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.

Use of PRAME in distinguishing nodal nevi from metastatic melanoma

December 2020—It can be difficult to distinguish metastatic melanoma from melanocytic nevi in lymph nodes. Because diffuse IHC PRAME (preferentially expressed antigen in melanoma) expression is detected in the majority of primary and metastatic melanomas, but rarely in nevi, the authors conducted a study in which they hypothesized that PRAME could be a useful adjunct marker for the diagnosis of melanocytes in lymph nodes. They examined 45 nodal melanocytic deposits comprising 30 nodal nevi and 15 melanoma metastases. The latter were not straightforward from a diagnostic perspective because they coexisted with nodal nevi or were present in perinodal fibrous tissue. All nodal nevi were negative for PRAME and all melanoma metastases were diffusely positive for PRAME IHC. The authors also reported the novel use of a PRAME/melan-A dual-label immunostain. The results showed that PRAME IHC may be useful in assessing diagnostically challenging nodal melanocytic deposits, such as intraparenchymal nodal nevi, or metastases confined to the capsular fibrous tissue, as well as in the setting of small metastases coexisting with a nodal nevus in the same lymph node.

Lezcano C, Pulitzer M, Moy AP, et al. Immunohistochemistry for PRAME in the distinction of nodal nevi from metastatic melanoma. Am J Surg Pathol. 2020;44(4):503–508.

Correspondence: Dr. Cecilia Lezcano at lezcanom@mskcc.org

Diagnostic algorithm for diagnosis of intraepithelial fallopian tube lesions

Intraepithelial fallopian tube neoplasia is thought to be a precursor lesion to high-grade serous carcinoma of the Müllerian adnexae, particularly in women with BRCA1 or BRCA2 mutations. This association has led to recommendations to assess fallopian tubes for intraepithelial atypia. However, the diagnostic reproducibility of a diagnosis of intraepithelial neoplasia is unclear. The authors conducted a study in which two gynecologic pathologists independently evaluated sections of fallopian tubes from a sample of women (N = 198, 623 slides) undergoing salpingectomy. Fifty-four percent (101) of the women were undergoing risk-reducing salpingo-oophorectomy. The pathologists were blinded to patient histories and prior diagnoses. They rendered one of three diagnoses for each slide: negative for fallopian tube intraepithelial neoplasia (FTIN), indeterminate for FTIN, or definite for FTIN. Cases that were considered definite for FTIN or suspicious for FTIN based on histology were stained with p53 and Ki67. The pathologists agreed on the diagnosis of definite for FTIN 61.5 percent of the time. There was no agreement on the diagnosis of indeterminate for FTIN for any cases. Fifteen cases that were indeterminate for FTIN and 12 that were definite for FTIN were stained with p53 and Ki67. Two of the indeterminate cases had p53-positive foci. Five of the definite cases had p53-positive foci. In three of the remaining eight definite cases, there was obvious carcinoma present, but the carcinoma did not stain with p53, suggesting a possible null phenotype. The authors proposed that immunostains should only be used to aid in the diagnosis of FTIN in cases with indeterminate histology. The use of p53 IHC in cases that were considered definite for FTIN by histology was minimally helpful and often further confused the diagnosis.

Perrone ME, Reder NP, Agoff SN, et al. An alternate diagnostic algorithm for the diagnosis of intraepithelial fallopian tube lesions. Int J Gynecol Pathol. 2020;39(3):261–269.

