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| CASE REPORT |
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| Year : 2019 | Volume
: 2
| Issue : 1 | Page : 27-29 |
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Neuroendocrine variant of carcinoma of the prostate
RB Nerli1, Shridhar C Ghagane2, K Shankar3, Rafat Jamadar K2, Sushant Deole3, Neeraj S Dixit2, Murigendra B Hiremath4
1 Department of Urology, JN Medical College, KLE Academy of Higher Education and Research (Deemed-to-be-University), JNMC Campus; KLES Kidney Foundation, KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi, Karnataka, India
2 Department of Urology, KLES Kidney Foundation, KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi, Karnataka, India
3 Department of Urology, JN Medical College, KLE Academy of Higher Education and Research (Deemed-to-be-University), JNMC Campus, Belagavi, Karnataka, India
4 Department of Biotechnology and Microbiology, Karnatak University, Dharwad, Karnataka, India
| Date of Submission | 03-Dec-2018 |
| Date of Acceptance | 13-Feb-2019 |
| Date of Web Publication | 3-Jun-2019 |
Correspondence Address:
Dr. R B Nerli
Department of Urology, JN Medical College, KLE Academy of Higher Education and Research (Deemed-to-be-University), JNMC Campus, Belagavi - 590 010, Karnataka
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/IJNO.IJNO_14_18
Alterations in the differentiation pathway of prostate cancer can be seen in a small proportion of patients, giving rise to a neuroendocrine (NE) variant. Such tumors possess a number of biologic characteristics unique to NE tumors that can also arise from other organs. Rapidly growing disease with the following clinical characteristics such as pelvic masses, visceral involvement, osteolytic metastasis with hypercalcemia, and brain metastasis should prompt evaluation for the NE variant. We report a case of NE variant of prostatic carcinoma presenting in an elderly male and rapidly progressing to metastasize even the brain.
Keywords: Carcinoid, large-cell neuroendocrine carcinoma, neuroendocrine differentiation, Paneth cell like, prostate adenocarcinoma, small-cell carcinoma
How to cite this article:
Nerli R B, Ghagane SC, Shankar K, RafatJ, Deole S, Dixit NS, Hiremath MB. Neuroendocrine variant of carcinoma of the prostate. Int J Neurooncol 2019;2:27-9 |
| Introduction | |  |
The World Health Organization (WHO) classification of epithelial and neuroendocrine (NE) tumors of the prostate was summarized in 2016 by Moch et al.[1] More than 95% of all carcinomas of the prostate (CaP) are referred to as acinar, conventional, or usual type.[1],[2] Acinar adenocarcinoma is an invasive CaP consisting of malignant prostatic epithelial cells arranged in a variety of architectural patterns, such as glands, sheets, cords, and single cells. Basal cells are either absent or not seen.
A small percentage (<5%) of cancers of the prostate are classified as variants.[1] Variant is the word usually used to describe distinctively different morphotypes of a certain neoplasm. Morphological variants of acinar adenocarcinoma are important as they cause difficulties in making a diagnosis and have varied prognosis when compared with acinar adenocarcinoma.[1],[2],[3] As per the WHO definition, prostate cancers with NE differentiation include usual adenocarcinoma with NE differentiation, adenocarcinoma with Paneth cell-like NE differentiation, carcinoid tumor, small-cell NE carcinoma, and large-cell NE carcinoma.[1],[4],[5] We report a case of NE variant of prostatic carcinoma presenting in an elderly male and rapidly progressing to metastasize even the brain.
| Case Report | | |
A 77-year-old male presented with lower urinary tract symptoms of 1-month duration. The patient also complained of severe pain in the lower back region, pelvis, thigh, and buttocks. The pain was severe and disturbed the physical activities of the patient. The patient was a diabetic and hypertensive on oral medications. On examination, the patient had a huge, hard, and nodular prostate. Serum prostate-specific antigen (PSA) was 10.2 ng/ml. Ultrasonography revealed a 108-cc prostate with mixed-echo pattern. Multiparametric magnetic resonance (MR) imaging of the pelvis showed an enlarged prostate (5.6 cm × 6.0 cm × 5.2 cm) with heterogeneous intensity [Figure 1]. Anteriorly, the fat planes between the prostate and urinary bladder were indistinct. On contrast study, the enlarged prostate showed heterogeneous enhancement. On MR spectroscopy, few areas of elevated choline/citrate and creatine/citrate ratios were noted (suspicious for malignancy). Bilateral enlarged heterogeneously enhancing lymph nodes were noted in external iliac, internal iliac, common iliac, and obturator group. These lymph node masses were of >2.5 cm in size. | Figure 1: (a) Magnetic resonance imaging of the pelvis shows an enlarged prostate (5.6 cm × 6.0 cm × 5.2 cm) with heterogeneous intensity. (b) Anteriorly, the fat planes between the prostate and urinary bladder appear to be indistinct
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In view of these clinical findings, a 12-core ultrasound-guided prostatic biopsy was done. The histopathological examination revealed CaP and Gleason grade 4 + 5 in 5 of the 12 cores. In view of severe pain, the patient was given injection degarelix 240 mg. The histopathological slides were reviewed with immunohistochemistry (IHC), and a diagnosis of NE carcinoma was made. IHC showed neoplastic cells expressing synaptophysin and chromogranin. They were negative for alpha-methylacyl-CoA racemase. Ki-67 index was 90%. A gallium-68 prostate-specific membrane antigen and gallium-68 DOTANOC positron emission tomography (PET) scan were done, which revealed prostatomegaly with enhancing lesion involving the entire prostate and right seminal vesicle [Figure 2] and [Figure 3]. Multiple mesorectal and presacral lymph nodes showed metastases. Enlarged bilateral pelvic and retroperitoneal lymph nodes were enlarged due to metastases. A small lesion of 5 mm was seen in the right occipital lobe. | Figure 2: (a) Positron emission tomography-computed tomography shows prostatomegaly with infiltration of the right seminal vesicle. (b and c) Multiple lymph nodes at the level of internal and external iliac, obturator, and common iliac lymph nodes were seen. (d) Small enhancing 5-mm lesion was seen in the right occipital lobe
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 | Figure 3: Gallium-68 prostate-specific membrane antigen and gallium-68 DOTANOC positron emission tomography scan shows prostatic mass with extension in the seminal vesicle and deposits infiltrating lateral rectal wall, mesorectal and presacral lymph nodes, and enlarged pelvic and retroperitoneal lymph nodes
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In view of metastatic disease and histopathological report, the patient was started on chemotherapy which included etoposide and carboplatin. The patient completed six cycles of chemotherapy and hormone therapy in the form of injection degarelix. Serum PSA came down to 0.42 ng/ml (6 months after diagnosis). Repeat PET scan showed persistent metabolically active disease in the prostate and left pelvic lymph nodes. MR imaging of the brain showed peripherally enhancing lesions involving the supra- and infratentorial region and midbrain due to metastases. The patient has been progressively deteriorating with loss of weight, appetite, and general well-being.
| Discussion | | |
A minority of cancers of the prostate (<5%) have been classified as variants as per the WHO classification. Variants usually pose a challenge in making a final diagnosis and include deceptively benign-looking forms.[1] Some of these have a prognosis worse than the usual acinar adenocarcinoma. Some of these variants are commonly seen after endocrine and radiation therapy. NE tumors, sarcomatoid carcinoma, and pleomorphic giant cell variants are a few of them.[4]
NE cells (NEC) are scattered within the prostatic glands in all anatomic zones and comprise <1% of benign prostatic glandular epithelium.[4] These cells show characteristic lateral spreading of dendritic processes; however, they cannot be usually recognized on routine hematoxylin and eosin staining. These cells are best recognized using IHC with specific NEC markers.[2],[4] These cells (NEC) are believed to play an important role in neuronal and endocrine regulation of benign prostate; however, their precise function is not entirely clear.
NE prostatic carcinomas are considered as a special type of NE differentiation of prostatic epithelial neoplasms.[3] NE CaP may represent a subset of prostate cancer phenotypes which may be linked to resistance to androgen receptor signaling inhibition with aggressive tumor characteristics and a largely dismal prognosis.[3] NE prostatic carcinomas may be diagnosed on primary prostate needle biopsy or on biopsies of metastatic lesions with negative or low PSA levels. Based on morphological characteristics, proliferative index, and grade, this tumor can be subdivided into small-cell carcinomas, large-cell NE carcinomas, and carcinoid tumors.
The treatment of NE carcinoma is often similar to that of patients with other NE tumors (e.g., small-cell carcinoma of the lung) and usually includes combinations of cisplatin and etoposide or the combination of docetaxel plus carboplatin.[2],[4] Radiation therapy is effective and should be considered in cases with bulky disease, with brain metastasis, or when local disease control in critical areas may have a positive impact on quality of life (pain, potential pathologic fractures, and bladder outlet obstruction).[2] A combined chemotherapy and radiation therapy approach is commonly used so as to accomplish maximal disease control. Despite high initial response rates with chemotherapy and radiation treatment, the prognosis of these patients remains poor and is dependent on various factors, including extent and location of metastases. In general, survival is <12 months.[2]
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
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Moch H, Humphrey PA, Ulbright TM, Reuter V. WHO Classification of Tumours of the Urinary System and Male Genital Organs. Lyon, France: International Agency for Research on Cancer; 2016.  |
| 2. | Antonarakis ES, Carducci MA, Eisenberger MA. Treatment of castration resistant prostate cancer. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, editors. Campbell-Walsh Urology. 11 th Rev. Philadelphia: Elsevier; 2016. p. 2804-22. |
| 3. | Ghagane SC, Nerli RB, Hiremath MB, Wagh AT, Magdum PV. Incidence of prostate cancer at a single tertiary care center in North Karnataka. Indian J Cancer 2016;53:429-31. [ PUBMED] [Full text] |
| 4. | Santoni M, Conti A, Burattini L, Berardi R, Scarpelli M, Cheng L, et al. Neuroendocrine differentiation in prostate cancer: Novel morphological insights and future therapeutic perspectives. Biochim Biophys Acta 2014;1846:630-7. |
| 5. | Priemer DS, Montironi R, Wang L, Williamson SR, Lopez-Beltran A, Cheng L, et al. Neuroendocrine tumors of the prostate: Emerging insights from molecular data and updates to the 2016 World Health Organization classification. Endocr Pathol 2016;27:123-35. |
[Figure 1], [Figure 2], [Figure 3]
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