cells with long fibrillary processes.
Incorrect
Answer: Myxopapillary ependymoma
Histology: Within a background of cells with ovoid nuclei and slight cytoplasmic processes are rounded myxoid pools. In some planes of sections, one can appreciate within the center of these myxoid pools a fibrovascular core. In the best developed regions of this lesion, nuclei palisade around and send elongated processes towards the fibrovascular core.
Discussion: A more fibrillary neuropil matrix characterizes the other entities listed as diagnostic choices. The only lesion listed in the differential diagnosis that has a myxoid appearance is pilocytic astrocytoma. In pilocytic astrocytomas, the myxoid pools are not circumscribed rounded structures with central fibrovascular cores, but rather represent myxoid degeneration within a glial background of astrocytic cells with long fibrillary processes.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 4: 71-year-old male with knee pain
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Week 2: Case 4
71-year-old male with knee pain
Correct
Answer: Chondrocalcinosis
Histology: Polypoid fragments of dense fibrous tissue lined by synovium contain intensely basophilic irregular deposits of calcification. At higher magnification within the basophilic regions, there are numerous needle-shaped crystalline structures, which can be highlighted when polarized. Another name for chondrocalcinosis is pseudogout.
Discussion: When fixed in formalin, gout appears as amorphous lightly eosinophilic material which elicits a prominent multinucleated giant cell reaction. Calcification may occur within gout secondarily. If tissues involved by gout are fixed in absolute ethanol, sharply demarcated aggregates of needle shaped urate crystals lying in bundles can be visualized. Ochronosis when stained with H&E has a distinctive yellow-brown color; the pigment is deposited within collagen bundles, which often fragment and degenerate forming clumps. It does not elicit a foreign body giant cell reaction. Dystrophic calcification lacks crystalline structures.
Incorrect
Answer: Chondrocalcinosis
Histology: Polypoid fragments of dense fibrous tissue lined by synovium contain intensely basophilic irregular deposits of calcification. At higher magnification within the basophilic regions, there are numerous needle-shaped crystalline structures, which can be highlighted when polarized. Another name for chondrocalcinosis is pseudogout.
Discussion: When fixed in formalin, gout appears as amorphous lightly eosinophilic material which elicits a prominent multinucleated giant cell reaction. Calcification may occur within gout secondarily. If tissues involved by gout are fixed in absolute ethanol, sharply demarcated aggregates of needle shaped urate crystals lying in bundles can be visualized. Ochronosis when stained with H&E has a distinctive yellow-brown color; the pigment is deposited within collagen bundles, which often fragment and degenerate forming clumps. It does not elicit a foreign body giant cell reaction. Dystrophic calcification lacks crystalline structures.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 5: 40-year-old male with a tumor involving the skull
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Week 2: Case 5
40-year-old male with a tumor involving the skull
Correct
Answer: Chordoma
Histology: Within dense fibrous tissue are myxoid nodules containing cords of tumor cells. At higher magnification, most of the tumor cells have a relatively uniform monotonous appearance with infrequent mitoses. Some of the cells have very prominent vacuolated cytoplasm resembling lipoblasts. These cells are known as “physaliferous cells”. Focally, cells show a somewhat greater degree of cytologic atypia, which may be seen in recurrent chordomas or those that have been treated with radiation.
Discussion: The location of the tumor within the skull would be helpful to know as chordoma arising in the skull classically occurs at the clivus. In some cases, it may be difficult to distinguish a myxoid chondrosarcoma from a chordoma; immunohistochemical demonstration of keratin is diagnostic of a chordoma. Chondroma has distinct cartilage formation, rather than merely a myxoid matrix. Metastatic mucinous adenocarcinomas can also bear a resemblance to chordoma. However, in this case, the presence of physaliferous cells rules out other entities.
Incorrect
Answer: Chordoma
Histology: Within dense fibrous tissue are myxoid nodules containing cords of tumor cells. At higher magnification, most of the tumor cells have a relatively uniform monotonous appearance with infrequent mitoses. Some of the cells have very prominent vacuolated cytoplasm resembling lipoblasts. These cells are known as “physaliferous cells”. Focally, cells show a somewhat greater degree of cytologic atypia, which may be seen in recurrent chordomas or those that have been treated with radiation.
