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Background: Metastatic breast cancers are frequently encountered in cytology and require immunocytochemistry (ICC). In this study, traditional and multiplex ICC (mICC) for GATA‐binding protein 3 (GATA3), gross cystic disease fluid protein 15 (GCDFP15), and mammaglobin (MMG) were performed with the aim of validating mICC in cell blocks, with further single‐cell expression pattern analysis to identify the single markers and combinations of markers most sensitive in subtypes of breast cancer. Methods: GATA3, GCDFP15, and MMG were paired with OptiView 3,3′‐diaminobenzidine and Ventana DISCOVERY Purple and Blue, respectively, with cyclical and serial staining. Bright‐field imaging was performed with the Mantra 2 system and analyzed with the inForm Tissue Finder (Akoya Biosciences). Cell detection and phenotyping were further confirmed by two pathologists. Results: In the 36 cases studied, traditional ICC and mICC demonstrated good concordance (kappa coefficient, >0.5; p <.01) at three cutoffs (1%, 5%, and 50%), except for GATA3 at the 1% cutoff. Single‐marker positivity outnumbered double‐marker positivity and the exceedingly rare triple‐marker positivity (<3%). GATA3 was the leading single marker–positive phenotype in all breast cancer subtypes, except for MMG in estrogen receptor–positive, progesterone receptor–positive, and human epidermal growth factor receptor 2–positive (ER+/PR+/HER2+) breast cancers. Limited to two markers, GATA3/MMG included the greatest number of tumor cells for luminal breast cancers (ER+/PR+/HER2+, 60.6%; ER+/PR+/HER2+, 31.4%), whereas HER2‐overexpressed breast cancers (27.4%) and triple‐negative breast cancers (26.4%) favored the combination of GATA3/GCDFP15. Conclusions: For a single marker, GATA3 displayed the highest sensitivity. The addition of MMG for hormone receptor‐positive breast cancers and GCDFP15 for hormone receptor‐negative breast cancers further increased sensitivity. The low proportion of multimarker‐positive cells suggested that the coexpression observed with traditional ICC is attributable to intratumoral heterogeneity, not genuine coexpression. Traditional and multiplex immunocytochemistry (mICC) for GATA‐binding protein 3 (GATA3), gross cystic disease fluid protein 15 (GCDFP15), and mammaglobin (MMG) were performed with the aim of validating mICC in cell block preparations of metastatic breast cancer, with further single‐cell expression pattern analysis to identify the single markers and combinations of markers most sensitive in subtypes of breast cancer. For a single marker, GATA3 displayed the highest sensitivity. The addition of MMG for hormone receptor‐positive breast cancers and GCDFP15 for hormone receptor‐negative breast cancers further increased sensitivity. [ABSTRACT FROM AUTHOR]

Introduction : Cytological diagnosis of sarcomas requires detailed cytomorphological assessment and integration of immunocytochemistry and/or molecular testing. The role of exfoliative cytology, as compared to aspiration cytology, is less understood. This case series describes well-differentiated/dedifferentiated liposarcomas in effusions, with cytomorphological features, ancillary test results and clinical outcomes detailed. Methods : A computerized search of the department pathology archives was performed for sarcomatous effusions with histological diagnosis or clinical history of well-differentiated/dedifferentiated liposarcoma. Clinical progress, cytology slides, immunocytochemistry and molecular test results were reviewed. Results : Six patients were identified. In 5 patients with clinical follow up, 4 (80%) were deceased within 5 months of malignant effusion. One patient was alive with 12 years disease-free survival after radical resection with adjuvant radiotherapy. Three patients showed dedifferentiation on histology, and high-grade (dedifferentiated) tumor cells were present in effusion cytology of 2 patients. Two showed well-differentiated components only on biopsy, but high-grade (dedifferentiated) tumor cells were identified in cytology. The high-grade tumor cells displayed marked nuclear irregularity, enlargement, size variation, with macronucleoli and multinucleation. Well-differentiated lipomatous components were demonstrated in 4 patients (66.7%), comprising of multivacuolated lipoblasts and atypical lipocytes. CDK4 and MDM2 immunoreactivity in all 3 cases with cell blocks, and CDK4 and MDM2 amplification in one were successfully demonstrated. Conclusion : Lipomatous and dedifferentiated components can be sampled and cytomorphologically identified on effusion fluids of liposarcomas, with sufficient cellularity for immunocytochemistry and molecular testing. Although generally associated with poor prognosis, long disease-free survival with sarcomatous effusion is possible with radical surgery and adjuvant treatment. [ABSTRACT FROM AUTHOR]

