Paget's disease of the nipple in a Her2-positive breast cancer xenograft model.

PURPOSE: Paget's disease (PD) of the breast is an uncommon disease of the nipple usually accompanied by an underlying carcinoma, often HER2 + , and accounting for 0.5-5% of all breast cancer. To date, histogenesis of PD of the breast remains controversial, as two theories-transformation and epidermotropic-have been proposed to explain this disease. Currently, animal models recapitulating PD of the nipple have not been described. METHODS: HER2-enriched DT13 breast cancer cells were injected into the mammary fat pad of NOD scid gamma null (NSG) female mice. Immunohistochemical staining and pathological studies were performed on tumor samples, and diagnosis of PD of the nipple was confirmed by expression of proteins characteristic of Paget cells (epidermal growth factor 2 (HER2), androgen receptor (AR), cytokeratin 7 (CK7), cytokeratin 8/18 (CK8/18), and mucin 1 (MUC1)). In addition, DT13 cells grown in 2D culture and in soft agar assays were sensitive to in vitro treatment with pharmacological inhibitors targeting Her2, adenylyl cyclase, mTOR, and PI3K signaling pathways. RESULTS: Mice developed tumors and nipple lesions that were detected exclusively on the tumor-bearing mammary fat pad. Tumor cells were positive for proteins characteristic of Paget cells. In vitro, DT13 cells were sensitive to inhibition of Her2, adenylyl cyclase, mTOR, and PI3K signaling pathways. CONCLUSIONS: Our results suggest that injection of HER2 + DT13 cells into the mammary fat pad of NSG mice recapitulates critical aspects of the pathophysiology of PD of the nipple, supporting the epidermotropic theory as the more likely to explain the histogenesis of this disease.

Recurrent EML4-NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy.

Infantile fibrosarcoma and congenital mesoblastic nephroma are tumors of infancy traditionally associated with the ETV6-NTRK3 gene fusion. However, a number of case reports have identified variant fusions in these tumors. In order to assess the frequency of variant NTRK3 fusions, and in particular whether the recently identified EML4-NTRK3 fusion is recurrent, 63 archival cases of infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analog secretory carcinoma and secretory breast carcinoma (tumor types that are known to carry recurrent ETV6-NTRK3 fusions) were tested with NTRK3 break-apart FISH, EML4-NTRK3 dual fusion FISH, and targeted RNA sequencing. The EML4-NTRK3 fusion was identified in two cases of infantile fibrosarcoma (one of which was previously described), and in one case of congenital mesoblastic nephroma, demonstrating that the EML4-NTRK3 fusion is a recurrent genetic event in these related tumors. The growing spectrum of gene fusions associated with infantile fibrosarcoma and congenital mesoblastic nephroma along with the recent availability of targeted therapies directed toward inhibition of NTRK signaling argue for alternate testing strategies beyond ETV6 break-apart FISH. The use of either NTRK3 FISH or next-generation sequencing will expand the number of cases in which an oncogenic fusion is identified and facilitate optimal diagnosis and treatment for patients.

Diagnostic pitfalls of infarcted Warthin tumor in frozen section evaluation.

Warthin tumor (WT) is the second most common benign salivary gland neoplasm and has characteristic cytologic and histologic findings. Fine-needle aspiration is a common and useful preoperative diagnostic technique, which sometimes leads to ischemic injury resulting in the infarction of these lesions. Infarcted WT may demonstrate variable gross and histologic alterations that may render the diagnosis challenging, particularly during intraoperative frozen section evaluation. In this study, we collected 11 resection specimens from 9 patients with infarcted WT. Seven patients were men and 2 were women, ranging from 49 to 85 years (mean, 69). All the patients had fine-needle aspiration before the resection. Macroscopically, the tumors were tan-white and contained soft, yellow, exudative material. The histologic findings were variable and included necrosis, ghosts of papillae, squamous metaplasia, cholesterol clefts, foamy macrophages, multinucleated giant cell reaction, necrotizing granulomas, and fibrosis. Each case predominantly demonstrated 1 or 2 of these histomorphologic features. In the permanent sections, additional sampling revealed foci of residual viable WT in 8 cases. Three cases were completely infarcted; however, they all had ghost-like papillae in which the architecture of WT was evident. Infarcted WT may present a diagnostic challenge during intraoperative frozen section evaluation. Associated morphologic alterations may preclude a definitive diagnosis of WT and may mimic malignancy. Awareness of the gross and microscopic features associated with infarcted WT is important, particularly for accurate frozen section evaluation of these salivary gland tumors.

