Skip to main content

Colonic medullary carcinoma: an exceedingly rare type of colorectal malignancy: a case report and review of the literature

A Correction to this article was published on 01 November 2023

This article has been updated



Medullary carcinoma of the colon is a rare subtype of colorectal cancer that has a unique, and sometimes varied, clinical and histologic profile. It usually presents in adult patients older than 50 years. Here, we report a unique case of young male patient who initially presented with abdominal pain followed by a large bowel obstruction.

Case presentation

A 40-year-old SriLankan male presented with right-sided abdominal pain and on examination, there was a palpable right iliac fossa mass. Colonoscopy and a computed tomography scan revealed cecal mass. Later, while waiting for elective resection, the patient developed symptoms and signs of a large bowel obstruction. He underwent a laparoscopic right hemicolectomy with an uneventful postoperative course. The histopathologic evaluation of the resected specimens showed invasive carcinoma with syncytial growth pattern, foci of lymphoid host response, and dirty necrosis, in keeping with a medullary carcinoma pT4a pN2b. Unlike most reported medullary carcinoma cases, this patient was young and caudal-related homeobox transcription factor 2 positive.


We have reported another case of medullary carcinoma of the colon in a young patient with unique histologic characteristics. Reporting such cases helps in refine understanding of the histologic and genetic, as well as clinical, phenotypes of medullary carcinoma of the colon.

Peer Review reports


Colorectal cancer (CRC) is the third most common cancer globally and the second most common cause of cancer related mortality, as per the World Health Organization (WHO) factsheet (accessed 6 July 2023). The majority (around 98%) of CRCs are adenocarcinomas [1]. An exceedingly rare (0.29%) subtype is medullary [2] first described in 1999 by Jessurun [3]. Characterized initially by histologically distinct features (undifferentiated high-grade cytology, syncytial growth pattern, and prominent lymphocytic infiltration) followed by correlation with a unique molecular profile (more frequent association with microsatellite instability), it has recently been described to be more common in older individuals and females, with a better outcome when compared with poorly differentiated (usual type) adenocarcinoma [2, 4]. However, due to its rarity, prognostic data are limited and further cases with follow-up are needed to learn more about this rare subtype of adenocarcinoma. There is an increasing interest in the topic recently among clinicians and researchers, with more case reports describing the clinical and pathological features of medullary adenocarcinomas of the colon, in addition to the potential diagnostic and therapeutic approaches [5]. A recent study [7] identified overexpression of key immunoregulatory genes and features that may explain the prognostic difference from usual adenocarcinoma and provide potential therapeutic targets. In this study, we report an unusual case of medullary adenocarcinoma of the colon with some unique characteristics and summarize the reported cases in the literature.

Case report

A 40-year-old male SriLankan presented with a 1 month history of right-sided abdominal pain, loss of appetite, weight loss, and melena, with no family history of gastrointestinal (GI) cancer. On physical examination, there was a palpable mass in the right iliac fossa (RIF) associated with tenderness.

Investigations highlighted hypochromic microcytic anemia [hemoglobin (Hgb) 7.4 mg/dL, hematocrit (Hct) 26%, mean corpuscular volume (MCV) 67 mg/dL, and mean corpuscular hemoglobin (MCH) 19.5 mg/dL]. Tumor markers were normal. Computed tomography (CT) scan of the abdomen and pelvis showed a mass with irregular eccentric soft tissue density involving the cecum and proximal ascending colon measuring 65 × 35 × 31 mm with multiple enlarged regional lymph nodes (Fig. 1). Colonoscopy showed a cecal ulcero-proliferative circumferential lesion with a malignant appearance (Fig. 2). No metastases were seen on the staging CT scan. The patient was scheduled for an elective laparoscopic right hemicolectomy; however, before his date of surgery, he presented to the emergency with an acute obstruction and was taken for emergency surgery. He underwent laparoscopic right hemicolectomy with side-to-side ileocolic anastomosis. The postoperative course was uneventful, and the patient was discharged on the seventh postoperative day.

Fig. 1
figure 1

Computerized scan: mass with irregular eccentric soft tissue density involving the cecum and proximal ascending colon measuring 65 × 35 × 31 mm with multiple enlarged regional lymph nodes

Fig. 2
figure 2

Colonoscopy: cecal, ulcero-proliferative circumferential lesion with a malignant appearance

The histopathology evaluation of the resected specimens showed invasive carcinoma with syncytial growth pattern, foci of lymphoid host response, and dirty necrosis, in keeping with a medullary carcinoma. The tumor was present in subserosal fat (pT4a) and show metastatic carcinoma in 13 (out of 22) lymph nodes (pN2b). There was prominent lympho-vascular invasion. The margins were clear (R0) (Fig. 3). Immunohistochemical stains for mismatch repair (MMR) status showed loss of nuclear expression of both MSH2 and MSH6 with intact expression of MLH1 and PMS2 (Fig. 4). The most commonly reported loss is that of MLH1. The tumor cells expressed CK20 and SATB2 in keeping with a colorectal primary. Unlike most reported medullary carcinoma cases and like usual large bowel cancers, caudal-related homeobox transcription factor 2 (CDX2) was positive. Despite areas with morphological resemblance to endocrine tumor, common neuroendocrine markers (synaptophysin, chromogranin, and CD56) were negative.