Introduction: Compared with urothelial lesions of the upper urinary tract, the diagnostic performance of urine cytology in detection of renal cell carcinomas is underreported. This study aims to establish the role of urine cytology in the assessment of renal carcinomas by a multi‐institute review of urine cytology from nephrectomy confirmed renal cell carcinomas, referenced against renal urothelial and squamous cell carcinomas. Methods: Records of nephrectomy performed from the 1990s to 2020s at three hospitals were retrieved and matched to urine cytology specimens collected within 1 year prior. Patient demographics, specimen descriptors, and histology and staging parameters were reviewed and compared against cytologic diagnoses. Results: There were 1147 cases of urine cytology matched with renal cell carcinomas, with 666 renal urothelial/squamous carcinomas for comparison. The detection rate for urothelial/squamous (atypia or above [C3+]: 63.1%; suspicious or above [C4+]: 24.0%) were higher than renal cell carcinoma (C3+: 13.1%; C4+: 1.5%) (p < 0.001). The positive rate for upper tract urine exceeded other collection methods at 45.0% (C3+) and 10.0% (C4+) (p <.01). Other factors associated with increased positive rates were male sex, collecting duct carcinoma histology, nuclear grade, and renal/sinus involvement (p <.05). Multivariate analysis revealed additional positive correlations with presence of sarcomatoid tumor cells, lymphovascular invasion, and perinephric fat involvement (p <.05). Larger lesion size and higher urine volume did not improve detection rates (p <.05). Conclusions: The detection rate of renal cell carcinomas is suboptimal compared with urothelial carcinomas, although urine samples collected from cystoscopy or percutaneous nephrostomy significantly outperformed voided urine specimens. The detection rate of renal cell carcinomas is suboptimal compared with urothelial carcinomas, though urine samples collected from cystoscopy or percutaneous nephrostomy significantly outperformed voided urine specimens. [ABSTRACT FROM AUTHOR]

Introduction: Specific diagnosis of endometrial carcinomas on cervical cytology is difficult with few useful cytomorphological clues reported. This study reviews a cohort of cervical cytology to investigate the presence of keratinization in atypical glandular cells (AGC), an undescribed cytomorphological clue for identifying endometrial endometrioid carcinomas on cervical cytology. Methods: Cervical cytology slides from patients with a histologic diagnosis of endometrial endometrioid carcinoma were reviewed for the presence of keratinization associated with AGCs. Corresponding histology slides were reviewed for tumour grading and degree of squamous differentiation. Results: In total, 42 cases of cervical cytology specimens from 41 patients were retrieved, including 7 (16.7%) with keratinization associated with AGCs seen and 35 (83.3%) without. Comparison of histologic grading did not demonstrate an association with the presence of keratinization on cytology (p = 0.565). Corresponding histology slides were available for 37 cases. Cytologic and histologic keratinization were associated statistically (p = 0.002). Frank keratinization was seen on histologic slides of five cases, with four also showing cytologic keratinization. Area of squamous differentiation, including squamous morule formation, did not correlate with keratinization on cytologic preparation (p = 0.185). Conclusion: Histologic and cytologic keratinization are observed in endometrioid endometrial carcinomas. Such is reflected in cervical cytology by the presence of orangeophilic, rigid and acellular fragments within or associated with AGC clusters. Keratinization, when identified with AGCs, should be regarded as a cytologic clue suggestive of an endometroid carcinoma of endometrial origin. [ABSTRACT FROM AUTHOR]

Aspirates of liver abscess are frequently encountered in routine practice and are often of a low index of suspicion. However, necrotic liver metastasis clinically and radiologically mimics liver abscesses, and malignant cells can be obscured in an inflammation‐rich background on cytology. It is important to recognise malignant neoplasms in this scenario, in particular uncommon conditions such as metastatic mucosal melanoma. [ABSTRACT FROM AUTHOR]