Searching for mammary analogue [corrected] secretory carcinoma of salivary gland among its mimics.

Mammary analog secretory carcinoma of salivary gland is a recently described entity with unique morphologic, clinical, and genetic characteristics, including the characteristic t(12;15)(p13;q25) with ETV6-NTRK3 translocation found in secretory carcinomas of the breast. Before their initial description, these salivary gland tumors were generally diagnosed as acinic cell carcinoma or adenocarcinoma. For the purpose of this study, all cases of salivary gland acinic cell carcinoma, cribriform cystadenocarcinoma, and adenocarcinoma, not otherwise specified (NOS), diagnosed over a 10-year period were retrieved from our surgical pathology files. There were a total of 11 cases diagnosed as acinic cell carcinoma, 10 cases of adenocarcinoma, NOS, and 6 cases of cribriform cystadenocarcinoma. All slides were reviewed by two pathologists (AP, CGF) and tumors that show morphologic features of mammary analog secretory carcinoma according to the recent literature were selected. This process narrowed down the initial number to six cases originally diagnosed as acinic cell carcinoma, three cases originally diagnosed as adenocarcinoma, NOS, and one case originally diagnosed as cribriform cystadenocarcinoma. The 10 cases were subjected to immunohistochemistry for S-100, mammaglobin, and ANO1, as well as fluorescence in situ hybridization analysis for t(12;15)(p13;q25) with ETV6-NTRK3 fusion rearrangement. The ETV6-NTRK3 gene rearrangement was detected in three tumors. These three tumors, initially diagnosed as acinic cell carcinomas, stained positive for S-100 and mammaglobin, and negative for ANO1 by immunohistochemistry. Two of the three patients were male (2/3). In summary, mammary analog secretory carcinoma is a newly described diagnostic entity that should be in the differential diagnosis of salivary gland tumors that morphologically mimic other neoplasms, mainly acinic cell carcinomas. They differ from conventional acinic cell tumors immunohistochemically and molecularly. Positivity for mammaglobin and S-100, and negativity for ANO1 are useful screening tools before confirmatory molecular studies.

Transitional cell-type papillary carcinoma of the lacrimal sac manifesting as a medial canthal skin lesion.

A 61-year-old man presented with a 2.5 cm fungating skin lesion above the right medial canthus, accompanied by fluctuance and subtle inferotemporal globe displacement. The tumor had erupted 2 months previously and grown rapidly. Computed tomography (CT) revealed a 4.2 × 2.8 × 2.1 cm exophytic mass of the right orbit, superimposed on chronic dacryocystitis. Incisional biopsy disclosed faulty epithelial maturation sequence with possible basement membrane invasion. The patient underwent wide excision with medial maxillectomy, inferior turbinectomy, ethmoidectomy, and partial rhinectomy. The orbital floor was then reconstructed; a paramedian forehead flap and myocutaneous cheek advancement flap were used to fill cutaneous defects. All surgical margins were negative on both frozen and permanent sections. Definitive histopathology was consistent with transitional cell type papillary carcinoma of the lacrimal sac. Adjuvant radiotherapy was recommended, but the patient has declined further treatment. He remains recurrence-free at one year.

Trichorhinophalangeal Syndrome Type 1 Immunohistochemical Expression in Carcinomas of Gynecologic Origin.

