Gross Specimen Handling Procedures Do Not Impact the Occurrence of Spread Through Air Spaces (STAS) in Lung Cancer

ola Kala shared this article with you from Inoreader Gross Specimen Handling Procedures Do Not Impact the Occurrence of Spread Through Air Spaces (STAS) in Lung Cancer Μέσω The American Journal of Surgical Pathology - Current Issue Spread Through Air Spaces (STAS) is a form of invasion characterized by neoplastic cell dissemination in the lung parenchyma surrounding the outer edge of the tumor. Its possible artifactual origin is widely debated in the literature. The aim of this study is to investigate the potential impact of gross sampling procedures in causing STAS. A prospective series of 51 surgical lung specimens was collected (35 adenocarcinomas, 68.6%; 13 squamous cell carcinomas, 25.5%; 2 large-cell neuroendocrine carcinomas, 3.9%; 1 atypical carcinoid, 2%). The fresh tissue was sectioned with a new and clean blade for each cut, to obtain a tissue slice comprising the upper lung parenchyma, the tumor, and the lower parenchyma. This slice was cut in half and separately processed. The same procedure was repeated in the residual (specular) specimen after formalin fixation. STAS was identified in 33/51 (64.7%) cases, the predominant pattern being cluster formation (29 cases, 87.9%), the remaining 4 cases having single-cell invasion. Comparing STAS detection in upper and lower lung parenchyma areas (ie, before and after the blade crossed the tumor), no significant preferential STAS distribution was observed, indeed being almost overlapping (60.6% and 63.6% for fresh and 61.3% and 65.6% for fixed tissues, respectively). There was no difference between STAS occurrence in freshly cut and fixed corresponding samples. These findings indicate that STAS is not a pathologist-related artifactual event because of knife transportation of tumor cells during gross specimen handling and support the notion that it is a phenomenon preexisting to surgical tissue processing. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Expanding the Spectrum of Microscopic and Cytogenetic Findings Associated With Spitz Tumors With 11p Gains

ola Kala shared this article with you from Inoreader Expanding the Spectrum of Microscopic and Cytogenetic Findings Associated With Spitz Tumors With 11p Gains Μέσω The American Journal of Surgical Pathology - Current Issue A subset of Spitz tumors is associated with a copy number increase of chromosome 11p and activating mutations of HRAS. These aberrations have been reported to occur in association with desmoplastic Spitz nevi. Little is known to what extent 11p gains can also be found in nondesmoplastic tumors. To learn more about the spectrum of microscopic and cytogenetic changes that can be seen in Spitz lesions in association with 11p gains, we reviewed the clinical and pathologic features of 40 cases. Patient ages ranged from 3 to 75 years. The most common anatomic site was the head and neck region, followed by the upper extremities. Prominent d esmoplasia was present in 10 cases. Seven tumors lacked significant stromal fibrosis. Twenty tumors were mitotically active. Novel microscopic features encountered in a few cases include a tumor with a polypoid silhouette and papillomatous surface and rare atypical tumors with a deep bulbous growth pattern. Among 36 cases analyzed by single-nucleotide polymorphism array or comparative genomic hybridization, 28 tumors had gains of the entire or near-entire p-arm of chromosome 11 with no other coexisting unbalanced genomic aberration. Eight cases had additional changes; 6 of these with 1 additional aberration per case, and 2 cases had several chromosomal aberrations. We also examined a subset of tumors by fluorescence in situ hybridization for the HRAS gene locus (11p15.5). All tumors were fluorescence in situ hybridization–positive. In conclusion, we expand the spectrum of pathologic findings associated with Spitz tumors with 11p gains. This cytogenetic aberration is not restricted to desmoplastic Spitz nevi. It can also be seen in nondesmoplastic and papillomatous lesions and atypical melanocytic tumors with a deep bulbous growth. We also document that in some Spitz tumors additional cytogenetic aberrations may be found, the significance of which remains to be determined. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinicopathologic Features of Varicella Zoster Virus Infection of the Upper Gastrointestinal Tract