Discussion: The location of the tumor within the skull would be helpful to know as chordoma arising in the skull classically occurs at the clivus. In some cases, it may be difficult to distinguish a myxoid chondrosarcoma from a chordoma; immunohistochemical demonstration of keratin is diagnostic of a chordoma. Chondroma has distinct cartilage formation, rather than merely a myxoid matrix. Metastatic mucinous adenocarcinomas can also bear a resemblance to chordoma. However, in this case, the presence of physaliferous cells rules out other entities.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 6: 43-year-old male with a lesion involving the skull
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Week 2: Case 6
43-year-old male with a lesion involving the skull
Correct
Answer: Plasmacytoma
Histology: The lesion consists of sheets of a monotonous population of loosely cohesive cells. The nuclei appear fairly uniform and round. The chromatin either has a speckled appearance or small nucleoli are visible. The cytoplasm appears eccentric, with in some areas a paranuclear hof typical of plasma cell differentiation. Focally, there is a greater degree of cytologic atypia.
Discussion: Pituitary adenomas may also have a very plasmacytoid appearance, although the current case shows unequivocal plasma cell differentiation. Location of the tumor and immunohistochemical stains for light chains can help distinguish these two entities. Although immunoblastic lymphomas demonstrate plasmacytoid differentiation, its histology is that of a large cell lymphoma with plasmacytoid features, whereas case 6 demonstrates a predominance of mature plasma cells with focal atypia. Metastatic carcinoma should always be considered in a lesion involving the skull, although the histological features in this case are quite typical of a plasma cell lesion. Immunohistochemical stains for cytokeratin and light chains readily differentiate these two lesions.
Incorrect
Answer: Plasmacytoma
Histology: The lesion consists of sheets of a monotonous population of loosely cohesive cells. The nuclei appear fairly uniform and round. The chromatin either has a speckled appearance or small nucleoli are visible. The cytoplasm appears eccentric, with in some areas a paranuclear hof typical of plasma cell differentiation. Focally, there is a greater degree of cytologic atypia.
Discussion: Pituitary adenomas may also have a very plasmacytoid appearance, although the current case shows unequivocal plasma cell differentiation. Location of the tumor and immunohistochemical stains for light chains can help distinguish these two entities. Although immunoblastic lymphomas demonstrate plasmacytoid differentiation, its histology is that of a large cell lymphoma with plasmacytoid features, whereas case 6 demonstrates a predominance of mature plasma cells with focal atypia. Metastatic carcinoma should always be considered in a lesion involving the skull, although the histological features in this case are quite typical of a plasma cell lesion. Immunohistochemical stains for cytokeratin and light chains readily differentiate these two lesions.
Presented by Jonathan Epstein, M.D. and prepared by Angelique W. Levi, M.D.
Case 1: 39 year old female with hypokalemia and a 2.5 cm. (9 gram) adrenal mass.
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Week 9: Case 1
39 year old female with hypokalemia and a 2.5 cm. (9 gram) adrenal mass.
Correct
Answer: Adrenal cortical adenoma (Conn’s syndrome with hyperaldosteronemia)
Histology: There is a single nodule arising within the adrenal gland. The lesion is well circumscribed and lacks necrosis. The lesion consists of nests of cells with abundant xanthomatous pale cytoplasm. Nuclei are uniform with visible nucleoli. Mitotic figures are not easily identifiable. Separating the nests is a thin uniform vascular pattern. The surrounding adrenal gland is histologically unremarkable without any other nodularity.
Discussion: Distinction of adrenal cortical adenoma from carcinoma may be difficult in well differentiated cases. Tumors weighing more than 100 grams in adults are typically malignant. Necrosis >2 high power fields and broad fibrous bands are also useful histological signs of carcinoma. High nuclear grade, mitoses (>1 per 10 high power field), atypical mitoses, diffuse growth, vascular/capsular invasion, clear cells <25% of tumor are also good discriminates. Nodular hyperplasia consists of multiple nodules of cortical cells with intervening atrophic cortical tissue. Pheochromocytoma characteristically has very amphophilic granular cytoplasm rather than the pale to clear xanthomatous cytoplasm seen in adrenal cortical lesions.
Incorrect
Answer: Adrenal cortical adenoma (Conn’s syndrome with hyperaldosteronemia)
Histology: There is a single nodule arising within the adrenal gland. The lesion is well circumscribed and lacks necrosis. The lesion consists of nests of cells with abundant xanthomatous pale cytoplasm. Nuclei are uniform with visible nucleoli. Mitotic figures are not easily identifiable. Separating the nests is a thin uniform vascular pattern. The surrounding adrenal gland is histologically unremarkable without any other nodularity.
