Skip to main content

Signet ring cell carcinoma of rectum metastasizing to synchronous renal cell carcinoma: a case report



Rectal signet ring cell carcinoma is a rare type of colorectal adenocarcinoma characterized by an aggressive biological behavior and poor prognosis. The co-occurrence of colorectal carcinoma and renal cell carcinoma (RCC) has found in many hundreds of patients, many of whom also have additional malignancies. Cancer to cancer metastasis is rare and an uncommon phenomenon in malignancy, especially at the time of initial diagnosis, suggesting a genetic susceptibility.

Case presentation

We present the case of a 66-year-old Macedonian man with synchronous rectal signet ring cell carcinoma and RCC with tumor to tumor metastasis feature. He underwent a left nephrectomy and anterior rectal resection after complaining of constipation for 3–4 months and the appearance of synchronous tumors on the imaging studies. Morphology and immunohistochemical analysis of specimens from the RCC revealed signet ring cells identical to the rectal signet ring cell carcinoma. The next-generation sequencing study revealed mutations in TP53 and ERBB2, and microsatellite stable signet ring cell carcinoma was determined by deoxyribonucleic acid (DNA) sequencing.


Cancer to cancer metastasis, although rare, needs to be considered in synchronous tumors. RCC, when diagnosed in multiple synchronous tumors, should be examined carefully. The paucity of reported cases indicates the need for advanced research in imaging methods for metastasis and new therapeutic approaches.

Peer Review reports


Primary signet ring cell carcinoma of the rectum (PSRCCR) is a rare variant of colorectal adenocarcinoma (AC) with an incidence of less than 1% [1]. It is diagnosed on the basis of the tumor containing > 50% of cells that contain prominent intracytoplasmic mucin with marked nuclear displacement and molding (signet ring cells). The most common site of such tumors is the stomach with the characteristic feature of linitis plastica. Presentation usually occurs at an advanced stage, and the tumor has a distinctive molecular pattern and poor prognosis [2, 3].

Reported data suggest a rare but strong association between gastrointestinal and urogenital tumors based on synchronous appearance. Cancer to cancer metastasis is defined as metastasis in histologically separate carcinomas. The synchronous occurrence of colorectal AC with renal cell carcinoma (RCC) is a rare development, with an incidence of 0.4–4.8%, but AC to RCC metastasis at initial diagnosis has been reported in fewer than five cases. To our knowledge, we report here the first reported case of RSRCCR with metastasis to RCC.

Case presentation

A 66-year-old Macedonian male presented with symptoms of constipation and blood in the stool (hematochezia) for 3–4 months before seeing a gastroenterologist. Review of his medical records revealed no family history of note. The outer anal examination revealed old thrombosed hemorrhoids, and endoscopy revealed an obstructive neoplastic mass located 5–7 cm from the anus. The tumor tissue showed diffuse ulcerations and bled when touched. Eight biopsy specimens were taken for pathohistological examination. The diagnosis of mucinous AC with signet ring cells was made. Radiographic examination showed no pathological findings in the liver, pancreas, spleen and lungs, but revealed a tumor mass in the left lower kidney pole with infiltrating border that caused compression to the collector system. Preoperative computed tomography confirmed synchronous tumors in the kidney and rectum (Fig. 1). The patient was admitted to the University Clinic of Abdominal Surgery in Skopje for surgical treatment. Laboratory tests showed elevated values for the enzymes lactate dehydrogenase (612 U/L), alkaline phosphatase (387 U/L) and C-reactive protein (up to 45.7 mg/L). A medial laparotomy was performed, with surgical resection of the anterior rectal area, simultaneously with left nephrectomy. Carcinosis in the small pelvis was observed.