Trichorhinophalangeal syndrome type 1 (TRPS1) is a new reportedly sensitive and specific immunohistochemical marker for carcinomas of breast origin, including triple-negative (estrogen receptor, progesterone receptor, and HER2) tumors. In our practice, we have observed a subset of cases of nonmammary carcinomas that are positive for TRPS1, with higher frequency in cytology effusion samples with metastatic gynecologic malignancies. This study aimed to evaluate the expression of TRPS1 in a large tissue cohort of Müllerian carcinomas. We retrospectively retrieved 105 cases of formalin-fixed paraffin-embedded gynecologic tumors from our surgical pathology archives. Cases corresponded to tumors of tubo-ovarian (17 high-grade serous carcinomas, 3 low-grade serous carcinomas, 2 clear cell carcinomas, and 8 endometrioid adenocarcinomas), endometrial (25 endometrioid adenocarcinomas, 8 serous carcinomas, 6 clear cell carcinomas, 12 carcinosarcomas, 1 dedifferentiated carcinoma, and 1 mesonephric-like adenocarcinoma), cervical (6 human papillomavirus [HPV]-associated squamous cell carcinomas [SCCs], 11 HPV-associated endocervical adenocarcinomas, and 2 HPV-independent gastric-type endocervical adenocarcinomas), and vulvar (2 HPV-independent SCCs and 1 HPV-associated SCC) origins. Immunohistochemistry for TRPS1 was performed in whole tissue sections and assessed for positivity (≥5% of nuclear labeling), distribution (focal: 5% to 49%, diffuse: 50% to 100%), and intensity (1+, 2+, 3+) in tumor cells. Positive TRPS1 staining was observed in 51.4% (54/105) of cases. Most tumors (64.8%) demonstrated diffuse labeling, while focal in 35.2%. Among positive cases, the intensity was predominantly 1+ (57.4%), followed by 2+ (33.3%) and 3+ (9.2%). Tumors with a high percentage of positivity overall consisted of tubo-ovarian (70%) and endometrial carcinomas (58.4%). TRPS1 immunostain is often expressed in gynecologic carcinomas. Awareness of this phenomenon is crucial when evaluating challenging cases in which the differential diagnosis includes a malignancy of breast origin, to avoid misclassification of the primary site.

Don't SUMP it! Utility of PLAG1 immunocytochemistry in basaloid SUMP subcategory.

BACKGROUND: Basaloid salivary gland neoplasm of uncertain malignant potential (B-SUMP) is an indeterminate diagnostic subcategory, with pleomorphic adenoma (PA) representing the most common benign neoplasm. Pleomorphic adenoma gene 1 (PLAG1) staining is frequently seen in PAs and could aid in distinguishing them from other basaloid neoplasms. The authors evaluated the utility of PLAG1 immunocytochemistry (ICC) in differentiating PAs from other basaloid neoplasms in smears and liquid-based cytology (LBC) specimens. METHODS: In total, 45 B-SUMP cytology aspirates and corresponding surgical excision specimens were identified. PLAG1 immunostaining was performed in all aspirates and surgical excision specimens and was scored as positive (strong/diffuse), equivocal (focal/weak), or negative. RESULTS: PLAG1 ICC was performed directly on 38 smears and seven LBC specimens. PLAG1 was positive in 29 of 45 cases (64%), whereas six of 45 (13%) were equivocal, and 10 of 45 (22%) were negative. PLAG1-positive aspirates included 26 (90%) PAs, two (7%) basal cell adenomas (BCAs), and one (3%) carcinoma ex-PA. PLAG1-equivocal aspirates included four (67%) PAs and two (33%) BCAs, whereas negative aspirates included five (50%) BCAs, four (40%) adenoid cystic carcinomas, and one (10%) metastatic adenosquamous carcinoma. The sensitivity, specificity, positive, and negative predictive values were 87%, 86%, 93%, and 75%, respectively. Diagnostic accuracy was 87%. CONCLUSIONS: PLAG1 ICC is useful when positive (strong/diffuse) and can be reliably performed on smears and LBC specimens. PLAG1 was positive in most PAs and in a small subset of BCAs. Therefore, in the absence of atypical cytologic features, PLAG1-positive tumors could be diagnosed as benign, with a note favoring PA versus BCA. In contrast, PLAG1-negative/equivocal tumors should remain in the B-SUMP category.

