Apocrine Differentiation Research Articles

Syringocystadenoma Papilliferum-Like Features in Poroma: An Unusual Morphologic Pattern of Poroma or True Synchronous Occurrence of 2 Distinct Neoplasms?

Poromas are benign adnexal neoplasms of eccrine origin, believed to arise from the outer layer of acrosyringia and upper dermal eccrine ducts, with a predilection for glabrous skin. They typically present as a pink or red papule with a surrounding thin moat on the palms and soles. We report a case of poroma with histopathologic features reminiscent of syringocystadenoma papilliferum (SCAP). A 70-year-old woman presented with a 2.0 cm pedunculated nodule on the left suprapubic abdomen. Histopathologically, the lesion predominantly displayed features of a conventional poroma but also included areas with endophytic invaginations lined by large, plump epithelioid cells with abundant eosinophilic cytoplasm and occasional decapitation secretion, alongside a stroma rich in plasma cells-characteristics suggestive of SCAP. However, definitive bilayers with myoepithelial cells were not observed. Immunohistochemical studies revealed that the tumor cells were positive for TRPS1 (particularly around SCAP-like areas) and CEA (indicating ductal differentiation), but negative for BRAF V600E and NUT. The diagnosis of poroma with apocrine differentiation mimicking SCAP was favored. This unusual morphologic variation in poromas is rare, with fewer than 5 cases documented in the literature. These SCAP-like features likely represent a variation within the morphologic spectrum of poromas rather than the presence of 2 synchronous tumors. Our case highlights the importance of recognizing such variations in poroid neoplasms to ensure accurate diagnosis.

The relationship between tumor immunity and the cGAS–STING pathway in breast cancer: An immunohistochemical study

Breast cancer (BC) is classified into four major histological subtypes, namely luminal A, luminal B, HER2, and basal-like, and its treatment is based on these subtypes. The use of immune checkpoint inhibitors against BC depends on the expression of PD-1/PD-L1. Another tumor immune system—the cGAS–STING pathway—is a potential target for cancer immunotherapy. However, the status of the cGAS–STING pathway in BC has not been fully established. Therefore, we investigated the expression status of the cGAS–STING pathway and immune-related proteins in BC. We classified 111 BCs into six groups—29 hormone receptor-positive carcinomas, 12 HER2+ carcinomas (HER2), 8 luminal-HER2 carcinomas, 26 triple-negative breast carcinomas (TNBCs), 21 lobular carcinomas (LC), and 15 carcinomas with apocrine differentiation (CAD)—and investigated the relationship between BC and tumor immunity via the cGAS—STING pathway using histopathological and immunohistochemical methods. Expression of cGAS was high in CADs (100%) and low in TNBCs (35%); STING-positive lymphocytes were high in TNBC (85%, P = 0.0054). Expression of pSTAT3 was significantly high in patients with TNBC (≥10%, 88%). The proportion of PD-L1-positive tumor cells was higher in TNBCs (54%) than in other BCs (30%). SRGN expression was significantly higher in the TNBC group than in the other BC groups (58%). Tumor immune responses may differ among tumor subtypes. The cGAS–STING pathway may be functional in TNBC and CAD but not in LC. Therefore, targeting the cGAS–STING pathway might be useful in BC, particularly TNBC and CAD.

Neoadjuvant Chemotherapy Response in Triple-Negative Apocrine Carcinoma: Comparing Apocrine Morphology, Androgen Receptor, and Immune Phenotypes.

Apocrine differentiation and androgen receptor (AR) positivity represent a specific subset of triple-negative breast cancer (TNBC) and are often considered potential prognostic or predictive factors. To evaluate the response of TNBC to neoadjuvant chemotherapy (NAC) and to assess the impact of apocrine morphology, AR status, Ki-67 labeling index (Ki-67LI), and tumor-infiltrating lymphocytes (TILs). A total of 232 TNBC patients who underwent NAC followed by surgical resection in a single institute were analyzed. The study evaluated apocrine morphology and AR and Ki-67LI expression via immunohistochemistry from pre-NAC biopsy samples. Additionally, pre-NAC intratumoral TILs and stromal TILs (sTILs) were quantified from biopsies using a deep learning model. The response to NAC after surgery was assessed based on residual cancer burden. Both apocrine morphology and high AR expression correlated with lower Ki-67LI (P < .001 for both). Apocrine morphology was associated with lower postoperative pathologic complete response (pCR) rates after NAC (P = .02), but the difference in TILs between TNBC cases with and without apocrine morphology was not statistically significant (P = .09 for sTILs). In contrast, AR expression did not significantly affect pCR (P = .13). Pre-NAC TILs strongly correlated with postoperative pCR in TNBCs without apocrine morphology (P < .001 for sTILs), whereas TNBC with apocrine morphology demonstrated an indeterminate trend (P = .82 for sTILs). Although TIL counts did not vary significantly based on apocrine morphology, apocrine morphology itself was a more reliable predictor of NAC response than AR expression. Consequently, although apocrine morphology is a rare subtype of TNBC, its identification is clinically important.

