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Metastasis of Primary Signet ring cell carcinoma of prostate to bone marrow: A rare occurrence with review of literature

 Department of Hematology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

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Date of Submission30-Aug-2020
Date of Decision24-Mar-2021
Date of Acceptance11-Apr-2022
Date of Web Publication07-Feb-2023


We report a case of a 65-year-old male who presented with multiple enlarged intraabdominal lymph nodes with lytic lesions over pelvic and lumbar vertebrae. His serum prostate-specific antigen (PSA) was markedly raised. Bone marrow investigation revealed the presence of diffuse infiltration of single cells having hyperchromatic nuclei, moderate amount of eosinophilic cytoplasm, and eccentrically placed nuclei resembling signet ring cells. Hence, a diagnosis of metastatic signet cell carcinoma of prostate was made on bone marrow biopsy. This variant of prostatic carcinoma is very rare and accounts for only 2.5% of all prostatic adenoacarcinomas that make our case worth reporting. To emphasize the rare occurrence of this variant, we performed a Pubmed-based literature review of 25 years.

Keywords: Adenocarcinomas, bone marrow, metastasis, prostate, PSA, signet cell

How to cite this URL:
Jamal I, Raman RB, Kumar S, Agrawal R, Choudhary VN. Metastasis of Primary Signet ring cell carcinoma of prostate to bone marrow: A rare occurrence with review of literature. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Mar 28]. Available from:

   Introduction Top

Primary signet cell carcinoma of prostate (SRCC) is quite a rare tumor and very few case reports have been described in the literature showing metastasis to bone marrow.[1] Prostate SRCC is diagnosed by eliminating of other organs such as colon and stomach, pancreas, breast, thyroid, and bladder. Prognosis is worse than classical prostatic adenocarcinoma and therapeutic management is also different. Only 69 cases have been reported in the English literature since 1979.[2]

We performed a Pubmed-based literature review from 1981 to 2020 with key words like primary, prostatic, signet ring cell, and carcinoma. Thirty articles were studied by the authors and their findings were highlighted. A total of 18 cases including our present case has been described in the literature that makes this rarity a rare occurrence.

   Case Report Top

A 65-year-old male presented with bilateral lower limbs swelling, body ache and weakness, and dysuria for 3 months. Clinical and radiological examination of rectum was normal. USG abdomen revealed multiple enlarged retroperitoneal, para-aortic, and bilateral inguinal lymph nodes, largest measuring 35 x 20 mm in size. Retroperitoneal lymph nodes were seen entrapping the left ureter causing left-sided hydronephrosis. USG also showed metastatic lesion in segment IV of liver and lytic lesions in pelvis and lumbar vertebra and few enlarged retroperitoneal lymph nodes. USG, CT abdomen, and endoscopy of gastrointestinal tract failed to show any abnormality. Tumor markers like CEA were 12 IU/litre and serum PSA was markedly raised with an exact value being 151 ng/ml. Per rectal digital examination of prostate revealed an enlarged and mildly tender prostate. USG prostate showed a hypoechoic lesion in the peripheral zone of the gland measuring 1.5 x 1.3 cm. CA19.9 was normal. Due to the morbid condition of the patient, prostatic biopsy was not performed. CBC showed Hb of 4.4 gm/dl, total WBC count of 6.6 X 109 cells/liter, and platelets of 200 X109/liter. USG-guided FNAC retroperitoneal lymph node was done that showed few clusters of malignant epithelial cells having high N/C ratio, hyperchromatic nuclei, and scant amount of cytoplasm. A diagnosis of metastatic poorly differentiated carcinoma was made on fine needle aspiration cytology (FNAC) [Figure 1]a. Bone marrow aspiration was difficult to perform and attempted twice as the bone was too thick and yielded a non-diagnostic aspirate each time. Bone marrow biopsy was performed that revealed the presence of diffuse infiltration of single cells having hyperchromatic nuclei and moderate amount of eosinophilic cytoplasm. Extensive fibrosis was noted in intertrabecular spaces with marked suppression of trilineage hematopoeisis. Bony trabeculae were also a bit sclerotic [Figure 1]b, [Figure 1]c, [Figure 1]d. Immunohistochemistry (IHC) with EMA and anti-PSAP showed diffuse membranous and cytoplasmic positivity [Figure 2]a and [Figure 2]b. After an extensive clinico radiological and serological work up that included ultrasonography (USG) and computed tomography (CT) scan, abdomen and pelvis, endoscopy, and tumor markers estimation like CEA, CA19.9, CA 125, etc., a diagnosis of metastatic signet cell carcinoma of prostate was made on histopathology and further confirmed by IHC.
Figure 1: (a) FNAC microphotograph of retroperitoneal lymph node showed presence of malignant epithelial cells in clusters having high N/C ratio, scanty cytoplasm, and hyperchromatic nuclei. (Giemsa stain; 400X) (b) Microphotograph of bone marrow biopsy showing presence of diffuse infiltration of single cells with fibrosis and sclerotic bony trabeculae (H & E; 100X) (c) Microphotograph of bone marrow biopsy showing infiltration by signet cells having abundant eosinophilic cytoplasm and eccentrically located hyperchromatic nuclei (H & E; 400X) (d) Microphotograph of bone marrow biopsy showing signet cells in higher magnification (H&E; 1000X)

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Figure 2: (a) IHC microphotograph showing anti-PSAP positivity (DAB; 400X) (b) IHC microphoptograph showing EMA positivity (EMA.400X)

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   Discussion Top

Although SRCC is primarily found in the stomach and colon, it can also be found in the pancreas, breast, thyroid, bladder, and prostate.[3] Signet ring is a term used to describe the histologic appearance of a tumor cell characterized by compression of the nucleus into the form of a crescent by a large cytoplasmic vacuole.[4] Signet ring cell changes were first described in 1981 and are estimated to occur in 2.5% of cases of adenocarcinoma of the prostate.[5] Regardless of histologic classification, the grim prognosis and rarity of SRCC of the prostate warrants detailed investigation. A detailed work up for primary signet cell carcinoma at other more common sites like gastrointestinal tract should be carried out including USG, CT, and endoscopy before labeling it primary SRCC of prostate.