ola Kala shared this article with you from Inoreader Clinicopathologic Features of Varicella Zoster Virus Infection of the Upper Gastrointestinal Tract Μέσω The American Journal of Surgical Pathology - Current Issue Reactivation of latent varicella zoster virus (VZV) may be limited to a dermatome or involve multiple organs, including the gastrointestinal tract. Although gastrointestinal manifestations of disseminated zoster have been likened to those of herpes simplex virus (HSV), histologic features of VZV-related injury to the tubular gut are not well-documented. We performed this study to describe the clinicopathologic features of VZV-related gastrointestinal injury. We identified 6 such patients with VZV infection. All involved the upper gastrointestinal tract, affecting the esophagus (n=3), stomach (n=2), or both (n=1). All patients wer e immunocompromised adults with hematologic malignancies (n=5) or a heart transplant (n=1); 3 with hematologic malignancies had received stem cell transplants. Five patients had cutaneous and gastrointestinal zoster; 1 had gastrointestinal disease alone. When compared with 14 HSV-related esophagitis controls, there were several notable differences. VZV caused hemorrhagic ulcers with nodularity or erythema, whereas HSV produced round, shallow ulcers on a background of nearly normal mucosa (P=0.01). VZV-related ulcers featured fibrin-rich, pauci-inflammatory exudates compared with the macrophage-rich exudates of HSV (P=0.003). The cytopathic changes of VZV were present at all levels of the squamous epithelium, especially in a peripapillary distribution. In contrast, HSV inclusions were located in the superficial layers (P=0.003) and detached keratinocytes. Unlike HSV, VZV involved the stomach, producing hemorrhage accompanied by striking apoptosis in the deep glands. We conclude that VZV produces unique patterns of gastrointestinal injury that facilitate its diagnosis. Recognition of gastrointestinal VZV infection is important because it heralds potentially life-threatening disseminated disease. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Pseudocarcinomatous Squamous Hyperplasia Involving Bone: A Diagnostic Pitfall Mimicking Squamous Cell Carcinoma

ola Kala shared this article with you from Inoreader Pseudocarcinomatous Squamous Hyperplasia Involving Bone: A Diagnostic Pitfall Mimicking Squamous Cell Carcinoma Μέσω The American Journal of Surgical Pathology - Current Issue Background: Pseudocarcinomatous squamous hyperplasia (PSH) within the bone is uncommon and closely mimics well-differentiated squamous cell carcinoma (SCC). It arises from cutaneous or mucosal surfaces and grows directly into the bone. This study analyzes a large series of PSH and discusses the clinicopathologic features that facilitate its distinction from SCC. Design: Cases were identified from the surgical pathology files between 1985 and 2020. Results: The 31 cases included 21 males, 9 females, 1 unknown sex; who were 20 to 87 years old (average: 59 y). Sites included mandible—17, maxilla—5, toes—4, and 1 case from finger, femur, tibia, ischium, and unknown. Fourteen patients had a history of SCC, 13 treated with resection and chemoradiation and developed infected osteoradionecrosis, 4—medication-related osteonecrosis, 3—peripheral vascular disease, and diabetes mellitus, 3—trauma, 3—osteomyelitis, 3—unknown, and 1—hematologic malignancy. All cases exhibited severe osteomyelitis and nests of reactive keratinizing squamous epithelium that matured towards the bone surface, lacked significant atypia, or mitotic activity but permeated the medullary cavity. Patients with previous SCC developed PSH after 2 months to 8 years (average: 4 y). Nineteen of 30 patients had follow-up (2 to 48 mo, average: 17 mo); 6 patients experienced repeated debridements over 2 months to 1 year; no patient developed SCC. Conclusions: PSH involving bone is infrequent, complicates severe osteomyelitis, and is often therapy related. The clinical findings are usually not concerning for malignancy, however, the histologic findings are an important diagnostic pitfall because they mimic SCC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Amyloid-like Fibronectin Deposits in the Liver: A Novel Morphologic Finding

ola Kala shared this article with you from Inoreader Amyloid-like Fibronectin Deposits in the Liver: A Novel Morphologic Finding Μέσω The American Journal of Surgical Pathology - Current Issue Amyloid deposits in the liver are recognized by their hematoxylin and eosin (H&E) findings, consisting of acellular eosinophilic deposits in various compartments of the liver parenchyma, including the stroma, vessels, and rarely the hepatocytes. H&E findings that suggest amyloid are then confirmed by Congo red stains and subtyped when clinically needed. Two cases are reported with sinusoidal deposits of acellular material that closely mimicked amyloid on H&E, but were Congo red negative. Mass spectrometry–based proteomic analysis identified the material as fibronectin. In 1 case, the deposits were located in the sinusoids of a well-differentiated hepatocellular carcinoma and in 1 case in the sinusoids of a benign liver. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Dedifferentiated and Undifferentiated Melanomas

