Small Cell Carcinoma and Other Neuroendocrine Tumors



Small Cell Carcinoma and Other Neuroendocrine Tumors


Gladell P. Paner, MD

Rafael E. Jimenez, MD





Key Facts


Terminology



  • NE tumors of prostate include spectrum of primary prostatic tumors exhibiting NE differentiation; in their pure form, they are analogous to NE tumors of other organ sites


  • Occur either as pure or admixed with acinar adenocarcinoma


  • Includes SCC, focal NE differentiation in acinar adenocarcinoma, carcinoid tumor, and LCNEC


Clinical Issues



  • SCC accounts for 1-5% of all prostate cancers, including SCC admixed with adenocarcinoma


  • Focal NE differentiation in acinar adenocarcinoma is reported in 10-100% of adenocarcinomas


  • Carcinoid tumor and LCNEC are exceedingly rare


  • Serum PSA level variable and may be normal


  • Prognosis of SCC is poor with mean survival of < 1 year after development of SCC component


Microscopic Pathology



  • SCC is histologically similar to SCC of lungs



    • Small blue cell tumor with scant cytoplasm, high nuclear to cytoplasmic ratio, “salt and pepper” chromatin, nuclear molding, single cell necrosis or geographic necrosis, and smearing artifacts


  • Focal NE differentiation in acinar adenocarcinoma



    • Characterized by scattered or focal cluster of NE cells blending with adenocarcinoma cellular elements, highlighted by NE markers


    • Paneth cell-like change may occur


  • Carcinoid tumor and LCNEC are histologically similar to their pulmonary counterparts


  • Up to 90% of NE tumors are NE marker (+)







Low-power magnification of SCC involving the prostate shows tumor cells arranged in haphazard nests and trabeculae with infiltration between benign glands.






SCC shows tumor cells with scant cytoplasm and nuclei with “salt and pepper” chromatin, indistinct nucleoli, and increased mitosis. Note nuclear molding and abundant apoptosis.


TERMINOLOGY


Abbreviations



  • Small cell carcinoma (SCC)


Synonyms



  • Small cell neuroendocrine (NE) carcinoma, poorly differentiated NE carcinoma, small cell anaplastic carcinoma, oat cell carcinoma


Definitions



  • NE tumors of prostate



    • Spectrum of primary prostatic tumors exhibiting NE differentiation which, in pure form, are analogous to NE tumors of other organ sites


    • NE tumors occur either as pure or admixed with acinar adenocarcinoma


    • WHO 2002 classification recognizes 3 forms of prostatic NE tumors



      • SCC, focal NE differentiation in acinar adenocarcinoma, and carcinoid tumor


  • SCC



    • High-grade NE carcinoma consisting of small to intermediate-sized NE tumor cells


  • Focal NE differentiation in acinar adenocarcinoma



    • Rare to occasional single or clusters of NE cells present in acinar adenocarcinoma, more often demonstrated by immunohistochemistry


  • Carcinoid tumor



    • Well-differentiated NE carcinoma


  • Large cell NE carcinoma (LCNEC)



    • High-grade NE carcinoma consisting of large-sized NE tumor cells, often with prominent nucleoli


    • Recently reported entity


  • Mixed acinar and SCC



    • Distinct components, ± juxtaposition, of usual acinar carcinoma and SCC


ETIOLOGY/PATHOGENESIS


Origin



  • Transdifferentiation or dedifferentiation from non-NE tumor cells


  • De novo transformation from prostatic NE cells



    • These are terminally differentiated postmitotic cells that evolved from committed basal cells and share common stem cell origin with acinar and basal cells


    • These NE cells are believed to play role in growth, differentiation, and homeostatic regulation of secretory processes of prostatic glands


Risk Factors



  • History of acinar adenocarcinoma, present in about 1/2 of SCC and most carcinoid tumors and LCNEC


  • Hormonal treatment or androgen deprivation therapy (ADT) for acinar adenocarcinoma



