|Ahead of print publication
Neuroendocrine carcinoma of prostate presenting with ascites
Nishant Sagar1, Pritika Kushwaha1, Varuna Mallya1, Shyama Jain1, Nita Khurana1, NS Hadke2
1 Department of Pathology, Maulana Azad Medical College, New Delhi, India
2 Department of Surgery, Maulana Azad Medical College, New Delhi, India
Department of Pathology, Maulana Azad Medical College, New Delhi - 110 002
Source of Support: None, Conflict of Interest: None
Prostate cancer is a very common cause of morbidity and mortality in India. The commonest type of prostate carcinoma is adenocarcinoma, most of them are confined to prostate at the time of presentation. Bone is the preferred site for metastasis. The following is a case of neuroendocrine carcinoma of prostate arising in a 36 years old male who presented with ascitis and jaundice to the emergency department. The ascitic tap was positive for malignant cells. CECT done to detect primary showed osteoblastic secondaries in the spine along with lesions in the liver. DRE revealed grade 2 prostatomegaly. A TRUS guided biopsy showed neuroendocrine carcinoma of the prostate. Neuroendocrine carcinoma is a very rare type of prostatic carcinoma, with presentation of the same as ascitis is very uncommon. The following case is presented due to its rarity.
Keywords: Ascites, neuroendocrine carcinoma, prostate
| > Introduction|| |
Pure small cell prostate carcinoma (SCPC) is a tumor originating from neuroendocrine cells (NE) in the prostate. Major part of the prostatic epithelium is made up of glandular layer and basal layer, the NE cells which make up <1% of the total epithelium. Pure SCPC is a rare entity which constitute 1% of all prostatic malignancies with an incidence of 0.8% to 1.1%. In literature, 241 cases of SCCP have been reported so far out of which mere 20 cases have been reported in young patients with the age group <40 years., In Indian literature, only two such cases have been reported. This is possibly third such case of SCPC seen in a young male.,
| > Case Report|| |
A 36-year-old patient presented to surgery emergency with complaints of abdominal distention and yellow discoloration of skin with lower urinary tract symptoms since 2 months. Physical examination revealed ascites. Ascitic tap was done which showed cellular smear comprised of reactive mesothelial cells with interspersed small atypical cells with high N:C ratio and inconspicuous nucleoli [Figure 1]a. Contrast enhanced computed tomography (CECT) showed heterogeneously enlarged prostate with multiple metastatic deposits in spine and both lobes of the liver with enlarged abdominal nodes [Figure 1]b. Digital rectal examination (DRE) revealed Grade II prostatomegaly; the prostate was nodular and hard. In view of the heterogeneously enlarged prostate on CECT and a hard prostate on DRE, a serum prostate-specific antigen (PSA) was done and was found to be within normal limits (0.1 ng/ml). Transrectal ultrasound prostate biopsy-guided biopsy of prostate was advised and sample received for histopathological examination. Microscopy showed tumor composed of small round cells arranged in nests and sheets without any acinar pattern [Figure 2]a. On immunohistochemistry (IHC), these cells were positive for cytokeratin, chromogranin, and synaptophysin [Figure 2]b while negative for leukocyte common antigen (LCA). Based on the histopathology and IHC, a diagnosis of small cell carcinoma prostrate was rendered.
|Figure 1: (a) Ascitic fluid tap showing small atypical cells interspersed with mesothelial cells (Giemsa, ×100). (b) Contrast-enhanced computed tomography showing metastatic deposits in the spine|
Click here to view
|Figure 2: (a) Photomicrograph showing tumour cells arranged in sheets without any acinar arrangement (H and E, ×400). (b) Photomicrograph showing atypical cells positive for synaptophysin (IHC, ×100)|
Click here to view
| > Discussion|| |
According to latest WHO 2016 classification of prostatic malignancies, carcinoma with NE differentiation (NED) has been categorized as (I) conventional adenocarcinoma with NED, (II) well-differentiated NE tumor (carcinoid tumor), (III) small cell NE carcinoma, and (IV) large cell NE carcinoma.