Detection of TROP2: Ushering in a new choice in the treatment of patients with special types of invasive breast cancer.

1106 Background: TROP2 has become an attractive new therapeutic target in breast cancer (BC). TROPiCS-02 trial shows that the sacituzumab govitecan(SG) which is the TROP2 ADC drug can significantly benefit the survival of patients with TNBC and HR+/HER2- BC, and the 2023 ASCO guideline recommends that TROP2 detection is not necessary before the SG treatment. However, less than 5% BC patients of special subtype were included in clinical trials, and the TROP2 expression of them is not yet known. The aim of our study is to compare the expression of TROP2 in different special types of BC, and provide reference for targeted treatment of these patients. Methods: We retrospectively retrieved tissues from 383 patients diagnosed with special type of BC and undergoing surgical resection at our institution from 2018 to 2023. Including metaplastic carcinoma (MBC), mucinous carcinoma (MC), adenoid cystic carcinoma, cribriform carcinoma, carcinoma with apocrine differentiation, neuroendocrine carcinoma and tubular carcinoma. Classify them as TNBC or HR+/HER2- BC. Applying H-score to evaluate the TROP2 expression, H-score&lt;100, 100~200, and 201~300 classified as low, moderate and high expression. Results: Expression of TROP2 is higher in tubular and cribriform carcinoma, while in MBC and MC is significantly lower (χ2=66.756, P&lt;0.001) (Table). Low expression of TROP2 is associated with low clinical staging ( P&lt;0.05), no lymph node metastasis ( P&lt;0.05), and high-grade tumor infiltrating lymphocytes ( P&lt;0.05). Moreover, TROP2 had the lowest expression in MBC, with a median H-score of 45. There are 78.13% (43/55) cases showed H-score&lt;100, with 27.3% (15/55) of cases showing no expression of TROP2 at all. It is worth noting that MBC is highly invasive and has a poor prognosis, but the expression level of TROP2 is very low in mesenchymal cells, while in squamous differentiated tumor tissue, the expression level of TROP2 is high, and the overall H-Score score is low ( P&lt;0.001). Conclusions: This study is the first preliminary study on the TROP2 expression in special types of breast cancer. Although the current ASCO guideline recommends not testing TROP2, but our study shows it is pretty low or even not expressed in MBC and MC. Notably, the lack of expression in the mesenchymal and spindle cell subtypes may be highly indicates that they lack epithelial tumor cells expressing TROP2 as vectors, resulting in the inability to exert the therapeutic effect of ADC, we suggest routine testing of TROP2. [Table: see text]

Abstract PO3-08-05: Prognostic value of multigene test to the patients with Hormone receptor-positive, HER2-negative breast cancer based on special histologic subtypes

