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Virchows Archiv : An International... Jan 2022Apocrine change is recognised in benign, atypical and malignant lesions of the breast. Apocrine metaplasia, a frequent finding in the breast of women over the age of... (Review)
Review
Apocrine change is recognised in benign, atypical and malignant lesions of the breast. Apocrine metaplasia, a frequent finding in the breast of women over the age of 25 years, is most commonly seen in benign cysts with a simple or papillary configuration. Apocrine change is also recognised in other benign lesions including sclerosing adenosis, now known as apocrine adenosis. Apocrine atypia usually refers to cytological atypia in which there is at least threefold variation in nuclear size but architectural atypia may also occur. The distinction between atypical apocrine hyperplasia and non-high-grade apocrine ductal carcinoma in situ may be difficult due to the relative rarity of these entities and the lack of validated diagnostic criteria. Lobular carcinoma in situ (LCIS) with apocrine change is considered to be a variant of pleomorphic LCIS. An apocrine variant of encapsulated papillary carcinoma is also recognised. Apocrine change is described in invasive carcinoma, including no special type, lobular, micropapillary and mucinous variants. The recent WHO 2019 update recognises 'carcinoma with apocrine differentiation' as a special type breast carcinoma based on the presence of apocrine morphology in at least 90% of the tumour. Tumours with apocrine morphology are usually but not always hormone receptor negative. Human epidermal growth factor receptor 2 (HER-2) status is variable. Molecular studies have identified breast tumours with apocrine features and high expression of androgen receptor mRNA including 'luminal androgen receptor tumours' and 'molecular apocrine tumours'. The term 'pure apocrine carcinoma' has been proposed to describe an invasive carcinoma with apocrine morphology that is oestrogen and progesterone receptor negative and androgen receptor positive. HER-2 status may be positive or negative. This article reviews the pathology of benign, atypical and malignant apocrine lesions of the breast, with emphasis on diagnostic criteria including an approach to evaluation of apocrine lesions on needle core biopsy, and recent advances in our understanding of invasive apocrine carcinoma.
Topics: Adult; Biopsy, Large-Core Needle; Breast; Breast Neoplasms; Female; Fibrocystic Breast Disease; Humans; Sweat Gland Neoplasms
PubMed: 34537861
DOI: 10.1007/s00428-021-03185-4 -
Dermatologic Clinics Oct 2016Melanomas are a wide range of tumors that differ in their epidemiology, morphology, genetic profile, and biological behavior. They can be grouped as superficial... (Review)
Review
Melanomas are a wide range of tumors that differ in their epidemiology, morphology, genetic profile, and biological behavior. They can be grouped as superficial spreading melanoma, lentigo maligna, and nodular melanoma. Reflectance confocal microscopy is useful for the evaluation of skin lesions that are dermoscopically doubtful by increasing diagnostic accuracy and specificity. This article provides a comprehensive overview of the different confocal main morphologies of distinct melanoma types as a function of the anatomic location of the tumor.
Topics: Humans; Hutchinson's Melanotic Freckle; Intravital Microscopy; Melanocytes; Melanoma; Microscopy, Confocal; Mucous Membrane; Sensitivity and Specificity; Skin Neoplasms
PubMed: 27692447
DOI: 10.1016/j.det.2016.05.004 -
The American Journal of Surgical... Oct 2018Uterine perivascular epithelioid cell tumors (PEComas) are rare neoplasms that may show overlapping morphology and immunohistochemistry with uterine smooth muscle...