SCPC is a high-grade neoplasm seen predominantly in the elderly population. Only a few cases have been reported in literature of its occurrence in young adults. SCPC is considered aggressive with frequent local spread and metastasis to lymph nodes, lung, liver, bones, urinary bladder, rectum, pericardium, and brain. The paraneoplastic syndrome has been reported in few cases due to the production of adrenocorticotropic hormone. Our case was a 36-year-old male presenting with widespread metastatic disease; however, our patient was a 36-year-old male. However, no symptoms suggestive of paraneoplastic syndrome were seen. The prognosis remains poor with median survival <5 months.
Serum PSA is an unreliable marker for SCPC as in majority of the cases, even with widespread metastasis, levels are within normal range as in our cases. The cases which have raised PSA have a mixed adenocarcinoma component.
The histological characteristics of SCPC include small round cells of size <3 small lymphocytes, nuclear molding, scant cytoplasm, and inconspicuous nucleoli. These cells are positive for NE markers such as chromogranin, synaptophysin, neuron-specific enolase, and CD56. A small subset of SCPC may be negative for all NE markers. PSA and androgen receptors are generally negative while Ki-67 is high highlighting its aggressive nature.,
The origin of SCPC remains controversial with some studies suggesting an origin from precursor uptake decarboxylation cells of local endodermal origin, while other studies suggest dedifferentiation from cells in adenocarcinoma. However, recent studies show that they rather arise from stem cells proven by lack of PSA expression and androgen receptor with high Ki-67 unlike seen in dedifferentiated carcinoma.
The differential diagnosis taken into account were includes lymphoma, embryonal rhabdomyosarcoma and desmoplastic small round cell tumor (DSRCT). Lymphoma and DSRCT were ruled out as the tumor cells were negative for LCA and desmin, respectively. Rhabdomyosarcomas are the common in prostrate and urinary bladder and are seen in childhood. Only a few cases have been reported in adults. Lack of pleomorphism and negativity for desmin ruled out the possibility of rhabdomyosarcomas.
The management of SCPC remains blurred as there are no well-established guidelines due to paucity of cases. Hormone therapy and orchidectomy are generally not recommended as these cases are androgen receptor negative. SCPC is more sensitive to chemotherapeutic agents such as etoposide and cisplatin. Surgery may be beneficial for patient with limited local disease. Our patient could not complete his chemotherapy regime and succumbed to the disease 1 month after diagnosis.
| > Conclusion|| |
SCPC is an aggressive neoplasm seen predominantly in elderly patients with rare case reports in young patients. Clinicoradiological features may be deceptive. The early prostatic biopsy is warranted as conclusive opinion may be possible only after histomorphological and immunohistochemical correlation.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Parimi V, Goyal R, Poropatich K, Yang XJ. Neuroendocrine differentiation of prostate cancer: A review. Am J Clin Exp Urol 2014;2:273-85.
Gupta P, Dadhwal US. A rare variant of prostate cancer in a young adult male of Asian origin. J Med Sci Clin Res 2015;3:4257-60.
Deorah S, Rao MB, Raman R, Gaitonde K, Donovan JF. Survival of patients with small cell carcinoma of the prostate during 1973-2003: A population-based study. BJU Int 2012;109:824-30.
Kumar V, Khurana N, Rathi AK, Malhotra A, Sharma K, Abhishek A, et al.
Primitive neuroectodermal tumor of prostate. Indian J Pathol Microbiol 2008;51:386-8.
] [Full text]
Trotz C. Prostate cancer with a normal PSA: Small cell carcinoma of the prostate – A rare entity. J Am Board Fam Pract 2003;16:343-4.
Hasigov A, Ndamba Engbang JP, Tlatov T, Aleksandre E. Small cell carcinoma of prostate: A case report of a patient with a normal PSA and a giant prostate volume. GMJ 2016;1:12-6.
Li Q, Zhang CS, Zhang Y. Molecular aspects of prostate cancer with neuroendocrine differentiation. Chin J Cancer Res 2016;28:122-9.
Cecen K, Karadag MA, Demir A, Kocaaslan R. Small cell carcinoma of the prostate presenting with skin metastasis: A case report. J Med Case Rep 2014;8:146.
Huang IS, Huang JS, Alex TL. Lin TL, Chen KK. Small cell carcinoma of the prostate: Three case reports and a literature review. Urol Sci 2013;24:131-5.
Guo A, Wen S, Ma Y, Wei L, Liu A. Clinicopathological analysis on small cell carcinoma of the prostate in Chinese patients. J Cancer 2014;5:797-803.
[Figure 1], [Figure 2]