Discussion: Distinction of adrenal cortical adenoma from carcinoma may be difficult in well differentiated cases. Tumors weighing more than 100 grams in adults are typically malignant. Necrosis >2 high power fields and broad fibrous bands are also useful histological signs of carcinoma. High nuclear grade, mitoses (>1 per 10 high power field), atypical mitoses, diffuse growth, vascular/capsular invasion, clear cells <25% of tumor are also good discriminates. Nodular hyperplasia consists of multiple nodules of cortical cells with intervening atrophic cortical tissue. Pheochromocytoma characteristically has very amphophilic granular cytoplasm rather than the pale to clear xanthomatous cytoplasm seen in adrenal cortical lesions.
Presented by Jonathan Epstein, M.D. and prepared by Angelique W. Levi, M.D.
Case 5: Axillary lymph nodes in a 52 year old male
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Week 9: Case 5
Axillary lymph nodes in a 52 year old male
Correct
Answer: Capsular blue nevus
Histology: Within the capsule of the lymph node are heavily pigmented spindled cells. The pigment is fine, dusty, and brown typical of melanin. The spindled morphology of the cells with long tapering dendritic processes is typical of a blue nevus.
Discussion: Nevocellular aggregates also represent nevus cells within the capsule of the lymph node. Nevocellular aggregates typically are non-pigmented and consist of benign nevus cells similar to what is seen within an intradermal nevus. Metastatic melanoma would not consist of dendritic pigmented cells and would be present within the sinuses rather than the capsule of the lymph node. A greater degree of cytologic atypia would also be expected. Hemosiderin deposition within the lymph node would have a different morphology consisting of a more clumped refractile, granular, orange pigment. Hemosiderin deposition would also be present within histiocytes rather than in spindled dendritic cells.
Incorrect
Answer: Capsular blue nevus
Histology: Within the capsule of the lymph node are heavily pigmented spindled cells. The pigment is fine, dusty, and brown typical of melanin. The spindled morphology of the cells with long tapering dendritic processes is typical of a blue nevus.
Discussion: Nevocellular aggregates also represent nevus cells within the capsule of the lymph node. Nevocellular aggregates typically are non-pigmented and consist of benign nevus cells similar to what is seen within an intradermal nevus. Metastatic melanoma would not consist of dendritic pigmented cells and would be present within the sinuses rather than the capsule of the lymph node. A greater degree of cytologic atypia would also be expected. Hemosiderin deposition within the lymph node would have a different morphology consisting of a more clumped refractile, granular, orange pigment. Hemosiderin deposition would also be present within histiocytes rather than in spindled dendritic cells.
Presented by Jonathan Epstein, M.D. and prepared by Angelique W. Levi, M.D.
Case 2: 38 year old female with a 17 cm (1070 gram adrenal mass)
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Week 9: Case 2
38 year old female with a 17 cm (1070 gram adrenal mass)
Correct
Answer:
Histology: The lesion is a pink cell tumor with diffuse sheets of cells with abundant eosinophilic cytoplasm. Some morphology ranges from uniform bland cells with small round nuclei to cells with marked pleomorphism. Mitotic figures including atypical ones are readily identifiable. There is necrosis identified. The large size, extensive pleomorphism, necrosis and atypical mitotic figures are all diagnostic of adrenal cortical carcinoma.
Discussion: The distinction of adrenal cortical adenoma and adrenal cortical carcinoma and pheochromocytoma is described above in case 1. Metastatic carcinoma to the adrenal is not uncommon especially from the lung. In this case, the cellular morphology closely resembles adrenal cortical cells, such that adrenal cortical carcinoma is favored over melanoma. Adrenal cortical carcinomas are positive for vimentin and variably positive for keratin, which could also rule out melanoma.
Incorrect
Answer:
Histology: The lesion is a pink cell tumor with diffuse sheets of cells with abundant eosinophilic cytoplasm. Some morphology ranges from uniform bland cells with small round nuclei to cells with marked pleomorphism. Mitotic figures including atypical ones are readily identifiable. There is necrosis identified. The large size, extensive pleomorphism, necrosis and atypical mitotic figures are all diagnostic of adrenal cortical carcinoma.
Discussion: The distinction of adrenal cortical adenoma and adrenal cortical carcinoma and pheochromocytoma is described above in case 1. Metastatic carcinoma to the adrenal is not uncommon especially from the lung. In this case, the cellular morphology closely resembles adrenal cortical cells, such that adrenal cortical carcinoma is favored over melanoma. Adrenal cortical carcinomas are positive for vimentin and variably positive for keratin, which could also rule out melanoma.
Presented by Jonathan Epstein, M.D. and prepared by Angelique W. Levi, M.D.