ola Kala shared this article with you from Inoreader Dedifferentiated and Undifferentiated Melanomas: Report of 35 New Cases With Literature Review and Proposal of Diagnostic Criteria Μέσω The American Journal of Surgical Pathology - Current Issue Dedifferentiated melanoma (DM) and undifferentiated melanoma (UM) is defined as a primary or metastatic melanoma showing transition between conventional and undifferentiated components (DM) or lacking histologic and immunophenotypic features of melanoma altogether (UM). The latter is impossible to verify as melanoma by conventional diagnostic tools alone. We herein describe our experience with 35 unpublished cases to expand on their morphologic, phenotypic, and genotypic spectrum, along with a review of 50 previously reported cases (total: 85) to establish the diagnostic criteria. By definition, the dedifferentiated/undifferen tiated component lacked expression of 5 routinely used melanoma markers (S100, SOX10, Melan-A, HMB45, Pan-melanoma). Initial diagnoses (known in 66 cases) were undifferentiated/unclassified pleomorphic sarcoma (n=30), unclassified epithelioid malignancy (n=7), pleomorphic rhabdomyosarcoma (n=5), other specific sarcoma types (n=6), poorly differentiated carcinoma (n=2), collision tumor (n=2), atypical fibroxanthoma (n=2), and reactive osteochondromatous lesion (n=1). In only 11 cases (16.6%) was a diagnosis of melanoma considered. Three main categories were identified: The largest group (n=56) comprised patients with a history of verified previous melanoma who presented with metastatic DM or UM. Axillary or inguinal lymph nodes, soft tissue, bone, and lung were mainly affected. A melanoma-compatible mutation was detected in 35 of 48 (73%) evaluable cases: BRAF (n=20; 40.8%), and NRAS (n=15; 30.6%). The second group (n=15) had clinicopathologic features similar to group 1, but a melan oma history was lacking. Axillary lymph nodes (n=6) was the major site in this group followed by the lung, soft tissue, and multiple site involvement. For this group, NRAS mutation was much more frequent (n=9; 60%) than BRAF (n=3; 20%) and NF1 (n=1; 6.6%). The third category (n=14) comprised primary DM (12) or UM (2). A melanoma-compatible mutation was detected in only 7 cases: BRAF (n=2), NF1 (n=2), NRAS (n=2), and KIT exon 11 (n=1). This extended follow-up study highlights the high phenotypic plasticity of DM/UM and indicates significant underrecognition of this aggressive disease among general surgical pathologists. The major clues to the diagnosis of DM and UM are: (1) presence of minimal differentiated clone in DM, (2) earlier history of melanoma, (3) undifferentiated histology that does not fit any defined entity, (4) locations at sites that are unusual for undifferentiated/unclassified pleomorphic sarcoma (axilla, inguinal, neck, digestive system, etc.), (5) unusual multifoca l disease typical of melanoma spread, (6) detection of a melanoma-compatible gene mutation, and (7) absence of another genuine primary (eg, anaplastic carcinoma) in other organs. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Correlation Between Immunohistochemistry and Sequencing in H3G34-Mutant Gliomas

ola Kala shared this article with you from Inoreader Correlation Between Immunohistochemistry and Sequencing in H3G34-Mutant Gliomas Μέσω The American Journal of Surgical Pathology - Current Issue Recurrent glycine-to-arginine/valine alterations at codon 34 (G34R/V) within H3F3A gene characterize a subset of hemispheric high-grade gliomas (HGG) affecting children and young adults. These tumors, defined as G34R/V-mutant gliomas, are histologically heterogenous, with microscopic features of either HGG or embryonal tumors (primitve neuroectodermal tumor-like features). To assess the value of immunohistochemistry (IHC) to detect G34R/V-mutated cases, we tested anti-histone G34V (clone 329E5) and anti-histone G34R (clone RM240) antibodies in a series of 28 formalin-fixed and paraffin-embedded samples. A total of 28 cases of hemis pheric, IDH-wt HGG mainly affecting children and young adults were evaluated by IHC and by sequencing. The median age of patients at diagnosis was 17 years (0.1 to 26 y). By IHC, 10 of the 28 cases showed nuclear positivity for G34R and 3 of the 28 cases for G34V. Molecular analysis of G34R/V-mutation status was successful in 24 of the 28 cases. Mutation at glycine 34 of the H3F3A gene was identified in 9 of the 24 tumors (37%) by direct sequencing, revealing 7 of 9 positive case by sequencing and 2 of 9 false negative cases by IHC. Two of 15 negative case by sequencing demonstrated a false positivity by IHC. In total, in 4 (16.6%) of 24 cases, IHC and mutational results were discordant: 2 tumors were negative by IHC (false negative) but harbored G34R mutation by sequencing, and 2 cases were positive by IHC (false positive by IHC) but wild type by sequencing. Moreover, most mutated cases showed loss of ATRX expression and/or p53 expression. The positivity by IHC with specific anti body tested is not highly predictive for presence of G34R/V mutation, but confirmation by sequencing is mandatory; G34R/V mutations should be suspected in all hemispheric tumor IDH1/2 wild type, showing loss of OLIG2 and ATRX and/or p53 expression. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