Abstract Background: Special histologic subtypes of breast cancer, including mucinous and tubular, account for 25% of all invasive breast cancers. Multigene tests (MGT) play a crucial role in guiding adjuvant chemotherapy and predicting prognosis for the patients with Hormone receptor-positive HER2-negative breast cancer. This research aims to examine the results of multigene tests for special histologic subtype patients and review the prognosis of each group. Methods: A retrospective analysis was conducted on data from 133 patients with special histologic subtypes of breast cancer who underwent surgery at Severance Hospital between November 2013 and December 2022. Each patient underwent one type of MGT, including Oncotype Dx, MammaPrint, or EndoPredict. Patients were grouped in two groups according to histologic types, based on WHO classification. Favorable types consist of type A mucinous carcinoma, pure tubular carcinoma, invasive solid papillary carcinoma, encapsulated papillary carcinoma with invasion, invasive cribriform carcinoma, secretory carcinoma, and invasive carcinoma with apocrine differentiation. Unfavorable types included type B mucinous carcinoma, mucinous carcinoma with micropapillary feature or neuroendocrine differentiation, mixed IDC, ILC or invasive micropapillary carcinoma, mixed invasive solid papillary carcinoma, mixed invasive papillary carcinoma, and mixed invasive cribriform carcinoma with IDC. Results: Patients with favorable types accounted for 42.86% (57 patients), while patients with unfavorable types accounted for 57.14% (76 patients). Patients with unfavorable histologic subtypes of breast cancer tended to have a higher incidence of high-risk results in MGT, as well as a greater prevalence of multiple (multifocal, multicentric) cancer and higher histologic grade. In multivariate analysis using logistic regression, unfavorable types showed a significantly high ratio of having high risk on MGT compared to the favorable type (OR = 4.327, 95% CI 1.210 – 15.475, p-value = 0.024). Moreover, overall survival in unfavorable histologic types showed a statistically significant difference between high-risk and low-risk in Kaplan-Meier survival analysis (p-value = 0.001). Conclusions: Unfavorable subtypes have shown a significantly higher-risk result of MGT, and patients with unfavorable types of breast cancer and high-risk MGT results have exhibited the worst prognosis. Consequently, we can suggest that MGT can be used as a prognosis evaluation tool for certain special subtypes of breast cancer and further utilized to aid in treatment decisions. Citation Format: Seung Hye Yang, Jee Hyun Ahn, Suk Jun Lee, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong Woo Park, Seho Park. Prognostic value of multigene test to the patients with Hormone receptor-positive, HER2-negative breast cancer based on special histologic subtypes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-05.

Case Report: Thigh hidradenoma masquerading as lipoma

Background: Hidradenomas are benign adnexal neoplasms which were recently been subdivided into two groups: eccrine differentiation (poroid hidradenomas) or apocrine differentiation (clear cell hidradenomas) with the latter being rarer. These types of tumors have been associated with recurrence and malignant transformation, however; recurrence and malignancy are considered very rare. We present a case report of a 35-year-old male who presented with two lumps, clinically representing simple lipomas but one of them turned to be a hidradenoma.

Diagnostic utility and sensitivities of matrix Gla protein (MGP), TRPS1 and GATA3 in breast cancer: focusing on metastatic breast cancer, invasive breast carcinoma with special features, and salivary gland-type tumours

Matrix Gla protein (MGP) and trichorhinophalangeal syndrome type 1 (TRPS1) have recently emerged as novel breast-specific immunohistochemical (IHC) markers, particularly for triple-negative breast cancer (TNBC) and metaplastic carcinoma. The present study aimed to validate and compare the expression of MGP, TRPS1 and GATA binding protein 3 (GATA3) in metastatic breast carcinoma (MBC), invasive breast carcinoma (IBC) with special features, including special types of invasive breast carcinoma (IBC-STs) and invasive breast carcinoma of no special type with unique features, and mammary and non-mammary salivary gland-type tumours (SGTs). Among all enrolled cases, MGP, TRPS1 and GATA3 had comparable high positivity for ER/PR-positive (p=0.148) and HER2-positive (p=0.310) breast carcinoma (BC), while GATA3 positivity was significantly lower in TNBC (p<0.001). Similarly, the positive rates of MGP and TRPS1 in MBCs (99.4%), were higher than in GATA3 (90.9%, p<0.001). Among the IBC-STs, 98.4% of invasive lobular carcinomas (ILCs) were positive for all three markers. Among neuroendocrine tumours (NTs), all cases were positive for TRPS1 and GATA3, while MGP positivity was relatively low (81.8%, p=0.313). In the neuroendocrine carcinoma (NC) subgroup, all cases were positive for GATA3 and MGP, while one case was negative for TRPS1. All carcinomas with apocrine differentiation (APOs) were positive for GATA3 and MGP, while only 60% of the cases demonstrated moderate staining for TRPS1. Among mammary SGTs, MGP demonstrated the highest positivity (100%), followed by TRPS1 (96.0%) and GATA3 (72.0%). Positive staining for these markers was also frequently observed in non-mammary SGTs. Our findings further validate thehigh sensitivity of MGP and TRPS1 in MBCs, IBC-STs, andbreast SGTs. However, none of these markers arecapable of distinguishing between mammary and non-mammary SGTs.