Introduction: Endometrial lesions are morphologically diverse and uncommon on cervical smears, with its detection rate and associated diagnostic categories uncharacterized. In this study, cervical smears matched to histologically proven endometrial hyperplasias and carcinomas were reviewed and compared with cervical in‐situ‐carcinomas/carcinomas, aiming to detail the diagnostic performance of cervical smears for upper tract and glandular lesions. Methods: Pathology reports of cervical smears, hysterectomies, endometrial and cervical biopsies from 1995 to 2021 were retrieved. Diagnoses of cervical smears were matched to endometrial hyperplasias and carcinomas, or cervical carcinomas and reviewed. Results: Totally 832 cervical smears (272 cervical carcinomas, 312 endometrial carcinomas, and 248 hyperplasias) were included. Considering all cytologic glandular diagnosis as positive, the detection rate of cervical adenocarcinoma‐in‐situ was the highest (64.3%), followed by cervical adenocarcinoma (63.8%), endometrial carcinoma (31.7%), and hyperplasia (with atypia–8.5%; without atypia–2.3%) (p < 0.001). Endometrial hyperplasia was most often diagnosed as atypical squamous cells of undetermined significance (ASCUS) (5.0%) or atypical glandular cells, not otherwise specified (3.6%) without indication of endometrial origin. For endometrial carcinomas, higher FIGO grading and endocervical involvement were associated with higher detection rates across all diagnostic categories (p = 0.002–0.028). High FIGO grade was associated with suspicious/favor neoplastic (C4) (31.1%vs10.3%, p < 0.001) and carcinoma (C5) (17.8% vs. 5.6%, p = 0.005) categories, but not for all glandular diagnoses combined (33.3% vs. 31.0%, p = 0.761). Conclusion: Detection rates for endometrial lesions are lower than cervical lesions but not insignificant. Endometrial hyperplasia should be recognized as a differential of human papilloma virus‐negative ASCUS and prompt consideration of investigation of the upper genital tract. [ABSTRACT FROM AUTHOR]

Background: Pleural effusion can be caused by a wide range of benign and malignant conditions. Pleural biopsy and effusion cytology represent two key methods of pathological diagnosis. To compare the performance these two methods, a large cohort of matched pleural biopsy and effusion cytology with clinical follow‐up was reviewed. Methods: Pleural biopsies and effusion cytology specimens over a period of 18 years were retrieved. Cytology specimens collected within 7 days of pleural biopsy were matched. Reports were reviewed, and the cause for pleural effusion was determined by hospital disease coding and clinical data. Results: Totally, 3026 cases were included. The leading cause of benign effusion was tuberculosis (n = 650). Malignant pleural effusion (MPE) was more common in older females (p < 0.001) and mostly due to lung cancer (n = 959), breast cancer (n = 64), and mesothelioma (n = 48). The inadequate/insufficient (B1/C1) rate of biopsy was higher than cytology (15.6% vs. 0.3%) but the rates for other diagnostic categories were similar. Biopsy and cytology showed a correlation coefficient of 0.315, improving to 0.449 when inadequate/insufficient (B1/C1) cases were excluded. The ROM for benign cytology (C2) was lower than biopsy (B2) (p < 0.001). Compared with biopsy, the diagnostic accuracy was higher in cytology overall and for metastatic carcinomas (p < 0.001) but lower for hematolymphoid malignancies (p = 0.014) and mesotheliomas (p = 0.002). Conclusions: These results suggest that effusion cytology may be better for confirming benignity and diagnosing carcinomatous MPE. In these cases, pleural biopsy may be withheld to reduce procedural risks. However, for suspected hematolymphoid malignancies and mesothelioma, biopsy should be considered. [ABSTRACT FROM AUTHOR]

We thank Zhang and colleagues for their readership and letter.[[1]] Zhang et al. have commented that diagnostic odds ratio (DOR), negative-to-positive likelihood ratio (LR), and area under receiver operating characteristic curves (AUC) could serve additional metrics for exploring the diagnostic performance of pleural biopsy and pleural effusion, and that the lack of AUC constitutes methodological insufficiency. All subsequent analyses were based on two-by-two tables of pleural biopsies and pleural effusion cytology specimens. [Extracted from the article]

