Human Pathology

Thirteen years ago, we pointed out that ovarian transitional cell carcinomas (TCCs) and conventional high-grade serous carcinomas (HGSC) had similar genetic alterations and clinical behavior. Consequently, ovarian TCC is now classified as a morphologic variant of HGSC. Defective homologous recombination, resulting from genetic or epigenetic inactivation of DNA damage repair genes, such as BRCA1/2, occurs in approximately 50% of the HGSCs. Although BRCA mutations have been associated with HGSCs with SET features, little is known about the role of non-BRCA homologous recombination repair (HRR) genes and the HRR status in these tumors...

Rosai-Dorfman disease (RDD) is an uncommon histiocytic disorder typically involving lymph nodes and less frequently extranodal tissues. RDD involving the breast is rare and may clinically and radiologically mimic neoplastic and non-neoplastic disorders. We report seven patients with breast RDD, describe their clinicoradiologic and pathologic features, and discuss the differential diagnosis. Patients, ranging from 15 to 74 years of age, presented with unilateral and unifocal (5/7) or bilateral and multifocal (2/7) masses...

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) with concurrent BCL2 and IRF4 rearrangements are rare. It is unclear whether such cases should be classified as large B- cell lymphoma with IRF4 rearrangement or FL/DLBCL-not otherwise specified. We identified 5 adult patients (FL, N=3 and FL/DLBCL, N=2) with concurrent BCL2 and IRF4 rearrangements. The median age at presentation was 77 years, and three patients presented with advanced stage disease. Both nodal and extranodal sites were involved and involvement was not limited to head and neck region...

Tumor depth evaluation is essential for pathological tumor staging because it affects clinical management as an independent risk factor for lymph node metastasis in colorectal cancers. However, poor interobserver variability of invasion depth has been reported. This study aimed to clarify the effectiveness of desmin immunostaining in the histological diagnosis of colorectal cancer. Overall, 63 sets of slides of colorectal cancer stained with hematoxylin and eosin (H&E) and desmin were prepared and independently reviewed by four examiners...

BACKGROUND: Current management of patients with non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) is lobectomy with close clinical follow-up. Because this entity is still young, we present our 5-year institutional experience with NIFTP since that time. METHODS: Cases of NIFTP diagnosed from 2017-2022 were identified. Data points including patient demographics, radiology, cytologic and pathologic diagnoses, molecular profiles, and clinical follow-up were documented...

Marginal zone lymphoma (MZL) is a primary, indolent small B-cell lymphoma. Subtypes include nodal, splenic, and those of extranodal mucosa-associated lymphoid tissue (MALT). These are slow growing and generally exhibit low rates of transformation to diffuse large B-cell lymphoma (DLBCL). At initial diagnosis, there can be an increase in large cells that does not meet criteria for DLBCL. Prior studies have noted this finding but the clinical significance of these large cells has not been well established. 161 cases of marginal zone lymphoma from 1994-2021 were evaluated, including all subtypes...

Anaplastic large cell lymphoma (ALCL), one of the most common T-cell lymphomas, shows unifying pathological features but is clinically and genetically heterogeneous. One genetic subgroup, characterized by recurrent DUSP22 rearrangements (R), has distinct morphologic, immunophenotypic, and molecular features and can be identified in routine pathology practice using a breakapart (BAP) fluorescence in situ hybridization (FISH) probe. However, some cases show equivocal BAP-FISH findings (BAP-FISHEQ ) and the features of these cases are poorly understood...

A new molecular subtype classification method has been proposed for small cell lung carcinoma (SCLC). However, little is known about the differences between the pure (P-SCLC) and combined subtypes (C-SCLC). We aimed to compare the molecular subtype expression and genomic profiling in terms of clinical relevance between the two groups. 154 surgically resected SCLCs were analyzed for protein expression of four subtypes (ASCL1, NEUROD1, POU2F3, and YAP1) and two predictive markers (DLL3 and MYC) by immunohistochemistry (IHC)...

Rising healthcare costs have been linked to over-treatment and overuse of available resources. Identifying and eliminating low-value services is vital for reducing such costs. At many institutions, including ours, all ileostomy and colostomy specimens are sent for pathological evaluation. It is estimated that approximately 120,000 ileostomy/colostomy procedures are done every year, and at least 1 million patients have stomas at any given time in North America. Hence, we decided to analyze the pathological findings and cost-benefit of undertaking the pathological evaluation of these colostomy and ileostomy specimens...

IMPORTANCE & OBJECTIVES: The potential significance of tissue eosinophils melanomas is unknown. We strove to determine a potential association between the presence of tissue eosinophils and prognosis of patients with metastatic melanoma (MM). METHODS: A retrospective electronic data base was queried to identify patients (age > 18 years) evaluated January 1, 2011 - October 1, 2022 (inclusive) at our multi-site medical center, who had metastatic melanoma and at least 1 biopsy of melanoma or a melanocytic nevus that was reported to show eosinophils...