Malignant Adnexal Carcinoma of the Face: A Case Report

Malignant adnexal tumors (MAT) form a group of rare, typically low-grade- malignancy carcinomas with follicular, sebaceous, apocrine, or eccrine differentiation or a combination of the first 3 subtypes, the biopsy is required to establish the differentiation subtype and the definitive diagnosis. our case is a 67 years old female presented to our department of maxillofacial surgery of Ibn Sina hospital in Rabat with a left frontal skin lesion that had begun evolving 6 months ago. An excisional biopsy was performed afterwards using an elliptical excision with 1 cm of margins laterally and including the periost deeply, and then the sking defect was sutured in 3 layers. Malignant pilosebaceous tumors are more rare, especially those of the hair follicle. Sebaceous gland carcinoma commonly arises in the periorbital area. Surgical resection is the most commonly implemented treatment modality in MATs.

Poroid Neoplasms: A Clinicopathological Study of 13 Cases.

Poroid neoplasms (PN) are a heterogeneous group of tumors deriving from sweat glands and folliculo-sebaceous units. Their histological classification and clinical features are challenging. Our aim was to report clinicopathological features of poroid neoplasms. It is a retrospective study including all cases of poroid neoplasms registered at our Pathology laboratory of Niamey National Hospital (February 2020-February 2024). We registered 13 cases of benign poroid neoplasms: 10 classic poromas (CP) (76.9%), 2 poroid hidradenomas (PH) (15.4%) and 1 dermal duct tumor (DDT) (7.7%). Nine cases (69.2%) had preoperative clinical diagnosis of malignancy. The mean age was 41.1 years (range of 12-70 years) with a slight female predominance. Only 4/13 cases (30.8%) had classical palmoplantar locations. The tumors mean size was 3.7 cm (range of 0.4-8 cm). Clear cells were present in 7 cases (53.8%), apocrine ductal differentiation (mixed or pure) in 6 cases (46.2%), keratin horns in 2 cases (15.4%), squamous eddies in 6 cases (46.2%), melanin pigments in 1 case (7.7%) and sebaceous differentiation in 2 cases (15.4%). Unlike what is classically reported, our study shows that apocrine ductal differentiation, younger age and non-palmoplantar locations are common in poroid neoplasms.

Cytomorphological features of syringocystadenoma papilliferum mimicking pilomatricoma at a rare location and in an unusual age group: A cytological diagnostic challenge.

Syringocystadenoma papilliferum (SCAP) is a rare, benign skin adnexal tumor of apocrine or eccrine differentiation usually occurring in the head and neck region of children. It is a difficult entity to diagnose clinically and even cytological diagnosis remains challenging due to overlapping and masquerading cyto-morphological features with other benign cutaneous adnexal tumors. Here we present, one such intriguing case of SCAP with its cytological features mimicking those of pilomatricoma. Moreover, the lesion was located at the right lower abdomen, which in itself is a rare site and its presentation was in an adult male which is an unusual age group. However, fine needle aspiration cytology still remains a very useful investigation for cutaneous tumors as it helps in differentiating benign lesions from malignant and metastatic neoplasms and therefore aids in correct treatment and follow-up of patients.

Prognostic Role of Prolactin-Induced Protein (PIP) in Breast Cancer.

Prolactin-inducible protein (PIP), also referred to as gross cystic disease fluid protein 15 (GCDFP-15), has been a trending topic in recent years due to its potential role as a specific marker in breast cancer. PIP binds to aquaporin-5 (AQP5), CD4, actin, fibrinogen, β-tubulin, serum albumin, hydroxyapatite, zinc α2-glycoprotein, and the Fc fragment of IgGs, and the expression of PIP has been demonstrated to be modulated by various cytokines, including IL4/13, IL1, and IL6. PIP gene expression has been extensively studied due to its captivating nature. It is influenced by various factors, with androgens, progesterone, glucocorticosteroids, prolactin, and growth hormone enhancing its expression while estrogens suppress it. The regulatory mechanisms involve important proteins such as STAT5A, STAT5B, Runx2, and androgen receptor, which collaborate to enhance PIP gene transcription and protein production. The expression level of PIP in breast cancer is dependent on the tumor stage and subtype. Higher expression is observed in early-stage tumors of the luminal A subtype, while lower expression is associated with luminal B, basal-like, and triple-negative subtypes, which have a poorer prognosis. PIP expression is also correlated with apocrine differentiation, hormone receptor positivity, and longer metastasis-free survival. PIP plays a role in supporting the immune system's antitumor response during the early stages of breast cancer development. However, as cancer progresses, the protective role of PIP may become less effective or diminished. In this work, we summarized the clinical significance of the PIP molecule in breast cancer and its potential role as a new candidate for cell-based therapies.