Bronchial exfoliative cytology is classified as non-abrasive (washing, aspiration and bronchoalveolar lavage) and abrasive (brushing). Brush abrasion dislodges epithelial cells but can induce bleeding and cytomorphologic artifacts. In this study, the largest cohort to date of bronchial cytology specimens were referenced against bronchial biopsy as the reference standard. Findings in the study will be useful for selecting biopsy modality and reducing necessary procedural risks. All consecutive bronchial cytology and bronchial biopsy from 1995 to 2022 were retrieved. The diagnoses were reviewed and categorized into five-tiered diagnostic categories to compare diagnostic agreement and concordance. Review of 14,148 specimens yielded 3963 non-abrasive, 2378 abrasive cytology specimens matched to biopsy, with 4355 matches between non-abrasive and abrasive cytology specimens. Agreement between non-abrasive and abrasive cytology was moderate (κ = 0.580), and similar when referenced against biopsy (κ = 0.456 (non-abrasive), κ = 0.498 (abrasive)). Abrasive bronchial cytology showed a higher percentage of malignant diagnosis (20.95 % vs. 12.63 %, p < 0.001) and over-diagnosis rate (36.40 % vs. 29.79 %, p < 0.001), but higher sensitivity (0.747 vs. 0.572, p = 0.002). For subgroup analysis of transbronchial biopsies, matched abrasive cytology showed higher discordant rates (p < 0.05) and lower accuracy (0.907 vs. 0.873, p = 0.020). With the added bleeding risk associated with brushing, abrasive techniques may only be preferable in cases with clinical or bronchoscopic suspicion of malignancy, in particular endobronchial mucosal lesions. For routine bronchoscopy, non-abrasive bronchial cytology appears to be adequate., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Neuroendocrine tumors of the lung display characteristic cytomorphologic features allowing direct diagnosis. The specificity of these features in distinguishing subtypes of neuroendocrine tumors, and their differences among types of cytologic specimen poses as interpretative potential pitfalls. This study reviewed and compared bronchial, effusion fluid and fine-needle aspiration cytology specimens of neuroendocrine tumors of the lung to address these issues. Histology-proven cytology specimens of neuroendocrine tumors were reviewed for cytomorphological parameters focusing on reported specific neuroendocrine nuclear and background features. Totally, 46 cases (26 bronchial, 11 effusion and 9 aspirate specimens), corresponding to 37 small cell carcinomas, 7 neuroendocrine carcinomas and 2 carcinoids were reviewed. Nuclear moulding (n = 35/37, 95 %), naked nuclei (n = 33/37, 89 %) and marked nuclear irregularity (n = 32/37, 86 %) were the three most common features of small cell carcinoma. The only specific feature for small cell carcinoma was the lack of prominent nucleoli (p = 0.004). For pulmonary carcinoids, in addition to the above features, other features associated with neuroendocrine carcinoma reviewed including crush artifact and necrotic material were absent. Compared to bronchial and aspiration cytology, crush artifact (p < 0.001) and necrotic material (p = 0.014) were absent on effusion fluid specimens and naked nuclei were less frequently seen (p = 0.022), while prominent nucleoli were more often observed (p = 0.005). Nuclear moulding, irregularity and naked nuclei are common but not unique features to small cell carcinomas. Effusion fluid specimens have "cleaner" backgrounds while displaying greater nuclear atypia. The type of cytologic preparation/specimen is an important factor which must be considered during diagnostic interpretation., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Fine-needle aspiration biopsy (FNAB) of the breast is an effective and widely adopted diagnostic technique. Histopathologic grading of ductal carcinoma in situ (DCIS) has prognostic significance. In this current study, FNAB of DCIS was reviewed to identify parameters that predict grading, histopathologic architecture, and presence of invasion in DCIS., Methods: Aspirates from histopathology-proven cases of DCIS were retrieved and reviewed for cytomorphologic parameters including cellularity, composition, epithelial fragment architecture cellular/nuclear features., Results: In total 104 aspirates were reviewed. Cytopathologic cellular features - large nuclear size (p = 0.005), prominent nucleoli (p = 0.011), increased nuclear membrane irregularity (p = 0.043), high variation in nuclear size (p = 0.025), and presence of apoptotic figures in epithelial structures (p &lt; 0.001); and background debris (p = 0.033) correlated with a high-grade diagnosis. Cytoplasmic vacuolation (p = 0.034) was seen exclusively in non-high-grade aspirates. Epithelial fragment architecture did not correlate with grading. A predominance (≥50%) of