Fig. 1

Computed tomography scan showing synchronous tumors (within green circles). a Kidney tumor in lower pole, b Rectal tumor mass with luminal narrowing

Tissue samples were analyzed at the Institute of pathology, Faculty of Medicine in Skopje. Gross rectal examination of tissue specimens showed a rectal tumor measuring 5.5 cm infiltrating into the perirectal fat. The kidney contained a yellowish round tumor measuring 5 cm, with necrosis and hemorrhage. The adrenal gland was slightly enlarged into perirenal fat. The tissue specimens were fixed in formalin, embedded in Paraffin and routinely stained with hematoxylin & eosin stain. Microscopic analysis revealed PSRCCR with nodal metastasis, lymphatic and vascular tumor emboli and uncommon metastasis to synchronous RCC and to the adrenal gland (Fig. 2). The tumor was classified as Stage IV according to the pTNM/UICC staging system. All specimens were analyzed immunohistochemicaly with CK20, CDX2, vimentin, RCC, E-cadherin and the mismatch repair (MMR) proteins MLH1, MSH2, MSH6 and PMS2. Signet ring cells were positive for CDX2 and CK20 (Table 1). The absence of expression of E-cadherin in the metastasized cells indicated that they were the same as those in the primary carcinoma (Fig. 3).

Fig. 2

Microscropic images of signet ring cell carcinoma (hematoxylin & eosin stain). Black arrow indicates signet ring cells a Primary tumor in rectum (magnification: × 100). b Metastasis in renal cell carcinoma (RCC); red arrow indicates RCC (magnification: × 100). c Metastasis in adrenal gland; blue arrow indicates metastasis in adrenal gland (Magnification: × 50). Black arrow indicates signet ring cells, red arrow indicates RCC and blue arrow indicates adrenal gland

Table 1 Immunohistochemical analysis of renal cell carcinoma, rectal signet ring cell carcinoma and signet ring cell component in renal cell carcinoma
Fig. 3

Immunohistochemistry results showing identical expression in the primary and metastatic components of the signet ring cells in RCC. a CK20 rectum (magnification: × 100). b CDX-2 rectum (magnification: × 50). c E-cadherin rectum (magnification: × 100). d CK20 RCC (magnification: × 100). e CDX-2 RCC (magnification: × 100). f E-cadherin RCC (magnification: × 200)

There was nuclear expression only of MMR protein MSH6, whereas the MMR proteins MLH1, MSH2 and PMS2 showed loss of the nuclear signal (Fig. 4). Therefore, the tumor was further analyzed molecularly using the ABI 310 DNA analyzer (Applied Biosystems, Foster City, CA, USA), which revealed a microsatellite stable (MSS) tumor. Molecular analysis showed mutations in TP53 and ERBB2, as determined by next-generation sequencing of AKT1, BRAF, EGFR, ERBB2, FOXL2, GNA11, GNAQ, KIT, KRAS, MET, NRAS, PDGFRA, PIK3CA, RET and TP53. The patient died a few months after surgical treatment.

Fig. 4

Immunohistochemistry for mismatch repair proteins, with only MSH6 showing nuclear expression (magnification: × 400), a MSH6, b MLH1, c MSH2, d PMS2


Primary rectal signet ring cell carcinoma

PSRCCR is a variant of colorectal cancer (CRC) with a rare, aggressive presentation and diagnosis at an advanced stage. It is more common in young adults than in older patients and has distinct molecular profiles, such as microsatellite instability and BRAF mutations [3,4,5,6]. Our case presented a microsatellite stable (MSS) tumor without BRAF activating mutations. A stomach origin was excluded in earlier examinations because this type of carcinoma usually presents as gastric carcinoma. Signet ring cells present a large amount of cytoplasmic mucin displacing the nuclei at the periphery. CT scan or radiologic imaging is part of the initial examination in patients with abdominal pain or other long-term symptoms of discomfort. The most common metastatic site is peritoneal seeding; there is a low incidence in the liver, lung and bone, with uncommon metastatic sites also in the vertebrae, extraocular muscles, bone marrow and skin [7,8,9,10,11]. Because of the rare occurrence, the clinical importance of PSRCCR is difficult to evaluate, but the poor prognosis is evident and accompanied by many synchronous and metachronous distant organ metastasis.

