| Abstract|| |
Small intestinal medullary carcinoma (MC) is a newly recognized subclass of small intestinal carcinomas and is an exceptional entity for this site. A search of the literature for similar cases arising in the small intestine revealed only six previously reported cases. Here we present a case of MC arising in the jejunum of a 65-year-old male. The patient presented to the emergency with features of perforation peritonitis with liver metastasis and no known predisposing factors like inflammatory bowel disease and celiac disease. Studies conducted on this tumor's colonic counterpart have shown microsatellite instability (MSI) and B-type Raf kinase (BRAF) mutations; however, few exceptions are known. Also, this subtype of carcinoma is known to have a better prognosis than its other histological subtypes.
Keywords: Intestinal perforation, jejunal carcinoma, liver metastasis, medullary carcinoma, small intestine
|How to cite this article:|
Talwar A, Ahuja A, Phulware RH. Medullary carcinoma of jejunum presenting as perforation peritonitis: A case report. Indian J Pathol Microbiol 2022;65:679-82
|How to cite this URL:|
Talwar A, Ahuja A, Phulware RH. Medullary carcinoma of jejunum presenting as perforation peritonitis: A case report. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Aug 15];65:679-82. Available from: https://www.ijpmonline.org/text.asp?2022/65/3/679/351604
| Introduction|| |
Small bowel cancers account for less than 3% of the gastrointestinal tract cancers, of which adenocarcinoma comprises the bulk. Medullary carcinoma (MC) is a newly diagnosed, extremely rare histopathological subgroup of adenocarcinoma. It was reported and sketched for the first time by Gibbs et al. and was recently included in the WHO blue books as a separate entity. It has been mainly described and studied in the colon. On review of the literature, we could find only six reported cases of (from 2011 to 2019) medullary carcinoma of the small intestine.
| Case History|| |
A 65-year-old male with no known co-morbidities presented to the surgical emergency department with perforation peritonitis and hypotension features. The patient did not have any significant past medical history or surgery or chronic illness. An exploratory laparotomy with resection of part of jejunum with tumor and excision biopsy of liver metastases was done, which revealed a perforation at the anti-mesenteric border of the jejunum along with multiple liver deposits. Grossly, the small intestine was 45 cm in length with a sizeable serosal perforation, along with numerous tumor nodules ranging from 1 × 1 cm to 4 × 3 cm. The intestinal lumen showed a large circumferential tumor measuring 7 × 7 × 5 cm, perforating the serosa, and infiltrating into the mesentery. A cut section of the tumor was grayish-white, soft to firm with areas of necrosis [Figure 1]a and [Figure 1]b. The resected margins were free of tumors.
|Figure 1: (a and b) - Gross image showing a grayish-white tumor in the lumen of the small intestine (jejunum). (c) - The hematoxylin and eosin (H&E × 40) section shows intestinal mucosa with sub-epithelium having a large tumor in syncytial and nodular growth pattern with pushing borders. (d and e) - Higher magnification (H&E × 400) shows tumor cells having marked nuclear pleomorphism, vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm and exhibiting prominent infiltration by lymphocytes. Numerous tumor-infiltrating lymphocytes are also present. (f) - Marked nuclear pleomorphism (H&E × 400)|
Click here to view
Microscopy of the tumor revealed numerous sheets of malignant cells. These individual tumor cells have moderate to severe nuclear atypia, vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. The intervening tumor areas showed prominent infiltration by lymphomononuclear cells (lymphocytes). This tumor showed invasion through the muscularis propria into the surrounding jejunal fibro adipose tissue [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f. Based on the histomorphology, the differential diagnosis of MC or poorly differentiated adenocarcinoma or neuroendocrine carcinoma of the small intestine was kept, and an immunohistochemical (IHC) panel was applied. The tumor cells were diffusely positive for pancytokeratin [Figure 2]a, and focally for CK-7 [Figure 2]b and epithelial membrane antigen (EMA), while negative for CK-20 [Figure 2]c. Ki-67% index was high, about 80% [Figure 2]d. The tumor cells were negative for synaptophysin [Figure 2]e, cluster of differentiation (CD) 56, chromogranin [Figure 2]f, CDX2 [Figure 2]g, and desmin [Figure 2]h. Five of the nine (5/9) lymph nodes examined showed tumor metastasis in them along with soft tissue tumor deposits. Based on the histomorphology and IHC profile, a concluding diagnosis of high-grade MC of the jejunum with vascular and lymphatic invasion pT4pN2pM1 was rendered. However, the patient died on the second postoperative day due to postsurgical complications. No medical oncologist referral was done.
|Figure 2: The tumor cells were immunopositive for pancytokeratin (PANCK) (a), CK-7 (b), immunonegative for CK20 [positive control - normal intestinal epithelium in left upper corner] (c). Ki-67 shows approximately > 80% proliferative activity (d). The tumor cells are immunonegative for neuroendocrine markers such as synaptophysin (e) and CD56 (f), along with CDX-2 (g) and desmin (h)|
Click here to view
| Discussion|| |
MC is extremely rare in both the small and large intestines. Thirunavukarasu et al. (1973–2006) studied MC cases using the Surveillance, Epidemiology, and End Results (SEER) database. They observed that the occurrence of colonic MC is exceptionally uncommon (0.005% to 0.008%) and has unique clinical, demographic, and histological characteristics. It occurs more frequently in the seventh decade of life with female predominance (2:1).
