Human Pathology

JAK2 rearrangement (JAK2-R) in acute lymphoblastic leukemia (ALL) is rare and often categorized as B-ALL with BCR::ABL1-like features based on the World Health Organization classification. We report 10 patients with JAK2-R ALL, 9 males and 1 female, with a median age 40.5 years. Eight patients presented with marked leukocytosis (median WBC, 63 × 10 9 /L) and hypercellular (>95%) bone marrow with increased lymphoblasts (72%-95%). There was no evidence of bone marrow fibrosis or hypereosinophilia. Immunophenotypic analysis showed 9 B-cell and 1 T-cell neoplasms...

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with several patient and disease associated variables known to impact prognosis. Tobacco smoking is an environmental factor associated with a greater incidence of AML, but there have been limited studies that evaluated smoking toward overall survival. We retrospectively searched for AML cases and collected clinical and diagnostic data for each case. We also used an independent next-generation sequencing (NGS) dataset to assess for a distinct mutational signature associated with smoking...

Histopathologic evaluation of the nail unit is an essential component in the diagnosis of nail unit disorders. This review highlights recent updates in nail unit histopathology and discusses literature covering a wide range of nail disorders including melanoma/melanocytic lesions, squamous cell carcinoma, onychomatricoma, onychopapilloma, onychomycosis, lichen planus, and other inflammatory conditions. Herein we also discuss recent literature on nail clipping histopathology, a useful and non-invasive diagnostic tool that continues to grow in popularity and importance to both dermatologists and dermatopathologists...

Cognitive bias refers to human thinking patterns, as well as pitfalls, that are reproducible. All pathologists are subject to cognitive bias. Importantly, cognitive bias is not intentionally discriminatory and is necessary to properly interpret the world around us, including microscopic slides. Thus, it is a useful exercise to examine cognitive bias in pathology, as exemplified in dermatopathology.

Intraluminal crystalloids are a common finding within malignant prostatic acini and are infrequently identified within benign glands. The proteomic composition of these crystalloids remains poorly understood and may provide insight regarding prostate cancer pathogenesis. Laser microdissection assisted liquid chromatography tandem mass spectrometry (LMD-LC-MS/MS) was performed to compare proteomic composition of corpora amylacea within benign acini (n=9), prostatic adenocarcinoma-associated crystalloids (n=8), benign (n=8), and malignant prostatic acini (n=6)...

A wide range of treatment options are available to patients with prostate cancer. Some treatments are standard (currently used) while some are emerging therapies. Androgen deprivation therapy is typically reserved for localized or metastatic prostate cancer not amenable to surgery. Radiation therapy may be offered to individuals for local therapy with curative intent in low- or intermediate-risk disease that may have a high probability of progression on active surveillance or where surgery is not suitable. Focal therapy/ablation treatment is an alternative approach for those who prefer to avoid radical prostatectomy for localized disease of low- or intermediate-risk or as salvage therapy after failed radiation therapy...

Testicular cancer is the most common solid neoplasm of adult men between the ages of 20 and 40 years. Germ cell tumors account for 95% of all testicular tumors. The assessment of staging is essential to guide further management of patients with testicular cancer and to prognosticate cancer-related outcomes. Postradical orchiectomy treatment options, including adjuvant therapy and active surveillance, vary based on the anatomical extent of disease, serum tumor markers, pathologic diagnosis, and imaging. This review provides an update on the germ cell tumor staging system adopted by the 8th edition of the American Joint Commission on Cancer (AJCC) Staging Manual, treatment implications, risk factors, and predictors of outcomes...

Merkel cell carcinoma (MCC) is an uncommon primary cutaneous neuroendocrine carcinoma associated with an adverse prognosis. In recent years, our understanding of MCC biology has markedly progressed. Since the discovery of the Merkel cell polyomavirus, it has become clear that MCC represents an ontogenetically dichotomous group of neoplasms with overlapping histopathology. Specifically, most MCCs arise secondary to viral oncogenesis, while a smaller subset is the direct result of UV-associated mutations. The distinction of these groups bears relevance in their immunohistochemical and molecular characterization, as well as in disease prognosis...

Neuroendocrine tumors of the prostate are rare and encompass a group of entities that are classified based on a combination of morphological and immunohistochemical features. Despite the 2016 World Health Organization classification of prostatic neuroendocrine tumors, variants have been reported that do not fit well in the categorization scheme. While the majority of these tumors arise in the setting of castration-resistant prostate cancer (postandrogen deprivation therapy), de novo cases may occur. In this review, we highlight the most significant pathological and immunohistochemical features, emerging biomarkers, and molecular features of such tumors...

Renal manifestations in patients with tuberous sclerosis complex (TSC) include cysts, angiomyolipoma, and renal cell carcinoma. Unlike many hereditary predisposition syndromes, the spectrum of renal tumors in TSC patients (including both angiomyolipoma and renal cell carcinoma) is broad, with significant morphologic heterogeneity. An improved understanding of histopathologic findings in TSC patients and associated clinicopathologic correlates has significant implications not just in establishing a diagnosis of TSC, but also in the recognition of sporadic tumors occurring secondary to somatic alterations of TSC1/TSC2/MTOR pathway genes and accurate prognostication...