Case 3: 47 year old female with a breast mass
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Week 9: Case 3
47 year old female with a breast mass
Correct
Answer: Metaplastic carcinoma
Histology: The lesion has a biphasic component. In areas the lesion resembles a classic infiltrating poorly differentiated duct carcinoma with nests and cords of malignant appearing epithelial cells. Elsewhere, the lesion has a distinct chondroid appearance. The chondroid areas merge imperceptibly with the epithelial areas. The cells within the chondroid appearance have similar malignant features to that of the surrounding infiltrating carcinoma. The presence of both a malignant cartilagenous and epithelial component is diagnostic of metaplastic carcinoma. Metaplastic carcinoma is a general term for breast carcinomas in which there is an additional component other than epithelial and glandular. In this case, with both epithelial and malignant spindle cell features this lesion would be regarded as a sarcomatoid carcinoma. Some individuals make the distinction between sarcomatoid carcinoma where the epithelial and spindle cell carcinoma merges with each other in contrast to “carcinosarcoma” where the two components are distinct. However, there is overlap between the two both histologically and immunohistochemically, and prognostically there is no difference. Consequently, we regard both sarcomatoid carcinoma (carcinoma with spindle cell differentiation) and carcinosarcoma as the same entity.
Discussion: The presence of an epithelial component typical of infiltrating duct carcinoma rules out a pure chondrosarcoma. Malignant phyllodes tumor has a malignant mesenchymal component yet the epithelium appears benign. In carcinoma with chondroid metaplasia, the cartilage would have a totally benign appearance and would not merge in with the carcinoma.
Incorrect
Answer: Metaplastic carcinoma
Histology: The lesion has a biphasic component. In areas the lesion resembles a classic infiltrating poorly differentiated duct carcinoma with nests and cords of malignant appearing epithelial cells. Elsewhere, the lesion has a distinct chondroid appearance. The chondroid areas merge imperceptibly with the epithelial areas. The cells within the chondroid appearance have similar malignant features to that of the surrounding infiltrating carcinoma. The presence of both a malignant cartilagenous and epithelial component is diagnostic of metaplastic carcinoma. Metaplastic carcinoma is a general term for breast carcinomas in which there is an additional component other than epithelial and glandular. In this case, with both epithelial and malignant spindle cell features this lesion would be regarded as a sarcomatoid carcinoma. Some individuals make the distinction between sarcomatoid carcinoma where the epithelial and spindle cell carcinoma merges with each other in contrast to “carcinosarcoma” where the two components are distinct. However, there is overlap between the two both histologically and immunohistochemically, and prognostically there is no difference. Consequently, we regard both sarcomatoid carcinoma (carcinoma with spindle cell differentiation) and carcinosarcoma as the same entity.
Discussion: The presence of an epithelial component typical of infiltrating duct carcinoma rules out a pure chondrosarcoma. Malignant phyllodes tumor has a malignant mesenchymal component yet the epithelium appears benign. In carcinoma with chondroid metaplasia, the cartilage would have a totally benign appearance and would not merge in with the carcinoma.
Presented by Jonathan Epstein, M.D. and prepared by Angelique W. Levi, M.D.
Case 4: 65 year old male with an intradural mass C2-4
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Week 9: Case 4
65 year old male with an intradural mass C2-4
Correct
Answer: Hemangioblastoma
Histology: The lesion is vascular with numerous thin-walled vessels evenly distributed throughout. The vessels appear unremarkable with normal appearing endothelial cells. In between the vessels is a proliferation of short spindle and ovoid cells with pale to clear vacuolated cytoplasm. The lesion lacks significant pleomorphism. Mitotic figures are not identified. The nuclei show some variation in size and shape and minimal nuclear irregularity. Prominent nucleoli are not identified.
Discussion: Hemangiopericytomas share the vascular pattern seen in hemangioblastomas with the exception that some hemangiopericytomas have more dilated and branching vessels (staghorn vessels). In hemangiopericytomas, the cells between the vessels have a more spindled component and do not have the vacuolated clear cytoplasm seen within hemangioblastoma. Hemangiomas lack the intervening foamy cells seen in hemangioblastoma. Metastatic renal cell carcinoma may bear a close resemblance to hemangioblastoma. Furthermore, in patients with von Hippel Lindau syndrome, patients are at increased risk of both hemangioblastoma and renal cell carcinoma. In the current case, the cells between the vessels have a more lipidized appearance than typically seen in renal cell carcinoma. Also, in renal cell carcinomas with more prominent cytologic atypia, prominent nucleoli tend to be visible. In cases where the distinction can not be made with certainty on H&E stain, immunohistochemical stains for epithelial membrane antigen may be helpful where they are negative in hemangioblastoma and positive in renal cell carcinoma.
