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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 -
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 -
The Lancet. Digital Health Feb 2023Endometrial cancer can be molecularly classified into POLE, mismatch repair deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP) subgroups.... (Randomized Controlled Trial)
Randomized Controlled Trial
Interpretable deep learning model to predict the molecular classification of endometrial cancer from haematoxylin and eosin-stained whole-slide images: a combined analysis of the PORTEC randomised trials and clinical cohorts.
BACKGROUND
Endometrial cancer can be molecularly classified into POLE, mismatch repair deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP) subgroups. We aimed to develop an interpretable deep learning pipeline for whole-slide-image-based prediction of the four molecular classes in endometrial cancer (im4MEC), to identify morpho-molecular correlates, and to refine prognostication.
METHODS
This combined analysis included diagnostic haematoxylin and eosin-stained slides and molecular and clinicopathological data from 2028 patients with intermediate-to-high-risk endometrial cancer from the PORTEC-1 (n=466), PORTEC-2 (n=375), and PORTEC-3 (n=393) randomised trials and the TransPORTEC pilot study (n=110), the Medisch Spectrum Twente cohort (n=242), a case series of patients with POLE endometrial cancer in the Leiden Endometrial Cancer Repository (n=47), and The Cancer Genome Atlas-Uterine Corpus Endometrial Carcinoma cohort (n=395). PORTEC-3 was held out as an independent test set and a four-fold cross validation was performed. Performance was measured with the macro and class-wise area under the receiver operating characteristic curve (AUROC). Whole-slide images were segmented into tiles of 360 μm resized to 224 × 224 pixels. im4MEC was trained to learn tile-level morphological features with self-supervised learning and to molecularly classify whole-slide images with an attention mechanism. The top 20 tiles with the highest attention scores were reviewed to identify morpho-molecular correlates. Predictions of a nuclear classification deep learning model serve to derive interpretable morphological features. We analysed 5-year recurrence-free survival and explored prognostic refinement by molecular class using the Kaplan-Meier method.
FINDINGS
im4MEC attained macro-average AUROCs of 0·874 (95% CI 0·856-0·893) on four-fold cross-validation and 0·876 on the independent test set. The class-wise AUROCs were 0·849 for POLE (n=51), 0·844 for MMRd (n=134), 0·883 for NSMP (n=120), and 0·928 for p53abn (n=88). POLE and MMRd tiles had a high density of lymphocytes, p53abn tiles had strong nuclear atypia, and the morphology of POLE and MMRd endometrial cancer overlapped. im4MEC highlighted a low tumour-to-stroma ratio as a potentially novel characteristic feature of the NSMP class. 5-year recurrence-free survival was significantly different between im4MEC predicted molecular classes in PORTEC-3 (log-rank p<0·0001). The ten patients with aggressive p53abn endometrial cancer that was predicted as MMRd showed inflammatory morphology and appeared to have a better prognosis than patients with correctly predicted p53abn endometrial cancer (p=0·30). The four patients with NSMP endometrial cancer that was predicted as p53abn showed higher nuclear atypia and appeared to have a worse prognosis than patients with correctly predicted NSMP (p=0·13). Patients with MMRd endometrial cancer predicted as POLE had an excellent prognosis, as do those with true POLE endometrial cancer.
INTERPRETATION
We present the first interpretable deep learning model, im4MEC, for haematoxylin and eosin-based prediction of molecular endometrial cancer classification. im4MEC robustly identified morpho-molecular correlates and could enable further prognostic refinement of patients with endometrial cancer.
FUNDING
The Hanarth Foundation, the Promedica Foundation, and the Swiss Federal Institutes of Technology.
