A 63-year-old man comes to the office due to intermittent rectal bleeding. The bleeding worsens with defecation and is associated with itchiness. Ten years ago, he had a kidney transplant for diabetic nephropathy and reports compliance with posttransplant immunosuppression medications. Vital signs are normal. Physical examination reveals a 2-cm ulcerated mass extending from the anal verge into the rectum. Biopsy shows large, eosinophilic squamous epithelial cells arranged in islands; cells have hyperchromatic, irregular nuclei, and scant cytoplasm. Significant keratinization is present. Which of the following factors is most likely responsible for the development of this patient's anal lesion?

Question

A 63-year-old man comes to the office due to intermittent rectal bleeding.  The bleeding worsens with defecation and is associated with itchiness.  Ten years ago, he had a kidney transplant for diabetic nephropathy and reports compliance with posttransplant immunosuppression medications.  Vital signs are normal.  Physical examination reveals a 2-cm ulcerated mass extending from the anal verge into the rectum.  Biopsy shows large, eosinophilic squamous epithelial cells arranged in islands; cells have hyperchromatic, irregular nuclei, and scant cytoplasm.  Significant keratinization is present.  Which of the following factors is most likely responsible for the development of this patient's anal lesion?

Quizplus · Accepted Answer

11ec160b_3ad6_31b4_9249_9d21577398bd_MD0001_00 This patient with a history of chronic immunosuppression has perianal bleeding and an ulcerated anal mass. In association with the classic histologic findings, this presentation suggests anal squamous cell carcinoma (SCC). Most patients have rectal bleeding, pain, or pruritus, and examination demonstrates an ulcerated or a nodular, exophytic anal lesion. On histology, SCCs are characterized by large, eosinophilic, hyperchromatic squamous cells with scant cytoplasm arranged in islands. Nuclear atypia and prominent keratinization and/or keratin pearls are usually observed. Anal SCC, as well as multiple other anogenital (eg, cervical, penile, vaginal) and oropharyngeal SCCs, is strongly associated with human papillomavirus (HPV). HPV is a nonenveloped, double-stranded DNA virus that infects cutaneous and mucosal tissues. HPV types 16 and 18 are particularly associated with the development of malignancies. Immunocompromised states (eg, HIV, organ transplant) increase susceptibility to HPV infection and malignant transformation. Other risk factors include smoking, receptive anal intercourse, and female sex. (Choice A) BRAF is a protoonocogene, and mutations are associated with multiple malignancies (eg, melanoma, colon cancer, papillary thyroid cancer) but are not typically associated with anal SCC. (Choice B) Human herpesvirus 8 causes Kaposi sarcoma, an angiogenic tumor that typically occurs in patients with severe immunosuppression (usually AIDS) but can occur in organ transplant recipients. However, it typically involves the extremities, face, or genitalia and results in painless purple or brown lesions. Histologic evaluation demonstrates whorls of spindle cells and neovascularization. (Choice D) Mutations of DNA mismatch repair genes are associated with hereditary nonpolyposis colon cancer (ie, Lynch syndrome), an autosomal dominant disease that results in colonic, endometrial, and ovarian cancer. It is not associated with anal SCC. (Choice E) Poxvirus causes molluscum contagiosum, which is characterized by umbilicated, flesh-colored papules with histologic findings of epidermal hyperplasia and eosinophilic, intracytoplasmic viral inclusions. Although immunocompromised patients are at increased risk of larger lesions, molluscum contagiosum is not associated with malignant transformation. (Choice F) Primary syphilis (caused by Treponema pallidum) can result in a painless, ulcerated anogenital lesion (eg, chancre); however, bleeding is atypical, and dark-field microscopy is used to reveal the presence of spirochetes. Educational objective: Anal squamous cell carcinoma is strongly associated with human papillomavirus and typically presents with rectal bleeding, pruritus, and/or pain; examination demonstrates an ulcerated or nodular, exophytic anal lesion. Histology reveals large, eosinophilic, hyperchromatic squamous cells arranged in islands with nuclear atypia and prominent keratinization. __________ References: Pathology of anal cancer. (http://www.ncbi.nlm.nih.gov/pubmed/27889037) Recent advances in the management of anal cancer. (http://www.ncbi.nlm.nih.gov/pubmed/30345012)

A 63-Year-Old Man Comes to the Office Due to Intermittent