Correspondence: Dr. Marie E. Perrone at perronem@uw.edu

Invasive stratified mucin-producing carcinoma of the cervix

Invasive stratified mucin-producing carcinoma (ISMC) is a recently described tumor with similar morphology to the stratified mucin-producing intraepithelial lesion. Stratified mucin-producing intraepithelial lesion and ISMC likely arise from human papillomavirus (HPV)-infected reserve cells in the cervical transformation zone that retain their pluripotential ability to differentiate into various architectural and cytologic patterns. This is important because small studies have suggested that ISMC may be a morphologic pattern associated with more aggressive behavior than the usual HPV-associated adenocarcinoma. The authors studied the morphologic spectrum of this entity and its associations with other, more conventional patterns of HPV-associated carcinomas. An international panel of gynecologic pathologists reviewed full slide sets from 52 cases of ISMC and classified them according to the new International Endocervical Criteria and Classification system. Tumors were categorized as ISMC if they demonstrated stromal invasion by solid nests of neoplastic cells with at least focal areas of mucin stratified throughout the entire thickness, as opposed to conventional tall columnar cells with luminal gland formation. The analysis included tumors comprising pure ISMC and those mixed with other morphologic patterns. Twenty-nine (56 percent) pure ISMCs and 23 (44 percent) ISMCs mixed with other components were identified. The other components included 13 cases of usual-type adenocarcinoma, six adenosquamous carcinoma, three mucinous-type adenocarcinoma, and one high-grade neuroendocrine carcinoma. ISMC displayed architectural diversity (insular, lumen forming, solid, papillary, trabecular, micropapillary, and single cells) and variable cytologic appearance (eosinophilic cytoplasm, cytoplasmic clearing, histiocytoid features, glassy cell-like features, signet ring-like features, bizarre nuclei, and squamoid differentiation). Awareness of the spectrum of morphologies in ISMC is important for accurate and reproducible diagnosis so that future studies can be conducted to determine the clinical significance of ISMC.

Stolnicu S, Segura S, Parra-Herran C, et al. Invasive stratified mucin-producing carcinoma (ISMC) of the cervix: A study on morphologic diversity. Am J Surg Pathol. 2020;44(7):873–880.

Correspondence: Dr. Kay J. Park at parkk@mskcc.org

Immune response and stromal changes in DCIS of the breast

Ductal carcinoma in situ-associated stromal changes and an influx of immune cells might be mediators of progression to invasive breast cancer. The authors studied the interaction between DCIS-associated stromal changes and immune cell distribution and composition in a well-characterized patient cohort. The retrospective study included 472 patients with DCIS. The presence of stromal changes, signs of regression, and DCIS-associated immune cell position were determined on H&E-stained slides. Immune cell composition was characterized by IHC (CD4, CD8, CD20, CD68, and FOXP3). The number of intraductal immune cells was quantified per mm². The authors explored the interaction between stromal changes, signs of DCIS regression, immune cell composition, and location. Stromal changes and signs of DCIS regression were identified in 30 percent and seven percent of the patients, respectively. Intraductal immune cells primarily comprised CD68+ macrophages and CD8+ T cells. Patients with stromal changes had a significantly lower influx of immune cells within the duct. DCIS regression was associated with an increased number of intraductal FOXP3+ T cells. The highest number of intraductal CD8+ T cells was seen in the ER+ HER2+ subtype. The authors suggested that DCIS-associated stromal changes prevent interaction between immune cells and DCIS cells. However, in cases of DCIS regression, they surmised that there is direct interaction between DCIS cells and immune cells, in particular FOXP3+ cells. Furthermore, the increased number of intraductal CD8+ T cells in the ER+ HER2+ DCIS subtype suggested a subtype-specific immune response, which is likely to play a role in the distinct biological behavior of different DCIS subtypes.

Agahozo MC, Westenend PJ, van Bockstal MR, et al. Immune response and stromal changes in ductal carcinoma in situ of the breast are subtype dependent. Mod Pathol. 2020. doi.org/10.1038/s41379-020-0553.9

Correspondence: Marie Colombe Agahozo at m.agahozo@erasmusmc.nl

Fibroepithelial lesions revisited: implications for diagnosis and patient management

Fibroepithelial lesions of the breast, comprising the fibroadenoma and phyllodes tumor, are a unique group of neoplasms that share histological characteristics but differ in their clinical behavior. The fibroadenoma is the most common benign breast tumor in women, while the phyllodes tumor is rare and may be associated with recurrence, grade progression, and even metastasis. The diagnosis of fibroadenoma is usually straightforward, with such recognized histological variants as the cellular, complex, juvenile, and myxoid forms. The phyllodes tumor comprises benign, borderline, and malignant varieties and is graded using a constellation of histological criteria, including degree of stromal hypercellularity, atypia, mitoses, stromal overgrowth, and nature of the tumor borders. While phyllodes tumor grade correlates with clinical behavior, interobserver variability in assessing multiple parameters that are potentially of different biological weighting leads to significant challenges in determining grade and, consequently, therapy. Differential diagnostic considerations along the spectrum of fibroepithelial tumors can be problematic in routine practice. Recent discoveries about the molecular underpinnings of these tumors may have diagnostic, prognostic, and therapeutic implications.

Tan PH. Fibroepithelial lesions revisited: implications for diagnosis and management. Mod Pathol. 2020. doi.org/10.1038/s41379-020-0583-3.