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Presented by Dr. Jonathan Epstein and prepared by Dr. Kevan Salimian
A 67 year old man was diagnosed with tumor on needle biopsy and underwent a radical prostatectomy. A ki67 was performed which showed 10% positivity.
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1. Question
A 67 year old man was diagnosed with tumor on needle biopsy and underwent a radical prostatectomy. A ki67 was performed which showed 10% positivity.
Choose the correct diagnosis:
Correct
Answer: D. Carcinoid
Histology: The tumor consists of large islands of tumor with surrounding dense hyalinized stroma. Within the islands are ribbons of cells with round uniform nuclei with delicate “salt and pepper” chromatin and a moderate amount of eosinophilic cytoplasm. Scattered mitotic figures are noted. In the center of the nests are sheets of pyknotic dyscohesive tumor cells which looks different from the surrounding more organoid appearance. The tumor lacked necrosis, except for a small area that probably was from the prior biopsy. Extensive lymph-vascular space invasion and extraprostatic extension was present. Submitted immunohistochemical stains demonstrated the following results: The neoplastic cells were positive for synaptophysin, chromogranin, CK20 focally and negative for NKX3.1, CK7, GATA, p501S and p63.
Discussion:
Small cell carcinoma is a high grade tumor defined by characteristic nuclear features, including lack of prominent nucleoli, nuclear molding, fragility, and crush artifact. High nuclear to cytoplasmic ratio and indistinct cell borders are characteristic, as is a high mitotic rate and apoptotic bodies. In contrast to a small cell carcinoma, the tumor in this case has a prominent endocrine appearance with ribbons and cords of tumor, more typical of well-differentiated NE tumor (carcinoid) as opposed to small cell carcinoma. Many of the more solid sheet-like appearing areas are poorly preserved and are an artifact of poor cellular preservation. The absence of increased mitotic activity and lack of high Ki-67 proliferative index are also not consistent with a high grade NE carcinoma. The extensive lymph-vascular space invasion and extraprostatic extension is still consistent with an intermediate grade NE tumor, albeit one with an increased risk of aggressive behavior.
True carcinoid tumors of the prostate are extremely rare. In order to diagnose a carcinoid of the prostate and distinguish it from a prostate adenocarcinoma with carcinoid-like features, the following features should be present: 1) Not closely associated with concomitant adenocarcinoma of the prostate; 2) Immunohistochemically positive for NE markers and negative for PSA and other prostatic markers, and 3) Originating in the prostatic parenchyma. Of the cases in the literature, there are only 5 cases satisfy this definition. Two cases were in men in their 30s, younger than typically seen with adenocarcinoma of the prostate. The remaining three cases were in even younger males with multiple endocrine neoplasia (MEN) IIB syndrome. Patients were 7, 19, and 22 years of age. Although the data is limited, prostatic carcinoids tend to present with locally advanced disease, including some with regional lymph node metastases yet still have a favorable prognosis. It is reasonable for these true carcinoids to grade them in an analogous fashion to those of gastrointestinal tract based on mitotic rates and Ki-67 proliferation rates. Most cases reported with carcinoid-like morphology have admixed usual prostate cancer or the carcinoid-like tumor expressed PSA. Clinically, carcinoid-like adenocarcinomas have behaved like ordinary prostate carcinomas and in none of these cases has a carcinoid syndrome been present. Prostate-specific acid phosphatase immunoreactivity is not discriminatory in the assessment of whether a tumor is a true carcinoid or adenocarcinoma with carcinoid-like features as even some non-prostatic carcinoid tumors express PSAP.
Large cell neuroendocrine carcinoma (LCNEC) of prostate is exceptionally rare, particularly its pure form. The largest series by Evans et al. describes seven cases of LCNEC, only one pure and apparently de novo. Six other cases represented progression from prior typical prostate adenocarcinoma, following longstanding hormonal therapy. According to the authors, the large cell neuroendocrine component was composed of sheets and ribbons of amphophilic cells with large nuclei, coarse chromatin and prominent nucleoli. Mitotic activity was high, and foci of necrosis were present. The LCNEC component was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S. Ki67 proliferative index was >50%.Incorrect
Answer: D. Carcinoid
Histology: The tumor consists of large islands of tumor with surrounding dense hyalinized stroma. Within the islands are ribbons of cells with round uniform nuclei with delicate “salt and pepper” chromatin and a moderate amount of eosinophilic cytoplasm. Scattered mitotic figures are noted. In the center of the nests are sheets of pyknotic dyscohesive tumor cells which looks different from the surrounding more organoid appearance. The tumor lacked necrosis, except for a small area that probably was from the prior biopsy. Extensive lymph-vascular space invasion and extraprostatic extension was present. Submitted immunohistochemical stains demonstrated the following results: The neoplastic cells were positive for synaptophysin, chromogranin, CK20 focally and negative for NKX3.1, CK7, GATA, p501S and p63.
Discussion:
Small cell carcinoma is a high grade tumor defined by characteristic nuclear features, including lack of prominent nucleoli, nuclear molding, fragility, and crush artifact. High nuclear to cytoplasmic ratio and indistinct cell borders are characteristic, as is a high mitotic rate and apoptotic bodies. In contrast to a small cell carcinoma, the tumor in this case has a prominent endocrine appearance with ribbons and cords of tumor, more typical of well-differentiated NE tumor (carcinoid) as opposed to small cell carcinoma. Many of the more solid sheet-like appearing areas are poorly preserved and are an artifact of poor cellular preservation. The absence of increased mitotic activity and lack of high Ki-67 proliferative index are also not consistent with a high grade NE carcinoma. The extensive lymph-vascular space invasion and extraprostatic extension is still consistent with an intermediate grade NE tumor, albeit one with an increased risk of aggressive behavior.
True carcinoid tumors of the prostate are extremely rare. In order to diagnose a carcinoid of the prostate and distinguish it from a prostate adenocarcinoma with carcinoid-like features, the following features should be present: 1) Not closely associated with concomitant adenocarcinoma of the prostate; 2) Immunohistochemically positive for NE markers and negative for PSA and other prostatic markers, and 3) Originating in the prostatic parenchyma. Of the cases in the literature, there are only 5 cases satisfy this definition. Two cases were in men in their 30s, younger than typically seen with adenocarcinoma of the prostate. The remaining three cases were in even younger males with multiple endocrine neoplasia (MEN) IIB syndrome. Patients were 7, 19, and 22 years of age. Although the data is limited, prostatic carcinoids tend to present with locally advanced disease, including some with regional lymph node metastases yet still have a favorable prognosis. It is reasonable for these true carcinoids to grade them in an analogous fashion to those of gastrointestinal tract based on mitotic rates and Ki-67 proliferation rates. Most cases reported with carcinoid-like morphology have admixed usual prostate cancer or the carcinoid-like tumor expressed PSA. Clinically, carcinoid-like adenocarcinomas have behaved like ordinary prostate carcinomas and in none of these cases has a carcinoid syndrome been present. Prostate-specific acid phosphatase immunoreactivity is not discriminatory in the assessment of whether a tumor is a true carcinoid or adenocarcinoma with carcinoid-like features as even some non-prostatic carcinoid tumors express PSAP.
Large cell neuroendocrine carcinoma (LCNEC) of prostate is exceptionally rare, particularly its pure form. The largest series by Evans et al. describes seven cases of LCNEC, only one pure and apparently de novo. Six other cases represented progression from prior typical prostate adenocarcinoma, following longstanding hormonal therapy. According to the authors, the large cell neuroendocrine component was composed of sheets and ribbons of amphophilic cells with large nuclei, coarse chromatin and prominent nucleoli. Mitotic activity was high, and foci of necrosis were present. The LCNEC component was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S. Ki67 proliferative index was >50%.