DNA Methylation Identifies Epigenetic Subtypes of Triple-Negative Breast Cancers With Distinct Clinicopathologic and Molecular Features

Triple-negative breast cancers (TNBC) include diverse carcinomas with heterogeneous clinical behavior. DNA methylation is a useful tool in classifying a variety of cancers. In this study, we analyzed TNBC using DNA methylation profiling and compared the results to those of mutational analysis. DNA methylation profiling (Infinium MethylationEPIC array, Illumina) and 50-gene panel–targeted DNA sequencing were performed in 44 treatment-naïve TNBC. We identified 3 distinct DNA methylation clusters with specific clinicopathologic and molecular features. Cluster 1 (phosphoinositide 3-kinase/protein kinase B–enriched cluster; n = 9) patients were significantly older (mean age, 71 years; P = .008) with tumors that were more likely to exhibit apocrine differentiation (78%; P < .001), a lower grade (44% were grade 2), a lower proliferation index (median Ki-67, 15%; P = .002), and lower tumor-infiltrating lymphocyte fractions (median, 15%; P = .0142). Tumors carried recurrent PIK3CA and AKT1 mutations and a higher percentage of low HER-2 expression (89%; P = .033). Cluster 3 (chromosomal instability cluster; n = 28) patients were significantly younger (median age, 57 years). Tumors were of higher grade (grade 3, 93%), had a higher proliferation index (median Ki-67, 75%), and were with a high fraction of tumor-infiltrating lymphocytes (median, 30%). Ninety-one percent of the germline BRCA1/2 mutation carriers were in cluster 3, and these tumors showed the highest level of copy number alterations. Cluster 2 represented cases with intermediate clinicopathologic characteristics and no specific molecular profile (no specific molecular profile cluster; n = 7). There were no differences in relation to stage, recurrence, and survival. In conclusion, DNA methylation profiling is a promising tool to classify patients with TNBC into biologically relevant groups, which may result in better disease characterization and reveal potential targets for emerging therapies.

Clinicopathologic and Immunophenotypic Classification of Invasive Lobular Carcinoma with Histiocytoid Features.

Histiocytoid lobular breast carcinoma is a rare subtype of invasive lobular carcinoma characterized by relatively bland, uniform nuclei, single small eosinophilic nucleolus, and ample granular cytoplasm. These cancers are typically triple negative, show frequent androgen receptor (AR) positivity, and are therefore theorized to represent a variant of apocrine differentiation in invasive lobular carcinoma. Anecdotal evidence suggests that these tumors have excellent outcomes, though some studies suggest a variable clinical outcome. Inclusion criteria included women with a histologic diagnosis of invasive lobular carcinoma with histiocytoid features, regardless of immunohistochemical profile, diagnosed at our institution between 2008 and 2021 with additional tissue still available for ancillary studies. We reviewed patients meeting these criteria and investigated hematoxylin and eosin-stained slides and a panel of immunohistochemical stains (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 [HER2], AR, endothelial growth factor receptor, and keratin 5/6), as well as outcomes including survival and metastatic disease. Overall, 12 eligible patients were identified. The classical immunophenotype (triple negative with AR positivity) was noted in 4 out of 12 tumors. The majority of the remaining tumors (7 out of 12) showed a luminal B immunohistochemical profile, while 1 out of 12 was HER2-enriched. No patients in the cohort died from disease-related causes and 2 out of 12 presented with distant metastatic disease during their disease course. Histiocytoid lobular breast carcinoma is a morphologic variant of lobular carcinoma with apocrine features that shows a variable immunohistochemical profile and variable clinical behavior. Further subclassification and stricter diagnostic criteria may be helpful in the distinction between truly indolent tumors and those with more aggressive clinical features.

