Anatomic pathology selected abstracts

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Editors: Rouzan Karabakhtsian, MD, PhD, professor of pathology and director of the Women’s Health Pathology Fellowship, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Shaomin Hu, MD, PhD, staff pathologist, Cleveland Clinic; S. Emily Bachert, MD, breast pathology fellow, Brigham and Women’s Hospital, Boston; and Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center.

Secondary involvement of the uterine cervix by nongynecologic neoplasms

May 2021—Secondary involvement of the uterine cervix by nongynecologic neoplasms is rare, accounting for less than two percent of metastases to the gynecologic tract. The authors conducted a study to analyze the clinicopathologic features of cervical involvement by nongynecologic malignancies. They identified 47 cases, including 39 (83 percent) carcinomas, six (12.8 percent) lymphomas, and two (4.2 percent) cutaneous malignant melanomas. The most common primary site of origin among carcinomas was the gastrointestinal tract (27; 69.2 percent), followed by the breast and urothelium (five each; 12.8 percent), and gallbladder and lung (one each; 2.6 percent). The gynecologic tract was involved at presentation in 16 (34 percent) patients, including five (10.6 percent) with the cervix as the first site, seven (14.9 percent) with synchronous involvement of the cervix and other gynecologic sites, and four (8.5 percent) with involvement of other gynecologic sites before cervical presentation. Patients with lymphoma tended to be younger than those with carcinoma (43.7 versus at least 50.5 years; P = .01). Mean time to identification of cervical metastases was less than one year for gallbladder carcinoma, melanomas, and gastrointestinal signet ring cell carcinomas (P = .03). Features that varied with different types of metastatic tumor included lymphovascular space invasion, depth of stromal invasion, growth pattern (glands lacking architectural complexity versus complex glands with cribriforming or solid growth), presence of goblet cells and signet ring cells, degree of cytologic atypia, and overall findings mimicking a benign/noninvasive process (P ≤ .027). Six (12.8 percent) tumors were initially misdiagnosed as cervical primary. The authors concluded that metastatic nongynecologic tumors can mimic primary in situ or invasive neoplasms in the ectocervix and endocervix. Knowledge of pertinent clinical history, careful histologic examination, and ancillary studies for targeted biomarkers contribute to accurate diagnosis.

Turashvili G, Samore WR, Oliva E, et al. Secondary involvement of the uterine cervix by nongynecologic neoplasms: a detailed clinicopathologic analysis. Am J Surg Pathol. 2020;44(12):1699–1711.

Correspondence: Dr. Gulisa Turashvili at gulisa.turashvili@sinaihealth.ca

Reproducibility of AJCC criteria for classifying deeply invasive colon cancers

The eighth edition of the American Joint Committee on Cancer’s AJCC Cancer Staging Manual attempts to address ambiguity in the pT category assignment for colon cancer that is present in prior editions. Despite modifications, the distinction between the pT3 and pT4a categories continues to be a source of diagnostic confusion. The authors conducted a study in which they assessed interobserver agreement among pathologists from different institutions in applying AJCC eighth edition criteria for categorizing deeply invasive colonic adenocarcinomas. The authors identified morphologic patterns that produce diagnostic confusion. They assessed 47 colon cancers that closely approached the serosal surface. Six pathologists with interest in gastrointestinal pathology and four focused on other subspecialties classified each case as pT3 or pT4a based on examining low-magnification and high-magnification images of the most deeply invasive area. Interobserver agreement was assessed using Fleiss’ kappa. Cases displayed three morphologic patterns at the advancing tumor edge: continuous invasion through an inflammatory focus, pushing border, and infiltrative glands and cell clusters with serosal reaction. Agreement among gastrointestinal pathologists was slight (κ = 0.21) when inflammation was present at the advancing tumor edge, moderate (κ = 0.46) for cases with a pushing border, and moderate (κ = 0.51) when the advancing edge was infiltrative. Agreement among nongastrointestinal pathologists in cases with inflammatory and pushing invasive fronts was fair (κ = 0.31 and 0.39, respectively), and it was moderate (κ = 0.57) in cases with infiltrative advancing edges. In 10 (21 percent) cases, the distinction between pT3 and pT4a would have changed the overall clinical stage. The authors concluded that histologic criteria for serosal penetration are a persistent source of diagnostic ambiguity for gastrointestinal and general pathologists in the pT categorization of colon cancers. Clarification of these criteria will help ensure uniform reporting of pathologic and clinical stage.

Panarelli NC, Hammer S, Lin J, et al. Reproducibility of AJCC criteria for classifying deeply invasive colon cancers is suboptimal for consistent cancer staging. Am J Surg Pathol. 2020;44(10):1381–1388.

Correspondence: Dr. Nicole C. Panarelli at npanarel@montefiore.org

A study of HIV-positive women with anal high-grade squamous intraepithelial lesions

Women living with HIV are at increased risk for human papillomavirus-associated anal cancer. Given the field effect of human papillomavirus (HPV) pathogenesis, some members of the medical community recommend that anal cancer screening be limited to women living with HIV (WLHIV) who have prior genital disease. The authors conducted a study to characterize the relationship between anal and genital disease in WLHIV to better inform anal cancer screening guidelines. They retrospectively studied 153 WLHIV with biopsy-proven anal high-grade squamous intraepithelial lesions (AHSIL) and long-term evaluable cervical/vaginal/vulvar histopathology. Based on the absence or presence of genital high-grade squamous intraepithelial lesions (HSIL), subjects were categorized as having isolated AHSIL or multicentric HSIL. Demographics, HIV parameters, and cervical/anal HPV status were recorded. The chi-square test was used for bivariate analyses. Of 153 WLHIV with AHSIL, 110 (72 percent) had isolated AHSIL and 43 (28 percent) had multicentric HSIL (28 cervical, 16 vulvar, and eight vaginal HSIL). The median genital surveillance was eight years (range, 1–27 years). Cervical HPV16/18 infection was associated with multicentric disease (P = .001). Overall, 53 percent of multicentric cases presented genital HSIL preceding AHSIL, with a median interval of 13 years (range, 2–23 years). Paired anal and cervical high-risk HPV results were available for 60 women within 12 months of AHSIL diagnosis: 30 (50 percent) had anal infection alone and 30 (50 percent) had anal/cervical coinfection by HPV16/18 (15 percent), non-HPV 16/18 (13 percent), or different types (22 percent). The authors concluded that women living with HIV frequently develop AHSIL without pre-existing genital disease or after long latency following a genital HSIL diagnosis. These findings support anal cancer screening for WLHIV irrespective of prior genital disease.