Topics: Female; Humans; Eosine Yellowish-(YS); Hematoxylin; Deep Learning; Pilot Projects; Endometrial Neoplasms
PubMed: 36496303
DOI: 10.1016/S2589-7500(22)00210-2 -
Pathology Jan 2021The histopathological diagnosis of prostatic adenocarcinoma is challenged by the existence of numerous benign mimics. Most of these lesions have no clinical significance... (Review)
Review
The histopathological diagnosis of prostatic adenocarcinoma is challenged by the existence of numerous benign mimics. Most of these lesions have no clinical significance and many do not need to be reported. Their clinical relevance lies in the risk that they are misinterpreted as cancer. This review presents the histopathological features of benign mimics and discusses their distinction from cancer. The lesions that are most often misdiagnosed as cancer are atrophy and its variants, including simple atrophy, partial atrophy and post-atrophic hyperplasia. Benign proliferations are a group of lesions with crowded small glands with no or little nuclear atypia. The most problematic entity of this group is adenosis, which may have a more alarming architecture than some cancers. A diagnostic problem with atrophy and several of the benign proliferations is that the glands often have a discontinuous or absent basal cell layer. Hyperplastic and metaplastic lesions include basal cell hyperplasia. Basal cell hyperplasia may especially mimic prostate cancer with its small dark glands, variable nuclear atypia and a pseudoinfiltrative pattern, which may be present. The anatomical structure that most often causes diagnostic problems is the seminal vesicle. The mucosa of the seminal vesicle contains small acini, often with very pronounced nuclear atypia that may be misinterpreted as cancer. Pathologists need to be familiar with these mimics, as a false positive diagnosis of prostate cancer may lead to unnecessary radical treatment.
Topics: Adenocarcinoma; Atrophy; Diagnosis, Differential; Humans; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms
PubMed: 33070957
DOI: 10.1016/j.pathol.2020.08.006 -
CytoJournal 2022Cytology of the uterine cervix is one of the most widely utilized tests and is best known primarily for the cytologic changes seen in precancerous lesions and invasive... (Review)
Review
Cytology of the uterine cervix is one of the most widely utilized tests and is best known primarily for the cytologic changes seen in precancerous lesions and invasive cancer of the uterine cervix. The more common inflammatory conditions of cervicitis and vaginitis are close clinical differentials, especially when they give rise to excessive blood-stained vaginal discharge. These infective conditions also result in variation in the appearance of otherwise benign squamous and glandular cells in cervical cytology specimens. A variety of physiologic and pathologic conditions are responsible for the conversion of polymicrobial flora of the vagina to a monomicrobial one. The latter may overgrow the others and result in inflammation of the cervix and the vagina. Chronic irritation of the cervix due to intrauterine devices, chemical irritants, inflammation/infection, endocrine changes, and reparative changes can lead to worrisome parakeratosis, hyperkeratosis, and squamous metaplasia of non-keratinized squamous mucosa of the cervix and the vagina and may mimic HPV-related changes. Although some benign changes are specific for certain infections, for example, infestation, most of the reactive and hyperplastic cell morphology are important to recognize only due to the significant morphologic overlap with neoplastic changes in cytology specimens. Identification of different pathogens specifically may not be relevant from a clinical point of view, but is undoubtedly a cytologists' privilege to inform the clinician! This chapter describes in detail the cytoplasmic and nuclear reactive changes that are found in specific and non-specific inflammatory conditions. In addition, diagnostic pitfalls are emphasized where necessary.
PubMed: 35673696
DOI: 10.25259/CMAS_03_08_2021 -
Frontiers in Endocrinology 2021Oncocytes are cells that have abundant eosinophilic cytoplasm due to the accumulation of mitochondria; they are also known as oxyphils. In the thyroid they have been... (Review)
Review
Oncocytes are cells that have abundant eosinophilic cytoplasm due to the accumulation of mitochondria; they are also known as oxyphils. In the thyroid they have been called Hürthle cells but this is a misnomer, since Hürthle described C cells; for this reason, we propose the use of "oncocyte" as a scientific term rather than an incorrect eponym. Oncocytic change occurs in nontumorous thyroid disorders, in benign and malignant tumors of thyroid follicular cells, in tumors composed of thyroid C cells, and intrathyroidal parathyroid proliferations as well as in metastatic lesions. The morphology of primary oncocytic thyroid tumors is similar to that of their non-oncocytic counterparts but also is complicated by the cytologic features of these cells that include both abundant eosinophilic cytoplasm and large cherry red nucleoli. The molecular alterations in oncocytic thyroid tumors echo those of their non-oncocytic counterparts but in addition feature mitochondrial DNA mutations as well as chromosomal gains and losses. In this review we emphasize the importance of recognition of the spectrum of oncocytic thyroid pathology. The cell of origin, morphologic features including architecture, nuclear atypia and invasive growth, as well as high grade features such as mitoses and necrosis, enable accurate classification of these lesions. The molecular alterations underlying the pathological entity are associated with genetic alterations associated with oncocytic change. The arbitrary cut-off of 75% oncocytic change to classify a lesion as an oncocytic variant brings another complexity to the classification scheme of tumors that frequently have mixed oncocytic and non-oncocytic components. This controversial and often confusing area of thyroid pathology requires thoughtful and cautious investigation to clarify accurate diagnosis, prognosis and prediction for patients with oncocytic thyroid lesions.