Histomorphological patterns of skin adnexal tumours with an insight into molecular updates - A single institutional study

Background: Skin adnexal tumors are a spectrum of benign and malignant tumors that differentiate toward or arise from the adnexal unit of the skin. These rare tumors pose a challenge in diagnosis, and often, a discrepancy is seen between clinical and histopathological diagnosis. Materials and methods: This single institutional study was carried out among 36 patients who presented with swelling. An initial diagnosis was considered based on the clinical history followed by histopathological examination. Results: Among the 36 patients, only 4 had malignant tumors. Among them, 3 had sebaceous differentiation, and 1 had apocrine and eccrine differentiation. Among the benign, 14 had follicular differentiation, 12 had apocrine and eccrine differentiation, and 6 had sebaceous differentiation. The clinic-pathological correlation was 65%. Conclusions: An accurate diagnosis is not possible with just the clinical features. Histopathologic examination is considered the gold standard for diagnosis and categorization.

Immunohistochemical Characterization of a Large Cohort of Triple Negative Breast Cancer.

Introduction. Triple negative breast carcinomas are characterized by a lack of hormone receptor and HER2 expression and inconsistent expression of breast-specific immunohistochemical markers. The expression of many site-specific markers in these tumors is largely unknown. The objective of the study was to examine the expression of widely used immunohistochemical markers on a large cohort of triple negative breast cancer. Methods. Sections from tissue microarrays were stained with 47 markers using routine protocols. Most markers were scored using a modified Allred method. ATRX, BAP1, SMAD4, e-cadherin, and beta-catenin were scored as retained or lost. Mammaglobin was considered positive if there was at least moderate intensity staining in any tumor cells. P16 was scored as overexpressed or not overexpressed; p53 was scored as wildtype, overexpressed, null, or cytoplasmic. Results. The cohort consisted of 639 tumors including 601 primary and 32 metastases. Overall, 96% expressed GATA3, mammaglobin, and/or SOX10 while 97% of no special type tumors expressed this panel. Carcinoma of apocrine differentiation demonstrated an AR positive, SOX10 negative, K5 negative/focal immunophenotype. PAX8 (SP348), WT1, Napsin A, and TTF1 (8G7G3/1) were never or rarely expressed while CA9, CDX2, NKX3.1, SATB2 (SATBA410), synaptophysin, and vimentin were variably expressed. Conclusions. Almost all TNBC express at least 1 of the 3 IHC markers: GATA3, mammaglobin, and/or SOX10. Carcinoma of apocrine differentiation is characterized by an AR positive, SOX10 negative, K5 negative or focal immunophenotype. Cautious interpretation of so-called site-specific markers, with knowledge of antibody clones, is required in excluding the diagnosis of triple negative breast cancer.

A RARE CASE REPORT ON TUBULAR APOCRINE ADENOMA

Tubular apocrine adenoma, the apocrine variant of papillary tubulopapillary hidradenoma, is a rare well-circumscribed, intradermal benign tumor, with tubular structures showing apocrine differentiation. It usually presents as a slow-growing well-circumscribed nodule. The most common site of involvement is the scalp, although it has also been reported to occur at other sites like face, neck, axilla, trunk, upper and lower extremities. The present study describes a case of 76-year-old female who presented with swelling on back. An excisional biopsy was performed which on histopathological examination shows multiple irregular-shaped tubular structures lined by two layers of epithelial cells focally. On histopathology, the case was diagnosed as tubular apocrine adenoma.

Recurrent PAK2 rearrangements in poroma with folliculo-sebaceous differentiation.