Mesenchymal neoplasms of the tongue: A clinicopathologic study of 93 cases.

Neoplasms of the tongue are relatively common, and the vast majority are epithelial in phenotype. Although uncommon, a diverse and distinctive array of mesenchymal neoplasms arises in this anatomic site. To increase our understanding of these lesions, we reviewed our experience of MNs of the tongue and described their clinicopathologic features. The pathology archives from 2005 to 2021 and the consultation files of one of the authors were queried for all MNs of the tongue. We reviewed the histologic slides and ancillary studies and obtained clinical data from the available medical records. Ninety-three cases were identified, and they form the study cohort - to our knowledge, this is the largest series of mesenchymal neoplasms of the tongue. Forty-eight patients were female, and forty-five were male, with a mean age of 51 years (range: 1-94 years). The tumors included 43 (46.2%) hemangiomas, 14 (15%) granular cell tumors, 8 (9%) lipomas, 4 (4.3%) schwannomas, 4 (4.3%) solitary fibrous tumors - all with low risk of progression based on risk stratification criteria, 2 (2.2%) lymphangiomas, 3 (3.2%) Kaposi sarcomas, 2 (2.2%) chondromas, 2 (2.2%) myofibromas, 1 (1.1%) solitary circumscribed neuroma, 1 (1.1%) perineurioma, 1 (1.1%) neurofibroma, 1 (1.1%) ectomesenchymal chondromyxoid tumor, 1 (1.1%) atypical glomus tumor with a NOTCH2 rearrangement and TLL2 mutation, 1 (1.1%) spindle cell rhabdomyosarcoma, 1 (1.1%) pleomorphic fibroblastic sarcoma, 1 (1.1%) malignant rhabdoid tumor, 1 (1.1%) leiomyosarcoma, 1 (1.1%) angiosarcoma, and 1 (1.1%) alveolar soft part sarcoma. Most of the patients underwent surgical excision, and 1 patient (with hemangioma) underwent embolization. On follow-up, the patient with spindle cell rhabdomyosarcoma developed postoperative numbness at the surgical site and was disease-free through 17 months of follow-up. The patient with leiomyosarcoma declined adjuvant radiation and developed metastasis to the lung at 22 months. The patient with alveolar soft part sarcoma had metastases to the lung at the time of diagnosis and received adjuvant chemotherapy. The remaining patients had no local or distant recurrence. MNs of the tongue are usually benign and characterized by either endothelial, adipocytic, or schwannian differentiation. The mainstay of treatment is surgical excision with the extent of excision determined by tumor type. Adjuvant therapy is reserved for high-grade sarcomas.

Utility of the Milan System for Reporting Salivary Gland Cytopathology in fine needle aspiration cytology of minor salivary gland lesions.

INTRODUCTION: Salivary gland lesions are routinely evaluated by fine-needle aspiration cytology (FNAC) preoperatively. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has standardized salivary gland FNAC reporting. Its application in major salivary glands (MSGs) has been well-established; however, its utility in minor salivary glands (MiSGs) is not well-known. We studied the utility of MSRSGC in MiSG FNAC. MATERIALS AND METHODS: A retrospective search of MiSG FNACs from 2 academic institutions (2006-2023) was performed. FNACs were classified using the MSRSGC. Histologic data were reviewed and recorded. The risk of malignancy (ROM), risk of neoplasia (RON), diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: The series included 43 MiSG FNAC (24 males and 18 females), with a mean age of 55 years (range 10-92). Aspirated sites included the following: palate, buccal space, floor of mouth, lip, tongue, and maxillary sinus. FNACs were classified as nondiagnostic (1), nonneoplastic (3), atypia of undetermined significance (6), benign neoplasm (9), salivary gland neoplasm of uncertain malignant potential (15), suspicious for malignancy, (2) and malignant (7). The risk of neoplasia and risk of malignancy were 87% and 39%. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 100%, respectively. CONCLUSIONS: Milan System for Reporting Salivary Gland Cytopathology offers valuable information for stratifying MiSG lesions. However, the distribution and the range of diagnostic entities encountered differ somewhat from those in MSGs. For instance, mucinous cyst contents may warrant unique consideration in MiSG; while an atypical classification is recommended in MSGs, the high prevalence of mucoceles in MiSG may tilt this group toward benignity.