Topics: Adenoma, Oxyphilic; Humans; Oxyphil Cells; Thyroid Gland; Thyroid Neoplasms
PubMed: 34012422
DOI: 10.3389/fendo.2021.678119 -
Seminars in Diagnostic Pathology May 2022Leiomyoma with nuclear atypia describes a group of uterine smooth muscle tumors with a wide range of histologic and clinical presentations and remarkable nuclear atypia.... (Review)
Review
Leiomyoma with nuclear atypia describes a group of uterine smooth muscle tumors with a wide range of histologic and clinical presentations and remarkable nuclear atypia. These include fumarate hydratase-deficient leiomyoma (FH-LM), intravenous leiomyomatosis (IV-LM), and leiomyoma with bizarre nuclei (LM-BN). Other uterine mesenchymal tumors, such as perivascular epithelioid tumor (PEComa) and inflammatory myofibroblastic tumors (IMFT) are the mimickers of leiomyoma with nuclear atypia. LM-BN is the primary tumor model with a long history in gynecologic pathology, but the histogenesis of LM-BN remains largely unknown. Differentiating LM-BN from other benign variants, tumors with uncertain malignant potential (STUMP), or fully malignant leiomyosarcoma (LMS) can be diagnostically challenging. Recent progress has improved the diagnosis of many types of leiomyoma with nuclear atypia based on their specific histology and molecular alterations. LM-BN is now a diagnosis of exclusion. In this article, I review the history of leiomyoma with nuclear atypia and compare the clinical, histologic, and molecular features of LM-BN with those of its mimics. In particular, I highlight the current progress made in molecular genetics and pitfalls in the diagnosis of different myogenic tumors with nuclear atypia.
Topics: Biomarkers, Tumor; Female; Humans; Leiomyoma; Leiomyosarcoma; Rare Diseases; Uterine Neoplasms
PubMed: 35144823
DOI: 10.1053/j.semdp.2022.01.006 -
Sarcoma 2018Leiomyomas of deep soft tissue are extremely rare and should only be diagnosed following adherence to stringent histological criteria, namely, the absence of nuclear... (Review)
Review
Leiomyomas of deep soft tissue are extremely rare and should only be diagnosed following adherence to stringent histological criteria, namely, the absence of nuclear atypia and of coagulative tumor necrosis. Whether extremely low counts of, or even any, mitotic activity are acceptable when making a diagnosis of leiomyoma in deep soft tissue sites is controversial. The morphology and immunophenotype of smooth muscle tumors in deep soft tissue are similar to their counterparts irrespective of topography. It is interesting to note that leiomyomas of deep soft tissue (extremity and retroperitoneum) are often hyalinized/sclerosed and calcified. However, the prediction of their behavior and correct codification is dependent on thorough, meticulous search for mitoses and necrosis. Leiomyomas of deep soft tissue in the extremity should be devoid of mitoses and "significant" cytological atypia. An occasional larger, slightly pleomorphic cell in the midst of bland spindle cells, can be regarded as insignificant atypia. If any mitotic activity and several atypical cells are encountered in smooth muscle tumors of deep soft tissue of the extremity, it would be prudent to invoke the appellation of smooth muscle tumor of uncertain malignant potential and advocate wide local excision and follow-up.
