More Than Meets the Eye: High-Grade Neuroendocrine Carcinoma with Glandular Features of the Anorectum in a Patient with HIV

Background

Neuroendocrine carcinoma (NEC) of the colorectum can be histologically indistinguishable from poorly differentiated adenocarcinoma on routine hematoxylin and eosin staining. People with HIV carry an increased risk of HPV-associated anorectal disease, which may produce multifocal, atypical anorectal neoplasms. Because high-grade NEC is managed with a different chemotherapy backbone than conventional colorectal adenocarcinoma, accurate classification carries immediate therapeutic consequences.

Case Presentation

41-year-old male with HIV, HPV-associated perianal condylomata, and a 7-month lapse in antiretroviral therapy presented with rectal pain and bleeding, difficulty defecating, and approximately 30 pounds of weight loss. Cross-sectional imaging showed concentric rectosigmoid wall thickening with perirectal and left external iliac lymphadenopathy and multiple hypodense hepatic lesions. MRI demonstrated an ill-defined lower rectal mass extending to the anorectal junction with mesorectal fat infiltration and abutment of the anterior mesorectal fascia. Colonoscopy revealed an ulcerated, cratered mass at the anal verge with adjacent perianal warts. Initial rectal biopsy demonstrated synaptophysin and chromogranin positivity with a Ki-67 of 100%, supporting high-grade NEC. The liver biopsy showed focal CK7 positivity, CK20 negativity, and SATB2/Villin positivity, consistent with metastatic adenocarcinoma of colorectal origin. The patient received modified FOLFOX6, later with bevacizumab, and underwent diverting colostomy for obstructive symptoms. Four months later, repeat IHC of the liver specimen showed synaptophysin and chromogranin positivity, while repeat IHC of the rectal lesion showed CK7 positivity and CK20 negativity — reclassifying the liver lesion as high-grade NEC of colorectal origin. Because both lesions retained adenocarcinoma features alongside neuroendocrine findings, the regimen was not modified at reclassification, transitioning to platinum/etoposide only after an additional four months. The course was complicated by malignant hypercalcemia, hyponatremia, colostomy malfunction, and severe sepsis. Restaging showed progressive hepatic metastases, new pulmonary nodules, enlarging pelvic adenopathy, and a new neck lesion, with a CEA of 122. Given rapid progression, the patient transitioned to hospice care.

Findings

The main critical finding in this case are primary and metastatic sites containing overlapping neuroendocrine and glandular features, thus delaying recognition and appropriate treatment of the correct diagnosis.

Discussion & Conclusion

This case illustrates the diagnostic ambiguity that arises when a poorly differentiated anorectal tumor shows concurrent neuroendocrine and glandular features, raising the differential of NEC versus adenocarcinoma with neuroendocrine differentiation versus mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN). Emerging data implicate HPV in a subset of anorectal neuroendocrine and mixed neoplasms, supporting consideration of multifocal HPV-associated disease in people with HIV presenting with anal masses. Neuroendocrine and adenocarcinoma IHC of both primary and metastatic sites is essential when selecting a chemotherapy backbone. Discordant histology within a mass, or between primary and metastatic sites, should prompt component quantification alongside molecular profiling, with reclassification triggering urgent therapy reconsideration rather than deferred adjustment.