Paget's disease of the nipple.

Paget's disease of the breast is a disorder of the nipple-areola complex that, while rare, is often associated with an underlying carcinoma. It is characterized by eczematoid changes of the nipple. Two theories have been proposed to explain the pathogenesis of Paget's disease. The Epidermotropic, which is the most accepted theory, suggests that Paget's cells originate from ductal cancer cells that had migrated from the underlying breast parenchyma. It is supported by the predominance of breast cancer markers found in Paget's disease. This article provides an overview of Paget's disease of the breast with special attention to immunohistochemistry and raises the question of new therapeutic approaches.

The use of neoadjuvant platinum-based chemotherapy in locally advanced breast cancer that is triple negative: retrospective analysis of 144 patients.

Triple-negative breast cancers comprise about 20 % of breast cancers. They have poor prognosis and have no standard therapy. The aim of this study was to evaluate pathologic complete response (pCR), progression-free survival (PFS), and overall survival (OS) in patients with TNBC treated with neoadjuvant platinum-based chemotherapy. This is a retrospective study of one hundred and forty-four women with TNBC treated with neoadjuvant platinum-containing chemotherapy for locally advanced breast cancer at the University of Miami between January 1, 1999, and January 1, 2011. The medical record was reviewed to obtain data on clinical characteristics, including ethnicity, race, age, clinical stage, treatment regimen, and vital status. This study was approved by the University of Miami IRB. All patients had locally advanced breast cancer with at least one of the following features at presentation: T3, T4, N2, and N3. The mean tumor size by palpation was 9.4 cm. The clinical T-stage at presentation was 1.4 % T1, 8.3 % T2, 52.8 % T3, and 37.5 % T4 (19.4 % T4d). The nodal status by physical exam at presentation was 23 % N0, 37.5 % N1, 34 % N2, and 5.5 % N3. pCR in breast and axilla was seen in 31 %. PFS and OS were 55 and 59 %, respectively, at 7 years. Cisplatin offered a survival advantage over carboplatin in both PFS (P = 0.007) and OS (P = 0.018). Node positivity was the most important predictor of survival. Cisplatin/docetaxel neoadjuvant therapy was well tolerated and an effective therapy in locally advanced TNB.

p16INKa immunocytochemistry in fine-needle aspiration cytology smears of metastatic head and neck squamous cell carcinoma.

OBJECTIVES: Patients with head and neck squamous cell carcinoma (HNSCC) may initially present with neck metastases diagnosed by fine-needle aspiration (FNA). In these patients, it is critical to locate the primary site so that targeted therapy can be administered. Nearly a quarter of HNSCC are associated with human papillomavirus (HPV) infection. The great majority of HPV-related primaries originate in the oropharynx. p16INKa (p16) functions as a surrogate marker of HPV infection. We sought to determine if expression of p16 by immunocytochemistry (ICC) in neck metastases could assist in localizing the primary site to the oropharynx. STUDY DESIGN: Diagnostic FNA cytology smears of neck metastases from 90 patients with biopsy-proven primary HNSCC were reviewed. Papanicolaou-stained slides were directly subjected to ICC, using p16 antibody. RESULTS: Twenty-seven (30%) tumors expressed p16 by ICC; 74% of these p16-positive tumors were metastases from oropharynx. There was a significantly higher proportion of p16 expression in patients with primary oropharyngeal carcinoma (47%) versus those whose primary tumor was non-oropharyngeal (15%; p = 0.0013). CONCLUSIONS: p16 expression in FNA cytology smears of metastatic HNSCC is a useful indicator of oropharyngeal origin and can be used to help localize the primary site in cases where this is not clinically evident.