Association with renal cell carcinoma

A few but strong studies have shown the occurrence of synchronous gastrointestinal and kidney tumors [12,13,14]. In their study of 101 patients, Steinhagen et al. emphasized the occurrence of both CRC and RCC, with a risk for additional malignancies [12]. RCC was observed at the median age of 67 years and was mainly of the clear cell type, with half of the cases found during the workup for CRC [12]. Our case also indicates an incidental finding of a kidney tumor during the colorectal imaging analysis. In their immunochemistry study, Steinhagen et al. found that an MMR protein was absent in one in ten patients with CRC, but the accompanying RCC retained all four proteins [12]. Our case showed nuclear loss of MLH1, MSH2 and PMS2 on immunohistochemistry, with DNA sequencing for microsatellite instability revealing that the tumor was MSS. A search of the PubMed library did not find a synchronous case of RSRCC with RCC, as presented in our patient.

Tumor to tumor metastasis

The third rare event in our case was the tumor to tumor metastasis phenomenon. There must be at least two separate and histologically different neoplasms to confirm the feature. Why certain tumors are donors and some are recipients is a question that is open to debate. RCC is considered to be a well-documented recipient of metastasis by lung carcinomas, prostatic carcinomas, breast carcinomas, stomach adenocarcinomas, thyroid anaplastic carcinomas and uterine adenocarcinomas [15,16,17,18]. The vascularity or donor genetics of the recipient tumor might be the key to determining this metastatic pattern. Colorectal AC is reported to be able to metastasize to ovarian cystadenofibroma [17]. Sakai et al. reported a signet ring cell carcinoma of the stomach with metastasis into RCC after 6 years [18]. Our case presented metastasis in RCC of PSRCCR at initial diagnosis. Imaging techniques are unreliable on early detection of metastasis, and time is needed as well as histopathology examinations for confirmation.


We present a case of signet ring cell carcinoma of rectum with metastasis to synchronous RCC and to the adrenal gland. RCC when diagnosed in multiple synchronous tumors should be examined carefully. Cancer to cancer metastasis as a rare phenomenon that needs to be considered in synchronous tumors. The paucity of reported cases indicates the need for advanced research in imaging methods for the detection of metastasis and new therapy approaches.

Availability of data and materials

Not available.





Colorectal cancer




Primary signet ring cell carcinoma of the rectum


Renal cell carcinoma


  1. 1.

    Belli S, Aytac HO, Karagulle E, Yabanoglu H, Kayaselcuk F, Yildirim S. Outcomes of surgical treatment of primary signet ring cell carcinoma of the colon and rectum: 22 cases reviewed with literature. Int Surg. 2014;99(6):691–8.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Liang Z, Yan D, Li G, Cheng H. Clinical analysis of primary colorectal signet-ring cell carcinoma. Clin Colorectal Cancer. 2018;17(1):e39–44.

    Article  PubMed  Google Scholar 

  3. 3.

    Nitsche U, Zimmermann A, Späth C, et al. Mucinous and signet-ring cell colorectal cancers differ from classical adenocarcinomas in tumor biology and prognosis. Ann Surg. 2013;258(5):775–83.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Park PY, Goldin T, Chang J, Markman M, Kundranda MN. Signet-ring cell carcinoma of the colon: a case report and review of the literature. Case Rep Oncol. 2015;8(3):466–71.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Mora-Guzmán I, Di Martino M, Muñoz de Nova JL, Viamontes Ugalde FE, Rodríguez Sánchez A. Carcinoma primario de colon con células en anillo de sello: una rara entidad de mal pronóstico. Comunicación de 2 casos. Revista de Gastroenterología de México. 2018;83:358–60.

    Article  Google Scholar 

  6. 6.

    Hirata Y, Kanno K, Kishikawa N, et al. Primary signet ring cell carcinoma of rectum diagnosed by boring biopsy in combination with endoscopic mucosal resection. Case Rep Med. 2018;2018:5860815.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Kilickap S, Aksoy S, Dinçer M, Saglam EA, Yalçin S. Cutaneous metastases of signet cell carcinoma of the rectum without accompanying visceral involvement. South Med J. 2006;99(10):1137–9.