Uterine perivascular epithelioid cell tumors (PEComas) are rare neoplasms that may show overlapping morphology and immunohistochemistry with uterine smooth muscle tumors. In this study, we evaluated the morphologic, immunohistochemical, and molecular features of 32 PEComas, including 11 with aggressive behavior. Two distinct morphologies were observed: classic (n=30) and those with a lymphangioleiomyomatosis appearance (n=2). In the former, patients ranged from 32 to 77 (mean: 51) years and 13% had tuberous sclerosis. Tumors ranged from 0.2 to 17 (mean: 5.5) cm with 77% arising in the corpus. Epithelioid cells were present in 100% and a spindled component was seen in 37%. Nuclear atypia was low (53%), intermediate (17%), or high (30%). Mitoses ranged from 0 to 36 (mean: 6) and 0 to 133 (mean: 19) per 10 and 50 high-power fields, with atypical mitoses present in 30%. Thin and delicate vessels were noted in 100%, clear/eosinophilic and granular cytoplasm in 93%, stromal hyalinization in 73%, necrosis in 30%, and lymphovascular invasion in 10%. All tumors were positive for HMB-45, cathepsin K, and at least one muscle marker, with most expressing melan-A (77%) and/or MiTF (79%). A PSF-TFE3 fusion was identified in one while another showed a RAD51B-OPHN1 fusion. Follow-up ranged from 2 to 175 (mean: 41) months, with 63% of patients alive and well, 20% dead of disease, 13% alive with disease, and 3% dead from other causes. In the latter group (n=2), patients were 39 and 49 years old, one had tuberous sclerosis, while the other had pulmonary lymphangioleiomyomatosis. Both tumors expressed HMB-45, cathepsin K, and muscle markers, but lacked TFE3 and RAD51B rearrangements. The 2 patients are currently alive and well. Application of gynecologic-specific criteria (≥4 features required for malignancy: size ≥5 cm, high-grade atypia, mitoses >1/50 high-power fields, necrosis, and lymphovascular invasion) for predicting outcome misclassified 36% (4/11) of aggressive tumors; thus, a modified algorithm with a threshold of 3 of these features is recommended to classify a PEComa as malignant.
Topics: Adult; Aged; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Biomarkers, Tumor; DNA-Binding Proteins; Epithelioid Cells; Female; Gene Fusion; Genetic Predisposition to Disease; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Middle Aged; Mitosis; Perivascular Epithelioid Cell Neoplasms; Phenotype; Predictive Value of Tests; Reproducibility of Results; Tumor Burden; Uterine Neoplasms
PubMed: 30001237
DOI: 10.1097/PAS.0000000000001119 -
Modern Pathology : An Official Journal... Jun 2023Uterine inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms that frequently harbor ALK gene rearrangements and have a low risk of metastasis. We...
Uterine inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms that frequently harbor ALK gene rearrangements and have a low risk of metastasis. We reported 3 of these tumors mimicking the appearance of leiomyoma in their recurrence. These patients were 34, 43, and 45 years old. Two uterine tumors demonstrated classic morphology, with combined myxoid, compact fascicular, and hyalinized patterns and spindled cells with bipolar cytoplasmic processes, moderate atypia, and lymphoplasmacytic inflammatory infiltrates. The third had a "leiomyoma-like" appearance, with fascicles of plump spindled cells and a sparse lymphoplasmacytic infiltrate. ALK immunohistochemistry was positive in all the tumors, and all demonstrated ALK rearrangements using fluorescence in situ hybridization (n = 2) and/or RNA sequencing (n = 2). Two classic IMTs recurred at 3 and 50 months in the lung and abdomen, respectively, and recurrent tumors had a "leiomyoma-like" appearance, with 0 and 1 mitosis per 10 high-power fields, no inflammation in 1, and a sparse lymphocytic infiltrate in the other. ALK was positive in both tumors; 1 with available tissue showed an IGFBP5::ALK fusion using RNA sequencing. The third patient, who had a "leiomyoma-like" uterine tumor, experienced multiple recurrences, first in the abdomen at 100 months showing a similar appearance. Subsequent recurrence at 105 months showed transmural invasion of the sigmoid colon and a similar microscopic appearance but with the addition of infiltrative borders, moderate cellularity, mild-to-moderate atypia, and 10 mitoses per 10 high-power fields. Both recurrences were positive for ALK, and RNA sequencing revealed the same ACTG2::ALK fusion transcript identified in the primary tumor. The patient was treated with crizotinib, resulting in prolonged clinical remission, with no evidence of disease at 168 months from the initial surgery. Although "leiomyoma-like" uterine IMTs have been recently described, to our knowledge, this is the first report of recurrence of these tumors and the first report of a "leiomyoma-like" appearance in the recurrences of conventional uterine IMTs. A low threshold for performing ALK immunohistochemistry on recurrent uterine tumors can identify patients who may benefit from tyrosine kinase inhibitors.
Topics: Female; Humans; Anaplastic Lymphoma Kinase; In Situ Hybridization, Fluorescence; Neoplasm Recurrence, Local; Leiomyoma; Uterine Neoplasms; Biomarkers, Tumor
PubMed: 36806735
DOI: 10.1016/j.modpat.2023.100143 -
Methods in Molecular Biology (Clifton,... 2019Intraductal papillary mucinous neoplasms (IPMNs) characteristically consist of mucin-filled dilated ducts lined with neoplastic cells forming papillae with a diverse...