This special issue of Human Pathology, highlighting updates in dermatopathology, represents a carefully curated collection of articles written by authors invited for their respective areas of expertise. This issue covers a range of important topics in neoplastic, inflammatory, or special-site dermatopathology, with an emphasis on "high-stakes" or emerging diagnoses or those that would be otherwise encountered infrequently by most practicing pathologists. In addition, topics important in clinical practice, including considerations relating to skin of color and cognitive bias in dermatopathology, are addressed...

Graft-versus-host disease (GVHD) is one of the serious complications that may develop after hematopoietic cell transplantation (HCT), for hematologic malignancies, solid organ transplantation, and other hematologic disorders. GVHD develops due to T lymphocytes present in the graft attacking the host antigens which results in tissue damage. A significant number of HCT patients develop acute or chronic GVHD which may affect multiple organs including the liver. The diagnosis of hepatic GVHD (hGVHD) is challenging as many other conditions in HCT patients may lead to liver dysfunction...

Plasmablastic Lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin Lymphoma that shares features with Diffuse large B-cell Lymphoma (DLBCL). While significant progress has been made in treating DLBCL, the prognosis for PBL remains poor, highlighting the need to identify new therapeutic targets. Using RNA expression analysis, we compared the expression of genes involved in the Phosphatidylinositol-3-kinase (PI3K) and Mitogen-activated protein kinase (MAPK) signaling pathways between PBL and DLBCL. We employed critical PI3K (n=201) and MAPK (n=57) signaling probe sets to achieve this objective...

Double expressor lymphoma (DEL) is a subset of diffuse large B-cell lymphoma (DLBCL) characterized by the co-expression of MYC and BCL2 proteins with a poor prognosis. However, there are no standard criteria for evaluating the morphologic features of DEL. We aimed to analyze the prognostic value of the starry-sky pattern (SSP) and its correlation with clinicopathologic and genetic features in 153 DEL cases. The SSP was significantly associated with aggressive parameters, including c-MYC overexpression, CD5 expression, higher IPI, and age-adjusted IPI...

Stromal tumor infiltrating lymphocytes (sTIL) are a robust prognostic and predictive biomarker in triple negative breast carcinoma (TNBC). However, the sTIL compartment comprises different cell populations. The aim of the study is to characterize the distribution of T cells (CD3+ and CD8+), B cells and plasma cells, and explore their association with outcome in the surgical specimen of 62 patients. Furthermore, PD-L1 expression and the presence of tertiary lymphoid structures (TLS) are explored. Patients with higher sTIL achieve better progression free survival (PFS) (P=0...

Emerging infectious diseases are of great importance to public health and clinical practice. This review aims to characterize the clinical and histopathologic features of emerging infectious diseases with cutaneous manifestations in order to increase awareness of these entities among dermatologists, pathologists, and dermatopathologists.

HPV is detected in 30 to 50% of invasive penile carcinomas and it is frequently associated with basaloid and warty morphological features. Based on this heterogeneity and different clinical behavior, we hypothesized a variation in their HPV genotypic composition. To test this, we evaluated 177 HPV positive cases: basaloid (114), warty-basaloid (28) and warty (condylomatous) (35) invasive carcinomas. HPV DNA detection and genotyping was performed with PCR using SPF-10/DEIA/LiPA25 system. Nineteen HPV genotypes were detected...

BACKGROUND: A commercially available diagnostic gene expression profiling (GEP) assay [MyPathTM ] reportedly has high sensitivity and specificity in distinguishing nevi from melanoma based on manufacturer conducted studies. However, data regarding the performance of this GEP assay in routine clinical practice is lacking. OBJECTIVE: The purpose of this study was to better assess the real-world performance of GEP in a large academic practice. METHODS: Retrospective review of GEP scores were compared with final histomorphologic interpretation on a wide spectrum of melanocytic lesions demonstrating some degree of atypia...

Spindle cell lesions of the breast elicit a specific, relatively limited differential diagnosis, and accurate classification often requires careful morphologic evaluation and immunohistochemical workup. Low-grade fibromyxoid sarcoma (LGFMS) is a rare malignant fibroblastic tumor with deceptively bland spindle cell morphology. Involvement of the breast is exceedingly rare. We examined the clinicopathologic and molecular characteristics of three cases of breast/axillary LGFMS. In addition, we interrogated the immunohistochemical expression of MUC4, a commonly used marker of LGFMS, in other breast spindle cell lesions...

BACKGROUND: The gastrointestinal (GI) tract is a common site of amyloidosis, but the incidence, clinicopathologic features, and systemic implications of different types of GI amyloidosis are not well understood. METHODS: GI amyloid specimens (N = 2,511) typed using a proteomics-based method between 2008-2021 were identified. Clinical and morphologic features were reviewed in a subset of cases. RESULTS: Twelve amyloid types were identified, including AL (77...