PubMed: 30271265
DOI: 10.1155/2018/2071394 -
Journal of Cytology 2023Endometrial aspiration (EA) is an economic, painless technique on an outpatient basis. Present study aimed at cytological evaluation of EA for (a) cellular yield and...
BACKGROUND
Endometrial aspiration (EA) is an economic, painless technique on an outpatient basis. Present study aimed at cytological evaluation of EA for (a) cellular yield and morphology and (b) utility of cell block (CB) and cytocentrifuge (CC) techniques.
MATERIALS AND METHODS
EA samples were divided into two aliquots. Colorless samples were processed (1000 rpm × 6 min) for conventional smear (CS) and CC, both stained by Papanicolaou. Hemorrhagic samples were processed for CS and CB (paraffin embedding, hematoxylin-eosin stain).
RESULTS
Endometrial aspirates from January 2021 to January 2022 were included. Indications comprised abnormal uterine bleeding (AUB; 87), prolapse (eight), and infertility (two). Among 77 hemorrhagic aspirates, the yield was 85.7% by CS and 90.9% by CB. Among 20 colorless aspirates, the yield was 55% by CS and 65% by CC. The yield was 85.7%, 84.4%, and 83.3% with endometrial thickness 1-5, 6-10, and 11-15 mm, respectively. The yield was 83.9%, 50%, and 0% in AUB, prolapse, and infertility, respectively. CS morphology showed the categories of benign (93.5%) and atypia (6.5%). All cases with benign morphology correlated with CB and CC. CB offered architectural evaluation, while CC had a shorter turnaround time.
CONCLUSION
Focusing on menorrhagia cases in secretory phase, nondilution of EA samples, and simultaneous endometrial biopsy can enhance cytology evaluation. In an era where "less should convey more," EA shows potential as a screening technique vis-à-vis invasive "dilatation-curettage" technique.
PubMed: 38058670
DOI: 10.4103/joc.joc_56_22 -
Lung Cancer (Auckland, N.Z.) 2018Fetal adenocarcinoma of the lung (FLAC) is a rare tumor. It accounts for ~0.1%-0.5% of all pulmonary neoplasms. Due to its rarity, much of the world literature regarding... (Review)
Review
Fetal adenocarcinoma of the lung (FLAC) is a rare tumor. It accounts for ~0.1%-0.5% of all pulmonary neoplasms. Due to its rarity, much of the world literature regarding FLAC comes from case reports and case series. FLAC is an adenocarcinoma resembling developing fetal lung in its pseudoglandular stage (8-16 weeks of gestation). It is distinguishable from pulmonary blastoma (PB) because it lacks the mesenchymal component which is a hallmark finding in PB. Due to differences in histopathology and clinical course, FLAC has been further categorized into low-grade (L-FLAC) and high-grade (H-FLAC) forms. L-FLAC displays low nuclear atypia and prominent morule formation and has a pure pattern. H-FLAC typically presents with at least 50% fetal morphology, and is often associated with other conventional types of lung adenocarcinoma. FLAC expresses neuroendocrine markers and thyroid transcription factor 1 in most cases. L-FLAC has an aberrant nuclear/cytoplasmic expression of β-catenin and presents mutations in this gene. H-FLAC overexpresses p53. These tumors have a very low frequency of mutations in and ; it is thought that they are different from a molecular point of view to conventional lung adenocarcinomas. Approximately 25%-40% of patients are asymptomatic at presentation; most of them are incidental findings on chest radiographs. H-FLAC is more common in elderly male patients, with a heavy smoking history. L-FLAC tends to occur in young females. Patients with L-FLAC are usually diagnosed with stage I-II disease, while patients with H-FLAC usually present with a more advanced-stage disease. Poor prognostic factors for FLAC are thoracic lymphadenopathy, metastases at diagnosis, and tumor recurrence; however, the 10-year survival for FLAC is estimated at 75%.
PubMed: 30197546
DOI: 10.2147/LCTT.S137410