Small cell carcinoma of the prostate

Last revised by Joachim Feger on 11 Feb 2022

Small cell carcinomas of the prostate (SCCP) or small cell neuroendocrine carcinomas of the prostate are neuroendocrine tumors and are characterized by aggressive behavior and a proliferation of small cells.

Small cell neuroendocrine carcinomas of the prostate are rare 1,2 and make up for <1% of prostate cancers 3.

Small cell neuroendocrine carcinomas might be associated with the following 1,2:

Small cell neuroendocrine carcinomas of the prostate are mainly diagnosed based on histopathological and immunohistochemical features.

Due to relative low prostate-specific antigen (PSA) level in relation to tumor extent, tumor detection is more difficult and patients frequently present with voiding difficulties, hematuria, constitutional or neurological symptoms due to paraneoplastic syndromes or metastases. They might be also incidentally found on imaging studies 1-4.

Tumor markers such as CEA, Ca19-9, plasma CgA, neuron-specific enolase, 5-hydroxytryptamine, bombesin or gastrin might be positive 1.

Small cell carcinomas are high-grade epithelial neoplasms of the prostate 4. They resemble small cell carcinoma of the lung 1 and might be associated with adenocarcinoma of the prostate

They often cause osteolytic bone metastases and metastases to other organs like the lung brain or liver 3,4.

Macroscopically small cell carcinomas of the prostate are usually larger on detection and have ill-defined borders 1

Microscopically small cell carcinomas of the prostate are characterized by strict morphological features which include 1-3:

  • proliferation of small cells with >4 lymphocytes per diameter
  • scant cytoplasm
  • fine granular ‘salt and pepper’ chromatin
  • necrosis and apoptosis with a large number of apoptotic bodies
  • absence of prominent nucleoli, frequent nuclear molding
  • positive crush artifact
  • high mitotic count
  • high nuclear to cytoplasmic ratio
  • variably tumor giant cells

The small cell component of immunohistochemistry stains usually expresses neuroendocrine markers as synaptophysin, neuron-specific enolase, chromogranin or CD56 1. About half of the tumors show positivity in thyroid transcription factor (TTF-1) 2,3. Typical prostatic markers as the prostate-specific antigen (PSA) or P501S are only positive in about 1/6 to 1/4 of the cases 1.

Fusions of the TMPRSS2 and ERG genes might be found with small cell carcinomas of the prostate 1-3. Other mutations include the N-MYC and the RB1 gene 4.

Small cell carcinomas of the prostate might show the following radiographic features:

  • local organ invasion e.g. bladder or rectum
  • enlarged pelvic lymph nodes
  • metastases to other organs than bone e.g. brain, lung or liver metastases
  • osteolytic bone metastases 

The appearance of small cell carcinoma of the prostate has been described as irregular heterogeneous isoechoic to hypoechoic.

Due to their rare occurrence, there is still a paucity of radiological descriptions of small cell carcinomas of the prostate. They tend to be large and heterogeneous 5.

  • T1: heterogeneous low to intermediate signal intensity
  • T2: heterogeneously high signal intensity
  • DWI: heterogeneous hyperintense on high b-value with moderate low signal intensity on ADC
  • DCE (Gd): avid enhancement 

The radiological report should include a description of the following features:

The prognosis of small cell carcinoma of the prostate is poor 1 and median survival rates are estimated to be 1-2 years after the time of diagnosis 3. Response to androgen deprivation therapy (ADT) is usually poor 1.

Management of small cell carcinoma of the prostate is not well delineated but because of its aggressiveness, a multimodality approach is usually adopted 2,3. Prostatectomy alone has been curative only on rare occasions which might be partly due to the fact that it commonly presents with higher tumor stages and metastases. Similarly to other small cell carcinomas, they tend to be sensitive to chemotherapy and radiotherapy for a transient period 1. Similar to small cell cancer of the lung platinum-containing agents as cisplatin or etoposide has been used in addition to docetaxel 1,3,4.

Conditions and tumors that can mimic the clinical presentation or imaging appearance of small cell carcinoma of the prostate include:

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Cases and figures

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