Intraductal papillary mucinous neoplasms (IPMNs) characteristically consist of mucin-filled dilated ducts lined with neoplastic cells forming papillae with a diverse range of morphologies and varying grades of atypia. Based on morphological characteristics and immunohistochemical reaction against mucin proteins, IPMNs are classified into four distinct subtypes: gastric, intestinal, pancreatobiliary, and oncocytic. In this chapter, histomorphological criteria and techniques of immunohistochemical staining and its evaluation for subtyping IPMNs are described.
Topics: Biomarkers, Tumor; Biopsy; Humans; Immunohistochemistry; Mucins; Pancreatic Intraductal Neoplasms
PubMed: 30378039
DOI: 10.1007/978-1-4939-8879-2_1 -
British Journal of Haematology Feb 2023Numerous studies have shown peculiar morphological anomalies in COVID-19 patients' smears. We searched all the peer-reviewed scientific publications that explicitly... (Review)
Review
Numerous studies have shown peculiar morphological anomalies in COVID-19 patients' smears. We searched all the peer-reviewed scientific publications that explicitly reference the cytomorphological alterations on peripheral blood smears of patients with COVID-19. We extracted data from sixty-five publications (case reports, patient group studies, reviews, and erythrocyte morphology studies). The results show that frequent alterations concern the morphology of lymphocytes (large lymphocytes with weakly basophilic cytoplasm, plasmacytoid lymphocytes, large granular lymphocytes). Neutrophils display abnormal nuclei and cytoplasm in a distinctive cytomorphological picture. Besides a left shift in maturation, granulations can be increased (toxic type) or decreased with areas of basophilia. Nuclei are often hyposegmented (pseudo-Pelger-Huёt anomaly). Apoptotic or pycnotic cells are not uncommon. Monocytes typically have a large cytoplasm loaded with heterogeneous and coalescing vacuoles. Platelets show large and giant shapes. The presence of erythrocyte fragments and schistocytes is especially evident in the forms of COVID-19 that are associated with thrombotic microangiopathies. Such atypia of blood cells reflects the generalized activation in severe COVID-19, which has been demonstrated with immunophenotypic, molecular, genetic, and functional methods. Neutrophils, in particular, are involved in the pathophysiology of hyperinflammation with cytokine storm, which characterizes the most unfavorable evolution.
Topics: Humans; COVID-19; Pelger-Huet Anomaly; Neutrophils; Monocytes; Killer Cells, Natural
PubMed: 36203344
DOI: 10.1111/bjh.18489 -
Histopathology Jan 2019The classification of neoplastic precursor lesions in the urinary tract has evolved slowly with the gradual accumulation of clinicopathological data. Current... (Review)
Review
The classification of neoplastic precursor lesions in the urinary tract has evolved slowly with the gradual accumulation of clinicopathological data. Current nomenclature was codified most recently by the 2016 WHO classification, which is based on primary data with clinical outcome, consensus group statements and considerations of practical utility in routine diagnosis. This review discusses precursor lesions of urothelial, squamous and glandular lineage. For urothelial neoplasia, both flat lesions with atypia and early 'difficult-to-classify' proliferations are considered. Subtypes of squamous metaplasia, florid non-invasive squamous proliferations and frank squamous dysplasia are also addressed. Finally, rare glandular precursors of adenocarcinoma are reviewed, to include intestinal metaplasia, glandular dysplasia and villous adenoma. For each category, morphology (including differential diagnostic considerations), immunohistochemistry and any known molecular correlates are detailed. The goal is to provide a concise, practical up-to-date overview of this complex topic.
Topics: Adenocarcinoma; Adenoma; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Humans; Precancerous Conditions; Urinary Bladder Neoplasms; Urothelium
PubMed: 30565304
DOI: 10.1111/his.13762 -
Annales de Dermatologie Et de... Jan 2017Nested melanoma in elderly subjects is an entity that has been reported in the literature only since 2012. In this paper, we describe its distinctive clinical,...
BACKGROUND
Nested melanoma in elderly subjects is an entity that has been reported in the literature only since 2012. In this paper, we describe its distinctive clinical, dermatoscopic and histopathological features and compare them to previous published cases, with the aim of highlighting certain specific criteria of this melanoma subtype.