Incorrect
Answer: Hemangioblastoma
Histology: The lesion is vascular with numerous thin-walled vessels evenly distributed throughout. The vessels appear unremarkable with normal appearing endothelial cells. In between the vessels is a proliferation of short spindle and ovoid cells with pale to clear vacuolated cytoplasm. The lesion lacks significant pleomorphism. Mitotic figures are not identified. The nuclei show some variation in size and shape and minimal nuclear irregularity. Prominent nucleoli are not identified.
Discussion: Hemangiopericytomas share the vascular pattern seen in hemangioblastomas with the exception that some hemangiopericytomas have more dilated and branching vessels (staghorn vessels). In hemangiopericytomas, the cells between the vessels have a more spindled component and do not have the vacuolated clear cytoplasm seen within hemangioblastoma. Hemangiomas lack the intervening foamy cells seen in hemangioblastoma. Metastatic renal cell carcinoma may bear a close resemblance to hemangioblastoma. Furthermore, in patients with von Hippel Lindau syndrome, patients are at increased risk of both hemangioblastoma and renal cell carcinoma. In the current case, the cells between the vessels have a more lipidized appearance than typically seen in renal cell carcinoma. Also, in renal cell carcinomas with more prominent cytologic atypia, prominent nucleoli tend to be visible. In cases where the distinction can not be made with certainty on H&E stain, immunohistochemical stains for epithelial membrane antigen may be helpful where they are negative in hemangioblastoma and positive in renal cell carcinoma.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 1: 51-year-old female with a breast mass
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Category: breast
Week 1: Case 1
This is a 51-year-old female with a breast mass.
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Answer: Small cell carcinoma
Histology: This is a high grade malignant neoplasm composed of cells with high nucleus to cytoplasm ratio arranged in nests and sheets, involving the mammary stroma. These cells show predominant features of small cell carcinoma; that is, they have hyperchromatic nuclei which mold to each other and lack prominent nucleoli. These areas label for neuroendocrine markers like CD56, and demonstrate dot-like cytokeratin immunoreactivity. Very focally, one can appreciate an area in which the cells have more open, vesicular chromatin, typical of ductal carcinoma of the breast. This area lacks labeling for neuroendocrine markers.
Discussion: Basal-like carcinoma would label for high molecular cytokeratin and not for neuroendocrine markers, and typically would demonstrate a more nested architecture with peripheral palisading with central necrosis. Malignant lymphoma would be less cohesive, and would label for lymphoid markers but not cytokeratin. Desmoplastic small round cell tumor typically occurs in younger patients, and would demonstrate immunoreactivity for desmin in addition to cytokeratin.
The presence of a focal typical mammary component or ductal carcinoma in situ helps assure that a small cell carcinoma involving the breast is primary to this site.
Reference: American Journal of Surgical Pathology 2000; 24:1231-8.
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Answer: Small cell carcinoma
Histology: This is a high grade malignant neoplasm composed of cells with high nucleus to cytoplasm ratio arranged in nests and sheets, involving the mammary stroma. These cells show predominant features of small cell carcinoma; that is, they have hyperchromatic nuclei which mold to each other and lack prominent nucleoli. These areas label for neuroendocrine markers like CD56, and demonstrate dot-like cytokeratin immunoreactivity. Very focally, one can appreciate an area in which the cells have more open, vesicular chromatin, typical of ductal carcinoma of the breast. This area lacks labeling for neuroendocrine markers.
Discussion: Basal-like carcinoma would label for high molecular cytokeratin and not for neuroendocrine markers, and typically would demonstrate a more nested architecture with peripheral palisading with central necrosis. Malignant lymphoma would be less cohesive, and would label for lymphoid markers but not cytokeratin. Desmoplastic small round cell tumor typically occurs in younger patients, and would demonstrate immunoreactivity for desmin in addition to cytokeratin.
The presence of a focal typical mammary component or ductal carcinoma in situ helps assure that a small cell carcinoma involving the breast is primary to this site.
Reference: American Journal of Surgical Pathology 2000; 24:1231-8.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 2: 46-year-old female with a skin nodule
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Week 1: Case 2
46-year-old female with a skin nodule
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Answer: Langerhans cell histiocytosis
Histology: The lesion is characterized by a dense dermal infiltrate, which is fairly small and symmetrical and lacks epidermal involvement. The infiltrate is composed of larger cells with irregular nuclei, some of which show nuclear grooves. Despite the large size of the nuclei and scattered mitotic figures, nucleoli are not prominent. There is also a second population of small benign appearing mature lymphocytes. Other cell types, such as eosinophils and multinucleated histiocytes, are present though not numerous. Immunohistochemical stains for CD1A were strongly positive in the large cells consistent with Langerhans’ cell histiocytosis.