INSM1 Is Less Sensitive But More Specific Than Synaptophysin in Gynecologic High-grade Neuroendocrine Carcinomas: An Immunohistochemical Study of 75 Cases With Specificity Test and Literature Review

ola Kala shared this article with you from Inoreader INSM1 Is Less Sensitive But More Specific Than Synaptophysin in Gynecologic High-grade Neuroendocrine Carcinomas: An Immunohistochemical Study of 75 Cases With Specificity Test and Literature Review Μέσω The American Journal of Surgical Pathology - Current Issue Insulinoma-associated protein 1 (INSM1) has emerged as a promising diagnostic marker for high-grade neuroendocrine carcinomas (HGNECs); however, it is controversial whether INSM1 is more sensitive than conventional markers chromogranin, synaptophysin, and CD56. Here, we investigated immunohistochemical expression of INSM1 in 75 gynecologic HGNECs using full tissue sections (30 small-cell carcinomas [SmCCs], 34 large-cell neuroendocrine carcinomas [LCNECs], and 11 mixed SmCC and LCNEC), with specificity analysis in 422 gynecologic non-neuroendocrine tumors (410 in tissue microarrays and 12 full sections) and comparison with conven tional neuroendocrine markers for their sensitivity and specificity. Positive INSM1 staining was seen in 69 (92%) HGNECs, whereas chromogranin, synaptophysin, and CD56 staining was seen in 61 (81%), 72 (96%), and 44 (69%) tumors, respectively (INSM1 vs. chromogranin, P=0.09; INSM1 vs. synaptophysin, P=0.4942; and INSM1 vs. CD56, P View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Two Cases With Features of Lymphocyte Variant Hypereosinophilic Syndrome With STAT3 SH2 Domain Mutations

ola Kala shared this article with you from Inoreader Two Cases With Features of Lymphocyte Variant Hypereosinophilic Syndrome With STAT3 SH2 Domain Mutations Μέσω The American Journal of Surgical Pathology - Current Issue Lymphocyte variant hypereosinophilic syndrome (LV-HES) is a rare cause of eosinophilia that is due to eosinophilipoietic cytokine production by an immunophenotypically abnormal T-cell clone. The molecular pathogenesis of this disorder is largely unknown and only 1 case of LV-HES with a pathogenic STAT3 mutation has been described thus far. Here we report 2 cases of LV-HES with STAT3 SH2 domain mutations. These cases further support the model that activation of STAT3 signaling through STAT3 SH2 domain mutations is a recurrent event in LV-HES. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Malignant Diffuse Mesothelioma in Women: A Study of 354 Cases

ola Kala shared this article with you from Inoreader Malignant Diffuse Mesothelioma in Women: A Study of 354 Cases Μέσω The American Journal of Surgical Pathology - Current Issue No abstract available View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Male–Female Fertility Differentials

ola Kala shared this article with you from Inoreader Male–Female Fertility Differentials Across 17 High-Income Countries: Insights From A New Data Resource Μέσω Latest Results for European Journal of Population Abstract Obtaining cross-country comparative perspectives on male fertility has long been difficult, as male fertility is usually less well registered than female fertility. Recent methodological advancements in imputing missing paternal ages at childbirth enable us to provide a new database on male fertility. This new resource covers more than 330 million live births and is based on a consistent and well-tested set of methods. These methods allow us to handle missing information on the paternal age, which is missing for roughly 10% of births. The data resource is made available in the Human Fertility Collection and allows for the first time a comparative perspective on male fertility in high-income countries using high-quality birth register data. We analyze trends in male–female fertility quantum and tempo differentials across 17 high-income countries, dating as back as far as the late 1960s for some countries, and with data available for the majority of countries fro m the 1980s onward. Using descriptive and counterfactual analysis methods, we find substantial variation both across countries and over time. Related to the quantum we demonstrate that disparities between male and female period fertility rates are driven to a large degree by the interplay of parental age and cohort size differences. For parental age differences at childbirth, we observe a development toward smaller disparities, except in Eastern Europe. This observation fits with expectations based on gender theories. However, variation across countries also seems to be driven by factors other than gender equality. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.