Poroma is a benign adnexal neoplasm with differentiation towards the upper portion of the sweat gland apparatus. In 2019, Sekine etal. demonstrated recurrent YAP1::MAML2 and YAP1::NUTM1 fusion in poroma and porocarcinoma. Follicular, sebaceous and/or apocrine differentiation has been reported in rare cases of poroma and whether these tumours constitute a variant of poroma or represent a distinctive tumour is a matter to debate. Herein we describe the clinical, immunophenotypic, and molecular features of 13 cases of poroma with folliculo-sebaceous differentiation. Most of the tumours were located on the head and neck region (n = 7), and on the thigh (n = 3). All presented were adults with a slight male predilection. The median tumour size was 10 mm (range: 4-25). Microscopically, lesions displayed features of poroma with nodules of monotonous basophilic cells associated with a second population of larger eosinophilic cells. In all cases, ducts and scattered sebocytes were identified. Infundibular cysts were present in 10 cases. In two cases high mitotic activity was noted, and in three cases cytologic atypia and areas of necrosis were identified. Whole transcriptome RNA sequencing demonstrated in-frame fusion transcripts involving RNF13::PAK2 (n = 4), EPHB3::PAK2 (n = 2), DLG1::PAK2 (n = 2), LRIG1::PAK2 (n = 1), ATP1B3::PAK2 (n = 1), TM9SF4::PAK2 (n = 1), and CTNNA1::PAK2 (n = 1). Moreover, fluorescence in situ hybridisation (FISH) analysis revealed PAK2 rearrangement in an additional case. No YAP1::MAML2 or YAP1::NUTM1 fusion was detected. Recurrent fusions involving the PAK2 gene in all analysed poroma with folliculo-sebaceous differentiation in this study confirms that this neoplasm represents a separate tumour entity distinct from YAP1::MAML2 or YAP1::NUTM1 rearranged poromas.

TRPS1 and GATA3 Expression in Invasive Breast Carcinoma With Apocrine Differentiation.

The recently identified immunohistochemical marker TRPS1 is highly sensitive and specific for invasive breast carcinoma, especially triple-negative breast carcinoma. However, TRPS1 expression in special morphologic subtypes of breast cancer is unclear. To investigate the expression of TRPS1 in invasive breast cancer with apocrine differentiation, in comparison to the expression of GATA3. A total of 52 invasive breast carcinomas with apocrine differentiation, comprising 41 triple-negative breast carcinomas and 11 estrogen receptor (ER) and progesterone receptor (PR)-negative, human epidermal growth factor receptor 2 (HER2)-positive cases, along with 11 triple-negative breast carcinomas without apocrine differentiation, were evaluated for TRPS1 and GATA3 expression by immunohistochemistry. All tumors were diffusely positive (>90%) for androgen receptor (AR). Triple-negative breast carcinoma with apocrine differentiation had positive TRPS1 expression in 12% of cases (5 of 41), whereas GATA3 was positive in all cases. Similarly, HER2+/ER- invasive breast carcinoma with apocrine differentiation showed positive TRPS1 in 18% of cases (2 of 11), whereas GATA3 was positive in all cases. In contrast, triple-negative breast carcinoma with strong AR expression but without apocrine differentiation showed both TRPS1 and GATA3 expression in 100% (11 of 11) of cases. Most ER-/PR-/AR+ invasive breast carcinomas with apocrine differentiation are TRPS1 negative and GATA3 positive, regardless of HER2 status. Therefore, TRPS1 negativity does not exclude breast origin in tumors with apocrine differentiation. A panel of TRPS1 and GATA3 immunostains can be helpful when the tissue origin of such tumors is clinically relevant.

Apocrine Papillary Hidrocystoma With Mucinous Metaplasia (Goblet Cell Type): A Case Report and Review of the Literature.

Mucinous metaplasia (goblet cell type) is exceptionally rare in the skin. This is the second case of apocrine papillary hidrocystoma with mucinous metaplasia (goblet cell type) and a review of the literature exploring the significance and frequency of mucinous metaplasia with goblet cells in nongenital skin. The patient is an elderly man who presented with a blue-pigmented nodule on the scalp that was clinically suggestive of an atypical nevus. Histologically, the lesion was composed of a simple cyst of cuboidal cells with decapitation secretion and mucinous metaplasia with goblet cells. Papillary formation was identified in the cysts. Most cases of cutaneous mucinous metaplasia have been reported on genital skin, usually after chronic inflammation of the area. This type of mucinous metaplasia is categorized as benign mucinous metaplasia of the genitalia (BMM) and is believed to be unrelated to apocrine glands owing to the different histologic features and absence of apocrine differentiation by immunohistochemistry. Mucinous metaplasia (goblet cell type) has been previously reported in benign adnexal tumors (eccrine acrospiroma/hidroadenoma, mixed tumor, and syringocystadenoma papilliferum) and in malignant tumors (apocrine hidradenocarcinoma and squamous cell carcinoma). To date, mucinous metaplasia has not been identified in the histologically normal apocrine glands.