solid aggregates and papillary fragments on FNAB correlated with histopathologically solid (p = 0.039, p = 0.005) and papillary (p = 0.029, &lt; p = 0.001) patterns. No parameter showed correlation with invasion., Conclusion: FNAB is effective in predicting DCIS grading. Epithelial fragment architecture assessment is limited to papillary or solid types, and FNAB cannot predict focal invasion in DCIS., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Fine-needle aspiration cytology (FNAC) of lymph node is sensitive for detection of metastatic carcinoma but not without a significant false-negative rate. This study reviews clinicocytological features of negative node aspirates to identify predictive factors for establishing adequacy criteria., Methods: Negative FNAC specimens matched with neck dissection from a primary diagnosis of head and neck squamous cell, or undifferentiated (nasopharyngeal) carcinoma were reviewed for clinical and cytological parameters including lymphoid, inflammatory, and background components., Results: Slides from 86 lymph node aspirates including 50 positive for metastasis on follow-up were retrieved. Higher total lymphocyte count, lymphoid fragment count, germinal center fragment count, undifferentiated histology, presence of histiocytes and absence of blood were associated with a true negative cytologic diagnosis (p < 0.05), but not node size or location (p > 0.05). Undifferentiated histology, small lymphoid and germinal center fragments were independent factors indicative of a true negative diagnosis (p < 0.05). Large lymphoid fragments (p = 0.052) demonstrated a trend. Assessment of lymphoid components over five hotspots high-power fields (HPFs) was more robust in predictive value than only one hotspot. Receiver operating characteristic curve identified >10 small lymphoid, >20 large lymphoid and >2 germinal center fragment per five HPFs as optimal adequacy thresholds. Stricter total lymphocyte count cutoff accompanies increase of diagnostic accuracy, up to 0.67 for ≥5 HPFs with >500 lymphocytes., Conclusion: Total counts of lymphoid and germinal center fragments from multiple HPFs are useful in adequacy assessment of lymph node aspirates and improve diagnostic performance of FNAC in exclusion of metastatic carcinoma., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: The lung is an extensively epithelialized organ, producing ample exfoliated material for sputum and bronchial cytology. In view of the updates in the World Health Organization classification of early (T1/≤ 3 cm) lung cancer with respect to adenocarcinomas with lepidic pattern, this study retrospectively reviews sputum and bronchial cytology paired with resection-confirmed lung cancers., Methods: A computerized search for all lung resection specimens of carcinomas over a 20-year period was performed. Cytologic diagnoses of corresponding sputum and bronchial cytology were classified into five-tiered categories (C1-insufficient/inadequate, C2-benign, C3-atypia, C4-suspicious and C5-malignant). Reports and slides of the resection specimen were reviewed for reclassification of T1 cancers., Results: Totally 472 and 383 sputum and bronchial cytology specimens respectively were included. Sensitivity for T1 lesions on sputum cytology were 10.6 %, 2.1 % and 0.5 % at cutoffs of atypia/C3, suspicious/C4 and malignant/C5 categories, lower than bronchial cytology (35.1 %, 15.5 %, 8.1 %; p < 0.001). T1 lesions correlated with lower detection rates, whereas squamous cell carcinoma histology, larger size and bronchial invasion were associated with increased detection rates in sputum and bronchial cytology (p < 0.050). Detection rates for abrasive bronchial cytology (brushing) were overall higher (p = 0.018- < 0.001), but on subgroup comparison, non-abrasive (aspiration, lavage and washing) cytology demonstrated favorable trends (p = 0.063-0.088) in detecting T1 lesions. Adenocarcinomas with lepidic pattern had lower suspicious/C4 (p = 0.040) or above and malignant/C5 (p = 0.019), but not atypia/C3 or above (p = 0.517) rates., Conclusions: Most adenocarcinomas with lepidic pattern are only diagnosed as atypia/C3 on cytology. With its modest sensitivity, interpretation of negative and indeterminate cytology results mandates caution., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Pulmonary adenoid cystic carcinoma (AdCC) is a central and superficial primary lung neoplasm, well-suited for sampling by bronchial cytology. This study aims to review the cytologic features of pulmonary AdCC on bronchial cytology, and to report an experience of applying immunocytochemistry