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Subspecialties Histology, Oncology

Case of the Month

A 14-year-old female presents with a firm nodular lesion on the lower lip. She has no significant previous medical history. A representative biopsy of the lesion is shown.

Given the morphologic findings, what is the most appropriate diagnosis?

a. Plexiform neurofibroma
b. Malignant peripheral nerve sheath tumor
c. Plexiform schwannoma
d. Palisaded encapsulated neuroma

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c. Stomach

Primary signet ring cell adenocarcinoma of the colon is a rare subtype of colorectal carcinoma that accounts for less than 1 percent of tumors in the colon and rectum (1). It is most commonly located in the stomach, less frequently in the colon, rectum, gallbladder, bladder, pancreas, or breast (2). Histologic findings include pools of extracellular mucin and the characteristic proliferation of signet ring cells with intracellular mucin displacing nuclei to the periphery. Designation of the subtype requires a morphologic component of 50 percent signet ring cells or greater (3).

Results of a population-based cohort study evaluating all patients diagnosed with colorectal carcinoma in the Surveillance, Epidemiology, and End Results program from 1988 to 2011 indicated a higher rate of signet ring cell adenocarcinoma in patients 20 to 40 years of age (4). The diagnosis has poor survival compared to other histologic subtypes (1), possibly due to late presentation secondary to the absence of screening. A 2011 literature review concluded that signet ring cell adenocarcinoma demonstrates genetic alterations from conventional colorectal carcinoma. Differences included lower KRAS and higher BRAF mutation rates, as well as lower expression of p16 and p53. There was also higher CpG island hypermethylation of tumor suppressor genes and microsatellite instability (5).

Submitted by Erina McKinney, University of Kansas School of Medicine, Kansas City, Kansas; Gang He, American Diagnostic Consultation & Services, New York; and Ting Zhao, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

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  1. R Thota et al., “Clinicopathological features and survival outcomes of primary signet ring cell and mucinous adenocarcinoma of colon: retrospective analysis of VACCR database,” J Gastrointest Oncol, 5, 18 (2014). PMID: 24490039.
  2. UA Almagro, “Primary signet-ring carcinoma of the colon,” Cancer, 52, 1453 (1983). PMID: 6311394.
  3. S Ogino et al., “Distinct molecular features of colorectal carcinoma with signet ring cell component and colorectal carcinoma with mucinous component,” Mod Pathol, 19, 59 (2006). PMID: 16118624.
  4. R Wang et al., “Clinicopathological features and survival outcomes of colorectal cancer in young versus elderly: a population-based cohort study of SEER 9 registries data (1988-2011),” Medicine (Baltimore), 94, e1402 (2015). PMID: 26334895.
  5. V Gopalan et al., “Signet-ring cell carcinoma of colorectum--current perspectives and molecular biology,” Int J Colorectal Dis, 26, 127 (2011). PMID: 20686774.
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