Abstract P4-09-04: Correlation between histology and molecular subtypes in triple negative breast cancer

Abstract Correlation between histology and molecular subtypes in triple negative breast cancer Authors: Tabata Alves Domingos, MD; 1* Roberto Bonfim Pimenta Peixoto, MD; 1* Ashka Patel, BS1,2; Krishan Taneja, PhD; 1 Wendy Y. Chen, MD, MPH; 4,5,6 Elizabeth A. Mittendorf, MD, PhD; 5,6,7 Alexa Zimbalist, MS; 3 Elizabeth M. Cespedes Feliciano, ScD SM; 3 Deborah A. Dillon, MD 1,2 *equal contribution Author Affiliations 1. Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115 2. Breast Oncology, Dana-Farber Brigham Cancer Center, Boston, MA 02215 3. Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612 4. Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA 02115 5. Department of Medical Oncology Dana Farber Cancer Institute, Boston, MA 02215 6. Harvard Medical School, Boston, MA 02215 7. Division of Breast Surgery, Brigham and Women’s Hospital, Boston, MA 02215 Background Recently defined molecular subtypes of triple negative breast cancer (TNBC) show distinct clinical outcomes and suggest new therapeutic targets but have not been integrated into current pathologic classification systems. Here, we describe the histopathologic features of TNBC according to four molecular subtypes: basal-like immune activated (BLIA), basal-like immune suppressed (BLIS), luminal androgen receptor (LAR) and mesenchymal (MES), classified using the NanoString BC360 gene expression assay. Methods Stage II and III invasive breast cancers were identified in the Kaiser Permanente (KP) clinical pathology archives (2005-2015) and triple negative status was determined from the KP Northern California Cancer Registry data on immunohistochemistry. Selected slides were reviewed by two pathologists who recorded key histopathologic features [histologic subtype, presence of apocrine, metaplastic or micropapillary features, nuclear grade, mitotic score, and Tumor Infiltrating Lymphocytes (TILs)] and marked the best tumor areas for molecular analysis. TILs were evaluated according to the guidelines of the International TILs Working Group. Cases were macrodissected and evaluated using the NanoString BC360 gene expression assay. Histologic features were then summarized according to molecular subtype. Results Of 72 TNBCs, 60 were classified as Basal-like (83.3%), 7 as HER2-enriched (9.7%) and 5 as Luminal A (6.9%). 41 cases were classified as BLIA (56.9%), 14 as BLIS (19.4%), 13 as LAR (18.0%) and 4 as MES (5.5%). Both BLIA and BLIS tumors showed uniformly high nuclear grade and high mitotic score but differed significantly in TILs (BLIA average 32% vs BLIS average 9%; p value&amp;lt; 0.001, t-test for mean difference in TILs). The majority of LAR cases (69%) showed apocrine differentiation, not present in any other molecular subtype (p value&amp;lt; 0.001, chi-square test for presence of apocrine differentiation). LAR cases showed high nuclear grade but a lower average mitotic score (average score of 2) compared with the basal-like subtypes. TILs in LAR tumors were intermediate (17%) between BLIA and BLIS tumors. Of the 4 MES cases, all showed high nuclear grade. TILs in the MES cases were also intermediate (14%) between BLIA and BLIS tumors. Other histologic features, including lobular subtype, metaplastic and micropapillary features were not associated with specific triple negative molecular subtypes. Conclusion TILs are high in the BLIA molecular subtype (average 32%), low in the BLIS subtype (average 9%) and intermediate in LAR (average 17%) and MES (average 14%) subtypes. Apocrine features, if present in a TNBC, are a strong predictor of LAR molecular subtype. The inclusion of TILs and apocrine features (both easily derived from H&amp;E slides) in routine pathology reporting could improve the classification of TNBC and aid in the identification of patients more likely to respond to specific therapies for the BLIA, BLIS and LAR subtypes, especially in resource-limited settings. Citation Format: Tabata Alves Domingos, Roberto Bonfim Pimenta Peixoto, Ashka Patel, Krishan Taneja, Wendy Y. Chen, Elizabeth A. Mittendorf, Alexa Zimbalist, Elizabeth M. Cespedes Feliciano, Deborah A. Dillon. Correlation between histology and molecular subtypes in triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-09-04.