on this rare entity., Methods: A multi-institute review of bronchial cytology specimens from histologically proven pulmonary AdCCs was performed. Published cases of bronchial cytology of pulmonary AdCC were reviewed. The cytologic features and immunocytochemical profile for pulmonary AdCC was summarized and compared with pertinent differentials., Results: A total of 16 specimens from eight patients were retrieved. The initial cytologic diagnoses were negative (n = 7), atypia (n = 6), suspicious (n = 2) and AdCC (n = 1). Retrospective review showed eight bronchial cytology specimens (including five cases of atypia) with tumor cells present. The tumor cells displayed small basaloid nuclei with occasional small nucleoli, mild nuclear atypia, and scanty cytoplasm. Architectural patterns observed included clusters, tubules, solid sheets, three-dimensional balls, papillary-like fronds, and complex cribriform structures. Basement-membrane-like material, free or associated with tumor cells, were seen in all cases. Immunocytochemistry was performed in one specimen. MYB was positive. TTF-1, synaptophysin and chromogranin were negative. Epithelial and basal markers demonstrated a dual cell population. Literature review yielded 28 cases. Cytologic features described were similar except for cytoplasmic vacuolation in one case., Conclusion: Basement membrane-like material is specific for AdCC. MYB positivity, TTF-1 and neuroendocrine marker negativity, support a diagnosis of AdCC. Other immunocytochemistry and cytologic features overlap significantly with adenocarcinoma and small cell carcinoma of lung., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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 nonsalivary gland myoepithelial cells. 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). The stained slides were digitized and orientated with H&E images and assessed simultaneously using QuPath. A total of 129, 58, and 56 breast, cutaneous, and salivary gland lesions, respectively, were included. There was poor agreement between WT1-p63 and WT1-calponin (κ < 0.1) in all organs, with absence of WT1 expression in normal salivary gland myoepithelium and most ACCs. There were no significant differences in WT1 expression in myoepithelial cells in normal breast tissue and benign breast neoplasms. Compared to pleomorphic adenomas, cutaneous mixed tumors showed lower WT1 expression (P < .001). WT1 is a less sensitive myoepithelial marker than calponin and p63. However, its unique pattern of expression in salivary gland primary for pleomorphic adenomas/cutaneous mixed tumor can favor a diagnosis of benign salivary gland tumors, particularly in small biopsy specimens., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Idiopathic granulomatous mastitis (IGM) is a benign mimic of breast carcinomas. It is defined histologically by the presence of granulomas and inflammation. The closely related cystic neutrophilic granulomatous mastitis (CNGM) shows lipogranulomas, with a reported association with corynebacteria. A large cohort of IGM was reviewed to compare clinical, microbiological and histological features between non-CNGM IGM and CNGM. Cases of IGM were reviewed for histological parameters including the presence of lipogranulomas and composition of inflammatory cells. Clinical data were obtained through hospital records. The cohort included 79 cases, including 51 non-CNGM IGM and 28 CNGM. Comparing non-CNGM IGM and CNGM, there were no differences in clinical or demographical data, other than a younger age of presentation (36.2 vs 41.5 years, p=0.012) for CNGM. Most IGM resolved within the follow-up period (n=57/64, 89.1%), with similar outcomes regardless of treatment (p>0.05). In CNGM, there were more infiltrates of neutrophils (p=0.001), histiocytes (p=0.047), and multinucleated giant cells (p=0.006), but less lymphocytes (p=0.008). Corynebacteria was cultured in two (25%) cases of CNGM, and one non-CNGM IGM (14.3%). Gram-positive bacilli were identified in two cases of CNGM. 