Discussion: On purely morphologic grounds, it may be difficult to exclude a lymphoma and one would need marker studies to characterize the large cells more completely. Arguing against lymphoma would be the difficulty in its classification. The large cells would suggest a diagnosis of large cell lymphoma. However, the presence of a population of small round mature lymphocytes would be somewhat unusual for this diagnosis, as would the lack of more prominent nucleoli. Against the diagnosis of malignant melanoma are the lack of epidermal involvement, the lack of prominent nucleoli, and the presence of scattered benign appearing multinucleated giant cells. The relatively small size, circumscription, and symmetry of the lesion also argue against melanoma. Lymphocytoma cutis consists of a mixture of benign appearing histiocytes and small normal appearing lymphocytes. The larger cells in this case do not have the appearance of normal looking histiocytes. Rather, many if them are cytologically atypical with irregular nuclear contours and occasional folds.
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Answer: Langerhans cell histiocytosis
Histology: The lesion is characterized by a dense dermal infiltrate, which is fairly small and symmetrical and lacks epidermal involvement. The infiltrate is composed of larger cells with irregular nuclei, some of which show nuclear grooves. Despite the large size of the nuclei and scattered mitotic figures, nucleoli are not prominent. There is also a second population of small benign appearing mature lymphocytes. Other cell types, such as eosinophils and multinucleated histiocytes, are present though not numerous. Immunohistochemical stains for CD1A were strongly positive in the large cells consistent with Langerhans’ cell histiocytosis.
Discussion: On purely morphologic grounds, it may be difficult to exclude a lymphoma and one would need marker studies to characterize the large cells more completely. Arguing against lymphoma would be the difficulty in its classification. The large cells would suggest a diagnosis of large cell lymphoma. However, the presence of a population of small round mature lymphocytes would be somewhat unusual for this diagnosis, as would the lack of more prominent nucleoli. Against the diagnosis of malignant melanoma are the lack of epidermal involvement, the lack of prominent nucleoli, and the presence of scattered benign appearing multinucleated giant cells. The relatively small size, circumscription, and symmetry of the lesion also argue against melanoma. Lymphocytoma cutis consists of a mixture of benign appearing histiocytes and small normal appearing lymphocytes. The larger cells in this case do not have the appearance of normal looking histiocytes. Rather, many if them are cytologically atypical with irregular nuclear contours and occasional folds.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 3: 64 year old male had a history of radical nephrectomy for non-invasive papillary urothelial carcinoma
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Week 1: Case 3
A 64 year old male had a history of radical nephrectomy for non-invasive papillary urothelial carcinoma. The patient had also a history of bladder catheterization and now presents with multiple bladder lesions.
Correct
Answer: Inverted papilloma with carcinoma in-situ
Histology: The urothelium is of normal thickness with uniform bland cytology. There are numerous eosinophils in the urothelium as well as in the lamina propria. A dense lymphocytic infiltrate is also present in the lamina propria. No parasites are noted.
Discussion: Rarely numerous eosinophils may be seen in the bladder as part of a systemic allergic reaction. In order to diagnose allergic cystitis, there should be a history of systemic allergy such as asthma or a severely atopic individual. Usually, allergic cystitis would be accompanied by increased eosinophils in the peripheral blood. In these cases, the patients may be treated with steroids. Another setting with increased eosinophils in the bladder is with parasites. The most common situation is with Schistosomiasis seen typically in patients from Africa or with travel to this region. In these cases, the parasites are usually readily identifiable. More commonly the presence of eosinophils is merely a component of reactive subacute inflammation, such as may be seen surrounding a recent TUR site or other areas relating to injury. In the current case, it most likely arose as a response to the catheter. In cases without a specific etiology, they should be diagnosed descriptively as eosinophilic cystitis with a list of the potential etiologies with clinicopathological correlation needed.
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Answer: Inverted papilloma with carcinoma in-situ
Histology: The urothelium is of normal thickness with uniform bland cytology. There are numerous eosinophils in the urothelium as well as in the lamina propria. A dense lymphocytic infiltrate is also present in the lamina propria. No parasites are noted.