    Article  PubMed  Google Scholar 

  8. 8.

    Morales-Cruz M, Salgado-Nesme N, Trolle-Silva AM, Rodríguez-Quintero JH. Signet ring cell carcinoma of the rectum: atypical metastatic presentation. BMJ Case Rep. 2019;12(4):e229135.

    Article  PubMed  Google Scholar 

  9. 9.

    Mandzhieva B, Jalil A, Nadeem M, Hasan SA, Jain AG. Most common pathway of metastasis of rectal signet ring cell carcinoma to the skin: hematogenous. Cureus. 2020;12(2):e6890.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Singh K, Singh A, Bhutra S, Pachori G, Jangir MK. Metastatic primary signet ring cell carcinoma of rectum: a case report of 10-year-old male child. J Clin Diagn Res. 2014;8(2):177–8.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Farraj FA, Sabbagh H, Aridi T, Fakhruddin N, Farhat F. Signet ring cell carcinoma of the colon in young adults: a case report and literature review. Case Rep Oncol Med. 2019;2019:3092674.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Steinhagen E, Moore HG, Lee-Kong SA, et al. Patients with colorectal and renal cell carcinoma diagnoses appear to be at risk for additional malignancies. Clin Colorectal Cancer. 2013;12(1):23–7.

    Article  PubMed  Google Scholar 

  13. 13.

    Melichar B, Morávek P, Ferko A, Podhola M. Metastatic colorectal carcinoma and kidney tumors: a report of four cases. Tumori. 2010;96(3):483–6.

    Article  Google Scholar 

  14. 14.

    Piao J, Friedman P, Siddiqui S, Veerapong J, Lai JP. Synchronous type 1 papillary renal cell carcinoma in a patient with rectal adenocarcinoma. Anticancer Res. 2016;36(9):4821–4.

    Article  PubMed  Google Scholar 

  15. 15.

    Samankan S, Aghighi M, Krabill K, Azabdaftari G. Tumor-to-tumor metastasis in synchronous primary kidney and colon tumors. Cytol Histol Rep. 2018.

    Article  Google Scholar 

  16. 16.

    Lakovschek I, Petru E, Pollheimer MJ, et al. A rare case of cancer-to-cancer metastasis: breast cancer to renal cell cancer. Wien Med Wochenschr. 2019;169:350–3.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Fahoum I, Brazowski E, Hershkovitz D, Aizic A. Tumor-to-tumor metastasis of colorectal adenocarcinoma to ovarian cystadenofibroma: a case report and review of the literature. Int J Gynecol Pathol. 2020;39(3):270–2.

    Article  PubMed  Google Scholar 

  18. 18.

    Sakai Y, Kanomata N, Itami H, Kajimoto K, Sakuma T, Ohbayashi C. Signet-ring cell carcinoma of the stomach metastasizing to renal cell carcinoma: a case report and review of the literature. Kobe J Med Sci. 2010;55(6):E122–31.

    PubMed  Google Scholar 

Download references




No funding or commercial intent.

Author information




BK and BI performed the histologic and immunohistochemical examination and analyzed the data. RJ, SKK and AE performed the molecular analysis and interpreted the results. BO and DHM performed the surgical intervention and obtained the clinical data. BK and SKK made the major contributions to the design, concept and writing of the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Blagica Krsteska.

Ethics declarations

Ethics approval and consent to participate

Written consent was obtained from the patient and the report follows the recommendations of Ethics Board of Faculty of Medicine in Skopje.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

All authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Krsteska, B., Jovanovic, R., Eftimov, A. et al. Signet ring cell carcinoma of rectum metastasizing to synchronous renal cell carcinoma: a case report. J Med Case Reports 15, 123 (2021).

Download citation


  • Case report
  • Rectal
  • Signet ring cell carcinoma
  • Tumor to tumor metastasis
  • Renal cell carcinoma