Fig. 3
figure 3

Medullary carcinoma showing prominent lymphoid infiltrate (a, b), necrosis characteristic of tumors with microsatellite instability (c, d), syncytial growth pattern with some features that resemble neuroendocrine tumors (e), lymphovascular invasion (f), and lymph node metastasis (g)

Fig. 4
figure 4

Mismatch repair status evaluation using immunohistochemical biomarkers. Loss of MSH2 (MutS homolog 2) and MSH6 (MutS homolog 6) with retained MLH1(MutL homolog 1) and PMS2 (postmeiotic segregation increased 2), confirming microsatellite instability


Medullary carcinoma (MC), a relatively recently identified, extremely rare type of adenocarcinoma (with incidence reported to range from approximately 0.3% to 3%) [2, 6, 7] is characterized by a poorly differentiated carcinoma with a syncytial growth pattern, and with areas that resemble endocrine tumors but lack neuroendocrine marker expression and show a dense lymphoid host response and extensive lymphovascular invasion. So-called dirty necrosis, suggestive of microsatellite instability is also seen, with all tumors showing mismatch repair protein abnormalities. Therefore, these are best classified as a subtype of microsatellite instable carcinoma and may be sporadic or syndromic (Muir–Torre syndrome). Recently, these tumors have been shown to overexpress immunoregulatory genes [8] that, along with dense lymphoid host response, may possibly account for better overall survival when compared with ‘usual’ poorly differentiated adenocarcinoma. Colarossi et al. [9] highlighted immunohistochemical loss of expression of ARID1A along with a higher incidence of BRAF (V600E) mutation. Like other MSI tumors, the mutational burden of these tumors is low. This coupled with overexpression of immunoregulatory genes seems to confer a better prognosis in medullary carcinoma compared with usual-type poorly differentiated adenocarcinoma and may provide unique therapeutic targets. Therefore, correct identification and workup is essential. Especially given that the diagnosis of MC is challenging and can be confused with the diagnosis of other histological subtypes of colon MC, which necessitate a comprehensive pathological examination, in addition to immunohistochemical staining, to confirm the diagnosis of medullary adenocarcinoma of the colon [8, 10].

Table 1 summarizes the key findings in recently published cases of medullary colon cancer based on a review of recent literature on the subject. Around ten cases were found in which the MMR status, the immunohistochemical analysis of the disease, the staging, and the location of the tumor were discussed.

Table 1 The reported cases in the literature

Our patient was a young gentleman diagnosed with cecal adenocarcinoma and regional lymph node involvement. He had an aggressive disease that led to an obstruction that necessitated an urgent surgical resection. Unlike our patient, most cases of colon MC are in older patients, typically over 60 years old (as presented in Table 1), and predominantly in females [3]. Moreover, almost all patients who were diagnosed with colon MC presented with abdominal pain or bleeding per rectum (Table 1) rather than an obstruction.

The histopathological study of the mass showed invasive MC with features resembling neuroendocrine tumors and with only focal areas with dense lymphoid infiltrate. Like most reported cases, there was prominent lymphovascular invasion and a lack of neuroendocrine biomarkers, along with loss of MMR by immunostaining, indicating microsatellite instability. Unlike most reported cases, the tumor cells expressed CDX2 and instead of MLH1 loss, highlighted retained MLH1 and loss of both MSH2 and MSH6. BRAF was not mutated (Table 1). Hence, this case showed that MC can present with different morphological and immunohistochemical patterns and that there are variations in the ‘usual’ molecular signature. Therefore, this expands the diagnostic spectrum of MC and highlights the diagnostic challenges in the absence of an established clinical, molecular, and histopathological pattern for this type of cancer. Reporting rare cases such as colon MC helps clinicians and pathologists with the diagnosis and management of such rare conditions, and can aid in identifying the characteristic of the subtypes of colon cancer and improve our understanding of such rare entities.


Medullary adenocarcinoma of the colon is an exceptionally rare subtype of colorectal cancer, with increasing knowledge about the morphology, immunophenotype and molecular profile. Recent advances in immunohistochemistry and molecular studies played a role in improving the understanding of this subtype. Still, further reports are needed for better understanding of such rare entity. It is therefore imperative that we report cases with comprehensive pathology workup, relevant clinical findings, and follow-up, to add to our understanding of this rare disease.

Data availability

Data are available upon request.

Change history


  1. Ottaiano A, Santorsola M, Perri F, Pace U, Marra B, Correra M, et al. Clinical and molecular characteristics of rare malignant tumors of colon and rectum. Biology. 2022;11(2):267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Jabbal IS, Nagarajan A, Rivera C, et al. Medullary carcinoma of the colon: a comprehensive analysis of the national cancer database. Surg Oncol. 2022;45: 101856.