Discussion: Rarely numerous eosinophils may be seen in the bladder as part of a systemic allergic reaction. In order to diagnose allergic cystitis, there should be a history of systemic allergy such as asthma or a severely atopic individual. Usually, allergic cystitis would be accompanied by increased eosinophils in the peripheral blood. In these cases, the patients may be treated with steroids. Another setting with increased eosinophils in the bladder is with parasites. The most common situation is with Schistosomiasis seen typically in patients from Africa or with travel to this region. In these cases, the parasites are usually readily identifiable. More commonly the presence of eosinophils is merely a component of reactive subacute inflammation, such as may be seen surrounding a recent TUR site or other areas relating to injury. In the current case, it most likely arose as a response to the catheter. In cases without a specific etiology, they should be diagnosed descriptively as eosinophilic cystitis with a list of the potential etiologies with clinicopathological correlation needed.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 4: 71-year-old male with an ankle mass
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Week 1: Case 4
71-year-old male with an ankle mass
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Answer: Kaposi’s sarcoma
Histology: A large nodule both in the superficial and deep dermis is present without involvement of the overlying epidermis. Even at low magnification, the lesion shows a hemorrhagic component. At higher magnification, the spindle cells lack significant pleomorphism although scattered mitotic activity is evident. Intercalated between the spindle cells are red blood cells, which in areas has the appearance of cords of cells situated within slit-like spaces. The surrounding connective tissue contains hemosiderin deposition. These findings are classic for Kaposi’s sarcoma.
Discussion: Angiosarcoma rarely has a prominent spindle cell pattern. Rather, epithelioid appearing cells line better developed interanastomosing vascular channels. Nodular fasciitis is a spindle cell proliferation, which also reveals extravasated red blood cells. Nodular fasciitis is a deeper seated lesion, and would not be found in the superficial dermis. Furthermore, nodular fasciitis in its early more cellular phase has a looser arrangement of cells in a more myxoid background. The cells in nodular fasciitis resemble tissue culture-like fibroblasts with uniformly enlarged nuclei containing prominent nucleoli. In less myxoid older lesions of nodular fasciitis, the lesion is much more fibrous. Malignant melanoma may have a prominent spindle cell component, although there is usually some epidermal involvement. Often the spindle cells have more cytologic atypia consisting of large nuclei containing eosinophilic prominent nucleoli. In this case, the presence of extravasated red blood cells and red blood cells in slit-like channels between spindle cells are pathognomic for Kaposi’s sarcoma.
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Answer: Kaposi’s sarcoma
Histology: A large nodule both in the superficial and deep dermis is present without involvement of the overlying epidermis. Even at low magnification, the lesion shows a hemorrhagic component. At higher magnification, the spindle cells lack significant pleomorphism although scattered mitotic activity is evident. Intercalated between the spindle cells are red blood cells, which in areas has the appearance of cords of cells situated within slit-like spaces. The surrounding connective tissue contains hemosiderin deposition. These findings are classic for Kaposi’s sarcoma.
Discussion: Angiosarcoma rarely has a prominent spindle cell pattern. Rather, epithelioid appearing cells line better developed interanastomosing vascular channels. Nodular fasciitis is a spindle cell proliferation, which also reveals extravasated red blood cells. Nodular fasciitis is a deeper seated lesion, and would not be found in the superficial dermis. Furthermore, nodular fasciitis in its early more cellular phase has a looser arrangement of cells in a more myxoid background. The cells in nodular fasciitis resemble tissue culture-like fibroblasts with uniformly enlarged nuclei containing prominent nucleoli. In less myxoid older lesions of nodular fasciitis, the lesion is much more fibrous. Malignant melanoma may have a prominent spindle cell component, although there is usually some epidermal involvement. Often the spindle cells have more cytologic atypia consisting of large nuclei containing eosinophilic prominent nucleoli. In this case, the presence of extravasated red blood cells and red blood cells in slit-like channels between spindle cells are pathognomic for Kaposi’s sarcoma.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 6: 76-year-old male with lymphadenopathy
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Week 1: Case 6
76-year-old male with lymphadenopathy
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Answer: Small lymphocytic lymphoma
Histology: The overall lymph node architecture is effaced. At low power, there are vague areas of nodularity characterized by paler regions. However, well-defined nodules as seen in follicular lymphomas are lacking. At higher magnification, the cells in these paler regions appear round and uniform. These cells are minimally enlarged with more prominent nucleoli than the surrounding dark small mature round lymphocytes. The cells within these pale islands appear to have somewhat more cytoplasm leading to a greater degree of separation compared to the densely packed lymphocytes in the background. These small pale areas are known as pseudofollicular growth centers and are diagnostic of small lymphocytic lymphoma.