CASE REPORT
A 52-year-old man was referred for the presence on his chest of a large suspicious pigmented lesion of irregular shape and colour. Dermatoscopically, the lesion was chaotic and characterized by a black, structureless, eccentric area with some peripheral globules as well as some segmental radial lines. Histopathological examination revealed the presence of an asymmetric lesion with large junctional melanocytic nests showing a focal tendency to gathering and some cytological atypia. A diagnosis of nested melanoma was ultimately made.
DISCUSSION
Nested melanoma of the elderly represents a distinct anatomoclinical variant of superficial spreading melanoma. Clinically, the lesion is usually large and occurs in photodamaged skin. We would stress that the "elderly" criterion is not mandatory given the numerous cases reported in people under 60 years. The main dermatoscopic feature is a globular pattern, but several features characteristic of superficial spreading melanoma may also be present. Histological diagnosis may be difficult because of the mainly nested pattern, and the condition may be confused histologically with a benign junctional nevus. But these large junctional nests of different sizes, with bridging and cytonuclear atypias, together with asymmetry of the lesions are the hallmark of this special kind of melanoma.
Topics: Dermoscopy; Diagnosis, Differential; Humans; Male; Melanocytes; Melanoma; Middle Aged; Skin Neoplasms; Thorax
PubMed: 27771125
DOI: 10.1016/j.annder.2016.09.036 -
Cancers Jan 2023In cytologic analysis of lung nodules, specimens classified as atypia cannot be definitively diagnosed as benign or malignant. Atypia patients are typically subject to...
In cytologic analysis of lung nodules, specimens classified as atypia cannot be definitively diagnosed as benign or malignant. Atypia patients are typically subject to additional procedures to obtain repeat samples, thus delaying diagnosis. We evaluate morphologic categories predictive of lung cancer in atypia patients. This retrospective study stratified patients evaluated for primary lung nodules based on cytologic diagnoses. Atypia patients were further stratified based on the most severe verbiage used to describe the atypical cytology. Logistic regressions and receiver operator characteristic curves were performed. Of 129 patients with cytologic atypia, 62.8% later had cytologically or histologically confirmed lung cancer and 37.2% had benign respiratory processes. Atypia severity significantly predicted final diagnosis even while controlling for pack years and modified Herder score (p = 0.012). Pack years, atypia severity, and modified Herder score predicted final diagnosis independently and while adjusting for covariates (all p < 0.001). This model generated a significantly improved area under the curve compared to pack years, atypia severity, and modified Herder score (all p < 0.001) alone. Patients with severe atypia may benefit from repeat sampling for cytologic confirmation within one month due to high likelihood of malignancy, while those with milder atypia may be followed clinically.
PubMed: 36672346
DOI: 10.3390/cancers15020397 -
The American Journal of Surgical... Sep 2023Hepatic angiosarcomas are aggressive malignant tumors of the liver with variable morphology. One of the rare morphologies is that of the sinusoidal growth pattern, which...
Hepatic angiosarcomas are aggressive malignant tumors of the liver with variable morphology. One of the rare morphologies is that of the sinusoidal growth pattern, which is challenging to diagnose because of its subtle imaging and morphologic findings. This retrospective study characterizes the clinical, histologic, and immunohistochemical features of sinusoidal hepatic angiosarcomas. Thirteen cases were included in the study, comprising 12 (92.3%) needle core biopsies and 1 wedge biopsy; one of the needle biopsies also had a subsequent resection specimen available for review. Multiple biopsies were needed to make the diagnosis in 4 cases. At least moderate sinusoidal dilatation was seen in 53.8% of cases. Increased cellularity within the sinusoids was seen at both low-power and high-power magnification (69.2% and 84.6%, respectively). Cytologic atypia ranged from mild to marked. Multinucleated tumor cells were present in most cases (10/13 cases) but were often sparse. Mitotic activity was identified in 5/13 cases. ERG immunostains were more reliable than CD31 and CD34 in identifying the tumor cells. Ki-67 proliferative index ranged from 5% to 30%. p53 immunostains were available in 9 cases and c-MYC in 7 cases; they were positive in 62.5% and 33.3% of cases, respectively and had a mutually exclusive staining pattern. In summary, this rare pattern of hepatic angiosarcoma is challenging to diagnose but has distinctive morphologic findings that can be supplemented with immunostains to establish the diagnosis.
Topics: Humans; Hemangiosarcoma; Retrospective Studies; Liver Neoplasms; Biopsy; Biopsy, Large-Core Needle
PubMed: 37357916
DOI: 10.1097/PAS.0000000000002082