Small cell carcinoma of the prostate

Small cell carcinomas of the prostate (SCCP) or small cell neuroendocrine carcinomas of the prostate are neuroendocrine tumours and are characterised by aggressive behaviour and a proliferation of small cells.

Epidemiology

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

Associations

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

• prostatic adenocarcinoma in up to 50%
• paraneoplastic syndromes
  • Cushing's syndrome
  • syndrome of inappropriate antidiuretic hormone secretion (SIADH)
  • limbic encephalitis

Clinical presentation

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

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

Pathology

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

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

Macroscopic appearance

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

Microscopic appearance

Microscopically small cell carcinomas of the prostate are characterised 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 moldingmoulding
• positive crush artifact
• high mitotic count
• high nuclear to cytoplasmic ratio
• variably tumour giant cells

Immunophenotype

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

Genetics

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.

Radiographic features

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 

Ultrasound

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

MRI

Due to its 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.

Signal characteristics

• 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 

Radiology report

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

• form, location and size
• tumour margins
• extraprostatic extension
• seminal vesicle invasion
• bladder or rectal invasion
• suspicious or enlarged lymph nodes 

Treatment and prognosis

The prognosis of small cell carcinoma of the prostate is poor ¹ and median survival rates are estimated 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 inon rare occasions which might be partly due to the fact that it commonly presents with higher tumour stages and metastases. Similar to other small cell carcinomas and 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 havehas been used in addition to docetaxel ^1,3,4.

Differential diagnosis

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

• benign prostatic hyperplasia
• prostate adenocarcinoma
• other neuroendocrine tumours of the prostate
  • adenocarcinoma with neuroendocrine differentiation
  • well-differentiated neuroendocrine tumour
  • large cell carcinoma