Hereditary nonpolyposis colon cancer

Tumors with features similar to those of nasopharyngeal carcinoma, so-called lymphoepithelioma-like carcinomas, have been described in several organs but are extremely rare in the colon. We describe a patient with a family history consistent with hereditary nonpolyposis colorectal cancer who had 3 malignant lesions in the right colon, namely, a mucinous cancer, a lymphoepithelioma-like carcinoma, and a well-differentiated adenocarcinoma with prominent lymphoid stroma. To the best of our knowledge, lymphoepithelioma-like carcinoma has not been described previously in hereditary nonpolyposis colorectal cancer. (Arch Pathol Lab Med. 1999;123:720-724)

Lymphoepithelioma-like carcinoma (LELC) is characterized histologically by a syncytial growth pattern of undifferentiated malignant epithelial cells with ill-defined borders, prominent nucleoli, and numerous mitoses, and a prominent stromal and intratumoral lymphoid infiltrate. Lymphoepithelioma-like carcinoma has been described in several organs, including thymus, salivary glands, lung, vagina, tonsil, oral cavity, larynx, skin, cervix,' stomach,2 biliary tract,3 and urinary bladder.4 Many LELCs, especially those of the stomach and salivary glands, are associated with Epstein-Barr virus (EBV).

Sporadic colorectal carcinomas (CRCs) are generally well-differentiated or moderately well-differentiated adenocarcinomas.5 The much less common undifferentiated CRCs include the small cell (neuroendocrine)" and solid or medullary7 variants. The latter form, which shares some histologic features with LELC, occurs relatively more frequently in hereditary nonpolyposis colorectal cancer (HNPCC) (Lynch syndrome)9 than in a sporadic setting. To our knowledge, however, LELC proper has not been described in HNPCC.

We report here a case of LELC of the ascending colon in a 46-year-old man who had an apparent HNPCC family background. This carcinoma was accompanied by 2 additional carcinomas, 1 of which, we hypothesize, may represent a precursor of the LELC.

REPORT OF A CASE

A 44-year-old African-American man with an unremarkable medical history was admitted to Roger Williams Hospital, Providence, RI, with complaints of abdominal pain and weight loss for 8 months. His family history was significant for colorectal cancer in his mother at the age of 42 years and of endometrial cancer in his sister, who died of this disease at the age of 34 years. His 3 children, his 4 brothers, and another sister were apparently in good health.

Physical examination revealed a palpable right upper quadrant mass. Laboratory studies showed an increased carcinoembryonic antigen level (6.2 (mu)g / L) and hypochromic microcytic anemia due to iron deficiency. Computed tomographic scan and magnetic resonance imaging of the abdomen showed marked thickening of the wall of the transverse colon, with adjacent mesocolic fat infiltration suggestive of spread from a colonic cancer. No evidence of metastases or lymphadenopathy was found. Colonoscopy could not proceed beyond a stenosing tumor mass at the hepatic flexure. A biopsy of the mass was taken and was diagnosed as poorly differentiated adenocarcinoma.

At surgery, a large mass extended from the hepatic flexure of the colon to the anterior surface of the duodenum and to the head of the pancreas. There was no evidence of tumor implants in the abdominal cavity, and the liver appeared unremarkable. The patient underwent right hemicolectomy. Recovery was uneventful and the patient completed a 6-month course of chemotherapy with 5 fluorouracil and leucovorin calcium. Three months after the colectomy was performed, a pedunculated adenomatous polyp with adenocarcinoma extending into the submucosa of the stalk was removed endoscopically from the rectum.

Because of the family history and the pathologic features of the colonic neoplasia, the patient was believed to be affected by HNPCC and was referred to a center for hereditary gastrointestinal cancer for counseling and genetic testing (A. K. Rustgi, director, Massachusetts General Hospital, Boston, Mass). The diagnosis of HNPCC was confirmed; however, the patient refused genetic testing. His sister underwent hysteroscopy, which was negative. One brother had a colonoscopy, which revealed no lesions. The patient remained free of disease 7 months after surgery.

METHODS

The formalin-fixed specimens were embedded in paraffin, sectioned at 6 Jim, and stained with hematoxylin-eosin, periodic acid-Schiff following diastase digestion, and Alcian blue (pH 2.5). Immunohistochemical stains were performed on paraffin-embedded sections using the following commercial antibodies with the avidin-biotin-peroxidase technique: Cam 5.2 (Becton Dickinson, Mountain View, Calif), AEl/AE3 (Boehringer-Mannheim, Indianapol.is, Ind), CD3 (Dako Corporation, Carpinteria, Calif), L26 (BioGenex, San Ramon, Calif), S100 protein (Dako), synaptophysin (BioGenex), chromogranin (Boehringer-Mannheim), neuronspecific enolase (BioGenex), Bcl-2 (Dako), p53 (Dako), and latent membrane protein-1 (Dako). RNA in situ hybridization for EBV was used following the method described in detail elsewhere.10 In brief, a 30-base pair oligonucleotide complementary to a segment of the EBV-encoded RNA-1 (EBER-1) gene was used. Tenmicrometer sections from paraffin-embedded tissue were deparaffinized, dehydrated, digested with pronase, and hybridized overnight using a biotinylated EBER-1 probe at a concentration of 0.26 (mu)L/mL of probe Detection was achieved using avidinalkaline phosphatase conjugate followed by development of signal using diaminobenzidine as the chromogen. A brown-black nuclear signal above background levels was scored as a positive reaction. RNA integrity was determined by detection of the ubiquitous U6 (a transcript of RNA polymerase III present in high levels in the cells) signals. Only sections showing hybridization signal with the U6 probe were determined to be adequate for analysis with the EBER-1 probe. Appropriate positive and negative controls were tested concurrently. Polymerase chain reaction assay for EBV was performed according to Kahn et.11 In brief, DNA was isolated from paraffin-embedded tissue sections and annealed with oligonucleotide primers complementary to the EBV BZLF gene. After 35 amplification cycles, the product was detected applying an aliquot of the polymerase chain reaction to an agarose gel for electrophoresis. A positive result was judged by the presence of a discrete 286-base pair band after ethidium bromide and UV light exposure. Positive and negative control reactions were included.

PATHOLOGIC FINDINGS