Approximately 10% of the patients with medullary carcinoma (MC) colon have shown metastasis at the time of diagnosis either in the form of regional lymph node metastasis or local invasion. Metastasis to liver is exceptionally rare., Our case showed metastasis to five out of nine regional lymph nodes and to the liver (stage IV).
The most common presentation was abdominal pain due to obstruction; however, one case presented with intussusception and an ulcerated tumor. The most common site of the tumor was the jejunum, followed by the ileum.,,, Chronic underlying inflammatory bowel diseases such as ulcerative colitis, celiac, or Crohn's disease are major contributing factors to its pathogenesis. Reviewing the literature for the small intestine, two cases associated with Crohn's disease and one case had a history of celiac disease. The rest of the carcinomas did not reveal a record of any chronic inflammatory diseases, similar to our case.,,,
According to Winn et al., MC of the colon keeps a significant degree of intestinal differentiation as evidenced by its high percentage of immunopositive staining for (mucin 1, cell surface-associated) MUC-1 (67%), MUC-2 (60%), and (trefoil factor 3) TFF-3 (53%). Also, immunopositivity of calretinin (73%), and loss of (Mut L homolog 1) MLH-1 (21%) and (homeobox transcription factor) CDX2 (19%) may help to differentiate MC from poorly differentiated carcinoma of the colon. However, colorectal MC shows an aberrant IHC pattern with loss of CDX2 and CK20.,, Major differentials considered for this tumor were undifferentiated carcinoma and neuroendocrine carcinoma. Morphological features, along with a lack of neuroendocrine IHC markers, helped us to diagnose the case as MC of the small intestine.
MC frequently contains microsatellite instability (MSI), most frequently in a combination of BRAF mutations. The presence of MSI imparts an overall better prognosis to this tumor compared to the other adenocarcinoma histologic subtypes.,,,
According to the National Comprehensive Cancer Network (NCCN), guidelines recommend treating small intestinal adenocarcinomas for local disease, segmental resection of the small bowel is the mainstay of treatment, though duodenal tumors may require either pancreaticoduodenectomy or segmental duodenal resection along with dissection of >8 lymph node has shown significantly improved outcome.,,,, However, most patients with metastatic small bowel adenocarcinoma (SBA) are treated with systemic therapy. Systemic therapy options include fluoropyrimidine-based chemotherapy, taxane-based chemotherapy, or checkpoint inhibitors.,,,, NCCN recommendations for adjuvant therapy are 6 months of adjuvant treatment with 5-fluorouracil and oxaliplatin (FOLFOX), capecitabine plus oxaliplatin (CAPEOX), 5-fluorouracil plus leucovorin (5-FU/LV), or capecitabine for any locally advanced SBA with positive lymph nodes (stage III). While for stage II tumor, observation or 6 months of adjuvant treatment with FOLFOX, CAPEOX, 5-FU/LV, or capecitabine, microsatellite stable (MSS) or DNA mismatch repair (MMR) proficient (pMMR) and have high-risk features. Observation after surgical treatment of all stage I tumors and for stage II tumors that are microsatellite instability-high (MSI-H) or DNA mismatch deficient (dMMR). Stage III and IV carcinomas have been shown to benefit from adjuvant chemotherapy for 3–6 months duration.,, After an extensive literature search for MC of the small intestine, only six reported cases could be found. The table below gives details of the same [Table 1].
| Conclusion|| |
Despite the rarity of this entity in the small intestine, having a better prognosis than its morphological differentials make it a vital commodity to be considered. It is clear from the lack of extensive data that additional diagnostic and treatment studies need to be conducted; till then, the treatment of this entity will remain inconsistent due to a lack of standardized diagnostic criteria.
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|| |
Nagtegaal ID, Odze RD, Klimstra D et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76:182-88.
Gibbs NM. Undifferentiated carcinoma of the large intestine. Histopathol 1977;1:77-84.
Thirunavukarasu P, Sathaiah M, Singla S, Sukumar S, Karunamurthy A, Pragatheeshwar K, et al
. Medullary carcinoma of the large intestine: A population-based analysis. Int J Oncol 2010;3:901-07.
Brcic I, Cathomas G, Vanoli A, Jilek K, Giuffrida P, Langner C. Medullary carcinoma of the small bowel. Histopathol 2016;69:136-40.
Lanza G, Gafa R, Matteuzzi M, Santini A. Medullary-type poorly differentiated adenocarcinoma of the large bowel: A distinct clinicopathologic entity characterized by microsatellite instability and improved survival. J ClinOncol 1999;17:2429-38.
Peycru T, Jarry J, Soubeyran I. Sporadic medullary carcinoma of the ileum. Clin Gastro enterol Hepatol. 2011;9:24. doi: 10.1016/j.cgh. 2011.03.006.
Slack D, Sachidananda S, Zdankiewicz P. Synchronous medullary carcinomas of the small bowel presenting as recurrent small bowel obstruction. Surg Open Acc 2019;1:3.
Winn B, Tavares R, Fanion J, Noble L, Gao J, Sabo E, Resnick MB. Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation. Human Pathol 2009;40:398-04.
Jessurun J, Romero-Guadarrama M, Manivel C. Medullary adenocarcinoma of the colon: Clinicopathologic study of 11 cases. Hum Pathol1999;30:843-8.
Benson AB, Venook AP, Al-Hawary MM, Arain MA et al
. Small bowel adenocarcinoma, version 1.2020, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2019;17:1109-33.
Ravi H Phulware
Assistant Professor, Department of Pathology and Laboratory Medicine, Level-3, Medical Teaching Block, All India Institute of Medical Sciences (AIIMS), Rishikesh - 249 203, Uttarakhand
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]