    Article  PubMed  Google Scholar 

  3. Jessurun J, Romero-Guadarrama M, Manivel JC. Medullary adenocarcinoma of the colon: clinicopathologic study of 11 cases. Hum Pathol. 1999;30(7):843–8.

    Article  CAS  PubMed  Google Scholar 

  4. Knox RD, Luey N, Sioson L, et al. Medullary colorectal carcinoma revisited: a clinical and pathological study of 102 cases. Ann Surg Oncol. 2015;22(9):2988–96.

    Article  PubMed  Google Scholar 

  5. Blakely AM, Nelson RA, Hamilton SA, Lai LL. Sidedness determines clinical characteristics and survival outcomes in medullary adenocarcinoma of the colon. Sci Rep. 2021;11(1):20481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fleming M, Ravula S, Tatishchev SF, Wang HL. Colorectal carcinoma: pathologic aspects. J Gastrointest Oncol. 2012;3(3):153–73.

    PubMed  PubMed Central  Google Scholar 

  7. Pyo JS, Sohn JH, Kang G. Medullary carcinoma in the colorectum: a systematic review and meta-analysis. Hum Pathol. 2016;53:91–6.

    Article  PubMed  Google Scholar 

  8. Friedman K, Brodsky A, Lu S, et al. Medullary carcinoma of the colon: a distinct morphology reveals a distinctive immunoregulatory microenvironment. Mod Pathol. 2016;29:528–41.

    Article  CAS  PubMed  Google Scholar 

  9. Colarossi C, Mare M, La Greca G, De Zuanni M, Colarossi L, Aiello E, et al. Medullary carcinoma of the gastrointestinal tract: report on two cases with immunohistochemical and molecular features. Diagnostics. 2021;11(10):1775.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Rao Bommi J, Kummari S, Lakavath K, Sukumaran RA, Panicker LR, Marty JL, et al. Recent trends in biosensing and diagnostic methods for novel cancer biomarkers. Biosensors. 2023;13(3):398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sharma A, Sharma N, Pantangi P, Sampath P. Medullary adenocarcinoma of colon: distinct entity with a favorable prognosis: 1409. Off J Am Coll Gastroenterol. 2012;107:S561.

    Article  Google Scholar 

  12. Jain S, Jain A, Onizuka N, Boukhar SA. A rare case of medullary carcinoma of the colon presenting as intussusception in an adult with rectal bleeding. Hawaii J Med Public Health. 2014;73(11):348–52.

    PubMed  PubMed Central  Google Scholar 

  13. Cunningham J, Kantekure K, Saif MW. Medullary carcinoma of the colon: a case series and review of the literature. In Vivo. 2014;28(3):311–4.

    PubMed  Google Scholar 

  14. Bağ HK, Kar H, Cin N, Avcı A, Peker Y, Durak E. Colonic medullary carcinoma: a rare case. Istanb Med J. 2017;18(4):251–4.

    Article  Google Scholar 

  15. Martinotti M, Cirillo F, Ungari M, Tanzi G, Rolando G, Tarasconi A, et al. Microsatellite instability in medullary carcinoma of the colon. Rare Tumors. 2017;9(1):6541.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Fatima Z, Sharma P, Youssef B, Krishnan K. Medullary carcinoma of the colon: a histopathologic challenge. Cureus. 2021;13(6): e15831.

    PubMed  PubMed Central  Google Scholar 

  17. Chen IY, Findeis-Hosey JJ, Cannon L, Liao X. Primary colonic medullary carcinoma with exclusive squamous differentiation. Anticancer Res. 2021;41(7):3567–72.

    Article  CAS  PubMed  Google Scholar 

  18. Saikia K. Medullary carcinoma of colon: pathologists dilemma. J Cancer Sci Res. 2023;8(2):532.

    Google Scholar 

Download references


Not applicable.


Open Access funding provided by the Qatar National Library.

Author information

Authors and Affiliations



FA-I: writing—review and editing, writing—original draft. MA-D: conceptualization, writing—review and editing. AT: writing—review and editing. SA: writing—review and editing. SR: writing the pathology part and supplying the pathology slides. MAN: conceptualization, writing—review and editing. MK: conceptualization, writing—review and editing.

Corresponding author

Correspondence to Mahmood Al-Dhaheri.

Ethics declarations

Ethics approval and consent to participate

No institutional review board is needed as there is no direct patient intervention.

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

The authors declare no competing interests.

Additional information

Publisher’s Note

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

The original online version of this article was revised: an error was identified in the Funding section which incorrectly stated there was no funding.

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

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Al-Ishaq, F., Al-Dhaheri, M., Toffaha, A. et al. Colonic medullary carcinoma: an exceedingly rare type of colorectal malignancy: a case report and review of the literature. J Med Case Reports 17, 434 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: