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Presented by Pedram Argani, M.D. and prepared by Ali Ansari-Lari, M.D.,Ph.D.
Case 1: A 60-year old male status post resection of a squamous cell carcinoma of the tongue one year ago, now with a pulmonary nodule.
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1. Question
Week 114: Case 1
A 60-year old male status post resection of a squamous cell carcinoma of the tongue one year ago, now with a pulmonary nodule./images/arg1a.JPG
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/images/arg1e.JPGCorrect
Answer: Large cell neuroendocrine carcinoma
Histology: The tumor features large geographic areas of necrosis, and is composed of polygonal tumor cells with a high mitotic rate (greater than 1/high power field). The architecture of the tumor is nested, with peripheral palisading and occasional rosette formation. The chromatin is fine and “salt and pepper” like. These are the classic H&E features of neuroendocrine morphology. The tumor labels intensely with chromogranin and synaptophysin, confirming neuroendocrine differentiation by immunohistochemistry. These two features fulfill the requirements to diagnose a large cell neuroendocrine carcinoma, which is a high grade cancer.
Discussion: Metastatic squamous carcinoma is a significant consideration in this case. One could conceive of the lesion as showing basaloid features because of the peripheral palisading, and consider a basaloid squamous carcinoma. However, there is no true keratinization within the lesion, and the peripheral cells are larger than those of basaloid squamous carcinoma. The diffuse immunoreactivity for neuroendocrine markers essentially eliminates squamous carcinoma. A large cell carcinoma with neuroendocrine morphology shows the H&E features of neuroendocrine differentiation (nesting, peripheral palisading and rosette formation), but lacks immunohistochemical support for neuroendocrine differentiation in the form of specific chromogranin or synaptophysin immunoreactivity. Large cell carcinomas with neuroendocrine differentiation, on the other hand, do not show the classic H&E features of neuroendocrine morphology, but do demonstrate neuroendocrine differentiation by immunohistochemistry. The significance of the latter two diagnoses, particularly with respect to the tumor’s responsiveness to chemotherapy, remains an open question at this time.
Large cell neuroendocrine carcinoma features a nested growth pattern, polygonal cell shape, prominent nucleoli and a low N/C ratio. This contrasts with small cell (high grade neuroendocrine) carcinoma, which features a sheet-like growth pattern, fusiform nuclei, absence of nucleoli and a high N/C ratio with nuclear molding. These two entities make up the category of high grade neuroendocrine carcinoma in the lung. Both feature greater than 10 mitoses/10 hpf and abundant necrosis. Intermediate grade neuroendocrine carcinomas, or atypical carcinoid tumors, feature 2-10 mitoses/10 hpf, and spotty, comedo-type necrosis. Their architecture is typically nested. Low grade neuroendocrine carcinomas, or typical carcinoid tumors, do not have necrosis and have fewer than 2 mitoses/10 hpf.
Incorrect
Answer: Large cell neuroendocrine carcinoma
Histology: The tumor features large geographic areas of necrosis, and is composed of polygonal tumor cells with a high mitotic rate (greater than 1/high power field). The architecture of the tumor is nested, with peripheral palisading and occasional rosette formation. The chromatin is fine and “salt and pepper” like. These are the classic H&E features of neuroendocrine morphology. The tumor labels intensely with chromogranin and synaptophysin, confirming neuroendocrine differentiation by immunohistochemistry. These two features fulfill the requirements to diagnose a large cell neuroendocrine carcinoma, which is a high grade cancer.
Discussion: Metastatic squamous carcinoma is a significant consideration in this case. One could conceive of the lesion as showing basaloid features because of the peripheral palisading, and consider a basaloid squamous carcinoma. However, there is no true keratinization within the lesion, and the peripheral cells are larger than those of basaloid squamous carcinoma. The diffuse immunoreactivity for neuroendocrine markers essentially eliminates squamous carcinoma. A large cell carcinoma with neuroendocrine morphology shows the H&E features of neuroendocrine differentiation (nesting, peripheral palisading and rosette formation), but lacks immunohistochemical support for neuroendocrine differentiation in the form of specific chromogranin or synaptophysin immunoreactivity. Large cell carcinomas with neuroendocrine differentiation, on the other hand, do not show the classic H&E features of neuroendocrine morphology, but do demonstrate neuroendocrine differentiation by immunohistochemistry. The significance of the latter two diagnoses, particularly with respect to the tumor’s responsiveness to chemotherapy, remains an open question at this time.
Large cell neuroendocrine carcinoma features a nested growth pattern, polygonal cell shape, prominent nucleoli and a low N/C ratio. This contrasts with small cell (high grade neuroendocrine) carcinoma, which features a sheet-like growth pattern, fusiform nuclei, absence of nucleoli and a high N/C ratio with nuclear molding. These two entities make up the category of high grade neuroendocrine carcinoma in the lung. Both feature greater than 10 mitoses/10 hpf and abundant necrosis. Intermediate grade neuroendocrine carcinomas, or atypical carcinoid tumors, feature 2-10 mitoses/10 hpf, and spotty, comedo-type necrosis. Their architecture is typically nested. Low grade neuroendocrine carcinomas, or typical carcinoid tumors, do not have necrosis and have fewer than 2 mitoses/10 hpf.