Other variants of prostate adenocarcinoma are often confused with SRCC.[5],[6] Mucinous carcinoma with signet ring cells is diagnosed when at least 25% of the tumor is constituted of extracellular mucin and less than 25% of tumor cells feature signet rings.[7],[8],[9],[10]

Only 69 cases have been reported in the English literature since 1979.[2] We reviewed previous English reports and found 18 reported cases of primary SRCC of the prostate including our present case from 1981 to 2020 including both the years. [Table 1] shows the comparison of various prostatic SRCC. Because of its rarity, no recommended treatment has been established. It is of utmost importance that we should differentiate between tumors of GIT and prostate origin as the treatment modality of these two is quite different. In the literature review, the median age for prostatic SRCC is around 68 years, which is comparable to the currently reported 65 years.
Table 1: Showing Pubmed based literature search of previous cases of signet ring cell carcinoma of prostate

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The signet ring appearance in the cells occurs because the nucleus is pushed to the periphery of the cell by large intracytoplasmic vacuoles. SRCC is most commonly observed in the GI tract. Therefore, when SRCC is detected in the prostate, endoscopy, colonoscopy, and abdominal CT scan are needed to exclude metastasis. This case presented here did not show any GI tract pathology. Based on these findings, we made the diagnosis of primary prostatic SRCC. Some studies stated that signet ring cells must constitute at least 20–25% of the tumor to have a diagnosis of primary prostatic SRCC, although other studies stated that a certain ratio of cells was not needed for diagnosis.[11],[12],[13] In this case, the signet ring cell component constituted almost 50% of the tumor. Primary prostatic SRCC is frequently accompanied by high-grade prostate adenocarcinoma patterns; therefore, it might be a variant of a high-grade adenocarcinoma rather than a separate pathological diagnosis. Histologic criteria for SRCC of the prostate are highly variable.[14],[16] In the literature, the median age for prostatic SRCC is around 68 years, which is comparable to the currently reported 65 years. Previous studies showed that the survival rates after the initial diagnosis were 82.3% in the first year, 54.7% in the third year, and 11.7% in the fifth year.[17],[18] Warner et al.[19] showed an average survival time of 29 months.

Histologic criteria for SRCC of the prostate are variable in the literature available. Some publications suggest that malignant cells should be negative for leukocyte common antigen and alpha–smooth muscle actin and carcinoembryonic antigen.[22] It has been mentioned in the report that 87% of primary SRCC of prostate are PSA and PSAP positive. Other IHC stains to confirm primary prostate tumor are α-methylacyl coenzyme A racemase (P504S) and cytokeratin 5/6.[23],[24] The cytoplasmic vacuoles contain lipid or mucin and stain positive with mucicarmine in about 50% of cases, PAS in about 60%, and alcian blue in 60%. Some authors believed that signet cells should constitute 20-50% of the tumor; however, this criterion is not followed strictly as cases with 5% to 50% have been accepted as SRCC of the prostate. In our review of the literature, 84% of patients had reports of signet ring cells constituting more than 20% of the specimen.[25],[26] Guerin et al.[27] proposed that SRCC should be classified as a variant of high-grade adenocarcinoma rather than a separate histologic diagnosis. In support of this proposition, SRCC is often found in the presence of other high-grade prostatic adenocarcinoma patterns. Reyes et al.[28] described 3 cases in which high-grade prostatic intraepithelial neoplasia had adjacent SRCC.

Values of tumor markers like CA19-9 and CEA are generally within normal limit in most of the cases reported so far.[24],[25]

According to Nguyen et al.,[29] this plasmacytoid pattern is graded as Gleason pattern 5 and is characterized by high-end stage disease with frequent distant metastasis.

   Conclusion Top

Primary SRCC of prostate is a rare and aggressive variant of prostate adenocarcinoma and strict criteria too are needed to diagnose it clinically, radiologically, and histopathologically as its prognosis is worse than other variants. A thorough GIT work up is required so that metastasis from these common sites is not missed. This rare variant has an aggressive clinical course and a different therapeutic approach is required to manage it.

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.

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Conflicts of interest

There are no conflicts of interest.

   References Top

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Hejka AG, England DM. Signet ring cell carcinoma of prostate: Immunohistochemical and ultrastructural study of a case. Urology 1989;3:155-8.  Back to cited text no. 4
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Derouiche A, Ouni A, Kourda N, Belhadj K, Ben Jilani S, Chebil M. A new case of signet ring cell carcinoma of the prostate. Clin Genitourin Cancer 2007;5:455-6.  Back to cited text no. 16
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Warner JN, Nakamura LY, Pacelli A, Humphreys MR, Castle EP. Primary signet ring cell carcinoma of the prostate. Mayo Clin Proc 2010;85:1130-6.  Back to cited text no. 19
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Correspondence Address:
Iffat Jamal,
IGIMS, Sheikhpura, Patna - 800016, Bihar
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_1045_20


  [Figure 1], [Figure 2]

  [Table 1]


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