'Early' lipogranulomas were observed closely associated to inflamed ducts in three cases of CNGM. Apart from age, there was no distinct clinical or microbiological feature for CNGM. These findings do not support CNGM as a distinct entity. Rather, CNGM-pattern may represent a continuum of IGM, possibly age-related and attributable to ductal inflammation and cystic changes in the breast parenchyma., (Copyright © 2022 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Introduction: Increasing molecular evidence indicates that tubular adenoma of the breast is distinct from fibroepithelial lesions, leading to its reclassification as an epithelial tumor in the 5th World Health Organization classification of tumors of the breast. However, tubular adenoma remains poorly characterized on fine-needle aspiration cytology (FNAC) and often not distinguished from fibroadenomas. In this study, the largest cohort, to date, of histologically confirmed aspirates of tubular adenomas were reviewed and compared with aspirates of fibroadenomas. Findings from this study further define the cytological features of tubular adenoma and allow differentiation from fibroadenoma., Methodology: Aspirates of histologically confirmed tubular adenomas were reviewed for features of the background, myoepithelial, epithelial, and stromal components and then compared to a cohort of aspirates of fibroadenomas., Results: Totally, 43 (tubular adenoma) and 94 (fibroadenoma) aspirates were included. Tubular adenomas displayed moderate epithelial cellularity with high cohesiveness, with stromal fragments containing epithelium. Tubules are more common in tubular adenomas (p = 0.009) and "tubular fragments" (tissue fragments containing multiple tubular structures with/without stroma) is a pathognomonic feature of tubular adenoma (p < 0.001). Calcification and fibrocystic changes were variably seen (4.65-13.5%) but without difference to fibroadenomas (p > 0.05). Cytomorphologically malignant features and mitoses were absent in all aspirates of tubular adenoma. Presence of tubules and stromal fragments were independent factors associated with tubular adenomas, whereas a predominance of large epithelial fragments and naked stromal fragments were associated with fibroadenomas., Conclusion: Tubular adenomas are not only histologically and molecularly separate from fibroepithelial lesions but also a distinct entity on FNAC., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

The use of immunostain for PRAME antigen is well established for cutaneous melanolocytic lesions. However, its staining in other cutaneous structures and lesions is under reported. This study assessed PRAME staining in a large cohort of normal skin tissue, sebaceous lesions, and cutaneous carcinomas to better delineate patterns of PRAME immunoreactivity. PRAME immunostaining was performed on sections of sebaceous lesions and tissue microarrays of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs). Normal cutaneous adnexal structures were assessed on the sections of sebaceous lesions. For sebaceous lesions and non-lesional sebaceous glands, PRAME immunostaining was assessed for mature, germinative and sebocytes independently. A total of 193 sebaceous lesions, 64 BCCs and 35 SCCs were stained for PRAME immunostain. Staining pattern was predominantly cytoplasmic in normal apocrine glands, germinative sebocytes of sebaceous glands, and hair germs (p<0.001). Lesional sebocytes did not show different staining compared to normal sebaceous glands (p>0.05). Rare nuclear staining was observed in the normal epidermis (0.6%) and junctional melanocytes (4.1%). BCC, SCC and sebaceous carcinoma all showed low levels of PRAME immunoreactivity with variable proportions of cases demonstrating nuclear staining (BCC 59.4%, SCC 37.1%, sebaceous carcinoma 5.3%). PRAME immunostaining is positive in germinative sebocytes, various cutaneous structures and carcinomas. Nuclear staining, identical to melanoma, was observed in normal epidermis, junctional melanocytes, BCCs, SCCs, and sebaceous carcinomas. The pattern of PRAME staining in the skin must be recognised to avoid pitfalls in interpretating PRAME immunostain., (Copyright © 2022 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Oncocytic metaplastic lesions of the nasopharynx are rare benign entities which are divided into melanotic and non-melanotic forms. Less than 40 non-melanotic and 30 melanotic cases have been reported in the literature. We present the largest known case series to date of melanotic oncocytic metaplasia and more than 20 cases of non-melanotic oncocytic metaplasia. Clinical, endoscopic, histological and immunohistochemical features were reviewed. Most cases presented in males starting from their late adulthood. Compared to its non-melanotic counterpart, all cases of melanotic oncocytic metaplasia had a smoking history (p=0.041). All cases of melanotic oncocytic metaplasia were negative to melanocytic markers (S100, HMB-45, Melan-A and MiTF). Although no disease-related mortality was recorded, concurrent melanoma and nasopharyngeal carcinoma were seen in two cases., (Copyright © 2019 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)