    • NE cells are devoid of androgen receptors; ADT may lead to clonal propagation


    • Possible clonal progression and evolution of subset of non-NE tumor cells that have been influenced by ADT


CLINICAL ISSUES


Epidemiology



  • Incidence



    • SCC accounts for approximately 1% of all prostate cancers, when SCC admixed with adenocarcinoma are included


    • Focal NE differentiation in acinar adenocarcinoma is almost ubiquitous, reported in 10-100% of adenocarcinomas, depending on technique employed


    • Carcinoid tumor and LCNEC are exceedingly rare, described only in isolated case reports and small case series



    • Poorly differentiated NE carcinomas arise in approximately 10% of prostate cancer patients with androgen-resistant disease following long-term ADT


  • Age



    • Tumors occur predominantly in elderly patients


    • SCC



      • Mean: 69 years; range: 30-92 years


Presentation



  • SCC



    • Rapid onset urinary tract obstruction, such as dysuria, nocturia, or urgency, are main presenting symptoms


    • Previous diagnosis of adenocarcinoma in 42-67% cases, some with history of prior hormonal therapy



      • Interval from adenocarcinoma to diagnosis of SCC ranges from 1 to 300 months; mean: 59 months


    • Lack of clinically evident hormone production in most cases


    • Paraneoplastic syndromes: Adrenocorticotrophic hormone (ACTH) or antidiuretic hormone (ADH) production, Eaton-Lambert syndrome, and others


    • Most patients present with extraprostatic extension, large primary tumor masses, advanced stage disease, and distant metastases


  • Carcinoid tumor



    • Incidental or may present with hematuria, burning, nocturia, frequency, oliguria, or symptoms of urinary retention


    • May occur following diagnosis of acinar adenocarcinoma


  • LCNEC



    • Most patients with initial diagnosis of acinar adenocarcinoma and prior ADT



      • Interval from adenocarcinoma to diagnosis of LCNEC ranges from 2 to 12 years; mean: 4.7 years


    • Advanced stage at time of diagnosis


    • Clinical and therapeutic significance of distinguishing LCNEC from SCC in prostate is not established


Laboratory Tests



  • Serum PSA level variable, may be normal


  • May show significant drop in serum PSA, as NE component predominates over acinar adenocarcinoma component


  • Serum chromogranin-A and pro-gastrin-releasing peptide levels



    • May be diagnostically and prognostically useful in prostate cancers with focal NE differentiation


    • May be useful particularly in androgen-independent cancers


Treatment



  • Surgery remains mainstream for therapy of SCC


  • Cisplatin-based chemotherapy has been suggested in SCC, but studies showing significant survival impact are lacking


Prognosis



  • Prognosis of SCC is poor with mean survival of < 1 year after development of SCC component



    • No difference in prognosis between pure SCC and SCC admixed with adenocarcinoma


    • Response to available treatment modalities is poor


    • Common metastatic sites include bone, liver, lung, and lymph nodes


  • Prognostic significance of focal NE differentiation in acinar adenocarcinoma is controversial



    • Some studies show negative effect on prognosis, while some studies show no relationship


    • Paneth cell-like change in adenocarcinoma does not portend poor prognosis


  • Prognosis of carcinoid tumor is uncertain because of few cases reported



    • Some tumors with clinically aggressive behavior may represent prostate adenocarcinoma (carcinoid-like adenocarcinoma)


    • True carcinoid is suggested to have indolent behavior, although cases reported are limited


  • Prognosis of LCNEC is similar to SCC



    • Most common metastatic site is bone; other sites of metastasis include lung, liver, lymph nodes



MACROSCOPIC FEATURES


General Features



  • Large volume disease frequently, with diffuse involvement of prostatic parenchyma


MICROSCOPIC PATHOLOGY


Histologic Features

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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Small Cell Carcinoma and Other Neuroendocrine Tumors

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