The development of somatic-type malignancy (SM) in testicular germ cell tumor represents a major challenge in the diagnosis and treatment of testicular cancer. Most SMs are derived from teratoma, and the remainder is associated with yolk sac tumor. They occur more frequently in metastases than in primary testicular tumors. SMs demonstrate a variety of histologic types, including sarcoma, carcinoma, embryonic-type neuroectodermal tumor, nephroblastoma-like tumor, and hematologic malignancy. Sarcoma, particularly rhabdomyosarcoma, accounts for the majority of SMs in the primary testicular tumors, whereas carcinoma, particularly adenocarcinoma, is the most common SM in metastases...

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare autosomal dominant disease resulting from a frame-shift mutation in TREX1, an intracellular 3'-5' exonuclease 1. Hepatic findings include an elevated alkaline phosphatase (ALP) and nodular regenerative hyperplasia (NRH). Affected individuals typically succumb to brain lesions prior to clinically apparent hepatic manifestations; thus, little else is known about the hepatic pathology...

It has been suggested that most, if not all, extrarenal rhabdoid tumors of the vulva represent "proximal-type" epithelioid sarcomas. To better understand rhabdoid tumors of the vulva, we studied the clinicopathologic, immunohistochemical (IHC), and molecular features of 8 of these tumors and 13 extragenital epithelioid sarcomas. IHC analysis for cytokeratin AE1/AE3, EMA, S100, CD34, ERG, smooth muscle actin, desmin, and SMARCB1 (INI1) was performed. Ultrastructural study was done in one vulvar rhabdoid tumor...

No abstract text is available yet for this article.

Liver biopsy is essential for management in liver transplant patients with clinical features suspicious for acute cellular rejection (ACR). As more patients are transplanted for non-infectious indications, it has become increasingly common for them to receive treatment for presumed ACR before biopsy. The effect of pre-treatment on the classic histologic triad of ACR's mixed portal inflammation, endothelialitis, and bile duct damage is not well described. Here we report a retrospective study of 70 liver transplant biopsies performed on 53 patients for suspected ACR between 2018 and 2021...

This study examined PRAME expression by immunohistochemistry and reverse transcription quantitative PCR (RT-qPCR) in 202 histologically unequivocal conjunctival melanocytic lesions: 76 nevi, 29 benign melanoses, 25 low-grade conjunctival intraepithelial melanocytic lesions (LGCMIL), 26 high-grade conjunctival melanocytic intraepithelial lesions/in-situ melanoma (HGCMIL) and 46 invasive melanomas. PRAME score 0 was seen in 96% of nevi (73/76), 96% of benign melanoses (28/29) and 88% of LGCMIL (22/25). PRAME score 4 was seen in 50% HGCMIL (13/26) and 76% invasive melanomas (35/46)...

No abstract text is available yet for this article.

Ancillary tests are commonly used in the surgical pathology setting for diagnosing challenging neoplastic diseases of the liver and biliary tract, while histology and clinical correlation remain to be critically important. With continuous discoveries, more and more useful ancillary tests have become available, which can help distinguish between malignant and benign hepatocellular neoplasms, malignant and benign biliary tract entities, and intrahepatic and metastatic carcinomas. This review will focus on existing and emerging biomarkers (such as glutamine synthetase, organic anion transporting polypeptide 1B3, insulin-like growth factor-II mRNA binding protein-3, S100P, SMAD4, enhancer of zeste homolog 2, albumin, hepatocyte nuclear factor-1β, etc...

We studied pathogenic gene mutations and tumor mutation burden (TMB) in visible low grade dysplastic lesions in patients with inflammatory bowel disease (IBD). The dysplastic lesions with histologically normal mucosa in the background (group 1) were compared with dysplastic lesions occurring either in a background of chronic active colitis (group 2) or associated with synchronous carcinomas regardless of the status of the background mucosa (group 3). The TMB in group 3 was consistently higher in comparison to the group 1 and group 2 lesions, although the difference was not statistically significant...

BACKGROUND: WT1 immunostain is expressed in various benign and malignant neoplasms, as well as normal myoepithelial cells. WT1 shows differential expression in non-neoplastic, benign, and malignant neoplastic myoepithelial cells of the salivary gland. In this study, WT1 immunostain and other myoepithelial markers were compared to investigate the value of WT1 as a myoepithelial marker, and to delineate the expression profile of WT1 in non-salivary gland myoepithelial cells. METHODS: WT1, p63 and calponin immunostains were performed on normal and lesional tissues from the breast (adenosis, sclerosing adenosis, lactating adenoma, nipple adenoma, tubular adenoma, adenomyoepithelioma and adenoid cystic carcinoma (ACC)), skin (cutaneous mixed tumor, hidradenoma, spiradenoma and ACC), and salivary gland (pleomorphic adenoma and ACC)...