Discussion: The follicles in a follicular small cleaved lymphoma are much more well developed than pseudofollicular growth centers. Furthermore, the cells within a follicular small cleaved lymphoma exhibit a greater degree of nuclear irregularity. Small lymphocytic lymphoma coexpresses B and T cell markers, where the cells would be positive for CD20 (B cell marker) as well as CD5 (T cell marker) and/or CD43 (T cell marker). Rather than forming small pale nodules scattered throughout the lesion, large cell lymphoma appears as a distinct irregular nodule of large cells arising within a background of small mature lymphocytes. In large cell lymphoma, the large cells are much more atypical, mitotically active, and sheet-like in contrast to the cells in pseudofollicular growth centers. Mantle lymphoma lacks pseudofollicular growth centers and shows nuclear irregularity intermediate between follicular small cleaved lymphoma and a small lymphocytic lymphoma. Both mantle cell lymphoma and small lymphocytic lymphoma coexpress B and T cell markers, however, only mantle cell lymphomas express cyclin D1.
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Answer: Small lymphocytic lymphoma
Histology: The overall lymph node architecture is effaced. At low power, there are vague areas of nodularity characterized by paler regions. However, well-defined nodules as seen in follicular lymphomas are lacking. At higher magnification, the cells in these paler regions appear round and uniform. These cells are minimally enlarged with more prominent nucleoli than the surrounding dark small mature round lymphocytes. The cells within these pale islands appear to have somewhat more cytoplasm leading to a greater degree of separation compared to the densely packed lymphocytes in the background. These small pale areas are known as pseudofollicular growth centers and are diagnostic of small lymphocytic lymphoma.
Discussion: The follicles in a follicular small cleaved lymphoma are much more well developed than pseudofollicular growth centers. Furthermore, the cells within a follicular small cleaved lymphoma exhibit a greater degree of nuclear irregularity. Small lymphocytic lymphoma coexpresses B and T cell markers, where the cells would be positive for CD20 (B cell marker) as well as CD5 (T cell marker) and/or CD43 (T cell marker). Rather than forming small pale nodules scattered throughout the lesion, large cell lymphoma appears as a distinct irregular nodule of large cells arising within a background of small mature lymphocytes. In large cell lymphoma, the large cells are much more atypical, mitotically active, and sheet-like in contrast to the cells in pseudofollicular growth centers. Mantle lymphoma lacks pseudofollicular growth centers and shows nuclear irregularity intermediate between follicular small cleaved lymphoma and a small lymphocytic lymphoma. Both mantle cell lymphoma and small lymphocytic lymphoma coexpress B and T cell markers, however, only mantle cell lymphomas express cyclin D1.
Presented by Jonathan Epstein, M.D. and prepared by Jospeh Kronz, M.D.
Case 5: 49-year-old male with a cerebellar mass
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Week 1: Case 5
49-year-old male with a cerebellar mass
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Answer: Pilocytic astrocytoma
Histology: A biphasic appearance is evident with more cellular areas alternating with myxoid microcysts. In the more cellular areas, the cells appear to have long processes in a densely fibrillar matrix. In areas there are densely eosinophilic hyaline globular bodies as well as densely eosinophilic rod-like structures, the latter termed “Rosenthal fibers”.
Discussion: The histological findings seen in this case are classic for pilocytic astrocytoma, and do not closely resemble any other entity. The lesion is too cellular for reactive gliosis, although one should recognize that Rosenthal fibers may also be seen in longstanding reactive gliosis adjacent to benign lesions. Pilocytic astrocytomas may show cytologic atypia and vascular proliferation, although it is not seen in the current case, and should not be over diagnosed as an anaplastic astrocytoma. Subependymal giant cell astrocytomas are composed of huge cells with abundant eosinophilic glassy or hyaline cytoplasm, resembling ganglion cells.
Incorrect
Answer: Pilocytic astrocytoma
Histology: A biphasic appearance is evident with more cellular areas alternating with myxoid microcysts. In the more cellular areas, the cells appear to have long processes in a densely fibrillar matrix. In areas there are densely eosinophilic hyaline globular bodies as well as densely eosinophilic rod-like structures, the latter termed “Rosenthal fibers”.
Discussion: The histological findings seen in this case are classic for pilocytic astrocytoma, and do not closely resemble any other entity. The lesion is too cellular for reactive gliosis, although one should recognize that Rosenthal fibers may also be seen in longstanding reactive gliosis adjacent to benign lesions. Pilocytic astrocytomas may show cytologic atypia and vascular proliferation, although it is not seen in the current case, and should not be over diagnosed as an anaplastic astrocytoma. Subependymal giant cell astrocytomas are composed of huge cells with abundant eosinophilic glassy or hyaline cytoplasm, resembling ganglion cells.
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