TRPS1 immunohistochemical expression in salivary gland tumors: A pilot study.

OBJECTIVES: TRPS1 is a new, sensitive marker for breast carcinoma (BC). Salivary glands and breasts are both exocrine glands; thus, their tumors may share similar morphology and immunophenotype. Among salivary gland-type BC, TRPS1 is reported to be positive in secretory carcinomas (SCs) but negative in acinic cell carcinomas (AciCCs) and most adenoid cystic carcinomas (AdCCs). A subset of salivary duct carcinomas (SDCs) is positive for TRPS1. Herein, we investigate TRPS1 immunohistochemical expression in salivary gland tumors (SGTs). METHODS: A retrospective search yielded 110 SGTs (97 primary and 13 metastatic). TRPS1 immunohistochemistry was scored as negative, low positive, intermediate positive, or strongly positive. RESULTS: TRPS1 was expressed in 78% (14/18) of pleomorphic adenoma (PA) cases but negative/low positive in all Warthin tumors (6/6 [100%]). In basal cell adenoma (BCA), TRPS1 expression was intermediate to strong (13/14 [92%]) in the stromal cells, whereas ductal or basal cells showed low expression. TRPS1 expression varied in malignant SGTs, with intermediate to strong staining in 100% (15/15) of AdCCs, 100% (5/5) of basal cell adenocarcinoma, 100% (3/3) of intraductal carcinoma, 89% (8/9) of polymorphous adenocarcinoma, and 89% (7/8) of SDCs; negative/low positive expression was observed in 100% (3/3) of SCs, 89% (8/9) of AciCCs, and 50% (3/3) of mucoepidermoid carcinomas. In addition, strong and intermediate TRPS1 expression was observed in metastatic SGT to the lungs, lymph nodes, and soft tissue. CONCLUSIONS: Overall, TRPS1 is strongly expressed in PA as well as malignant and metastatic SGT. In addition, TRPS1 is positive in stromal cells of BCA but negative or low positive in ductal and basal cells.

Utility of high-risk HPV RNA chromogenic in situ hybridization in cytology smears and liquid-based preparations from metastatic head and neck squamous cell carcinoma.

BACKGROUND: High-risk human papillomavirus (HR-HPV) status is critical for the diagnosis, prognosis, and treatment of patients with oropharyngeal squamous cell carcinoma (OPSCC). Patients often present with enlarged cervical nodes, and fine-needle aspiration cytology (FNAC) is frequently the initial diagnostic procedure. Although p16 is the most widely used surrogate marker, problems with interpretation can limit its utility in FNAC. HR-HPV RNA in situ hybridization (ISH) has emerged as a specific way to assess HPV status on cell block preparations of cervical nodes. The authors evaluated the utility of HR-HPV ISH in conventional smears and liquid-based cytology (LBC) preparations of metastatic head and neck squamous cell carcinoma (SCC). METHODS: Thirty-one aspirates of proven, HPV-related SCC (confirmed by p16 and/or HR-HPV ISH in corresponding surgical specimens) were selected. Ten aspirates of HPV-negative SCC were also retrieved. HR-HPV ISH was performed on 27 smears and 14 LBC preparations. All results were scored as positive, equivocal, or negative. RESULTS: Eighty-four percent of metastatic, HPV-related SCCs were positive for HR-HPV RNA ISH, with high number of signals (n = 19) and low number of signals (n = 7), whereas five HPV-related SCCs were equivocal. All metastatic, HPV-negative SCCs were negative for HR-HPV ISH. CONCLUSIONS: HR-HPV ISH can be reliably performed on smears or LBC preparations, particularly when cell blocks are unavailable or paucicellular. Results were easy to interpret when high numbers of signals were present but were challenging in aspirates with low or rare number of signals. The current study suggests that HR-HPV ISH could be used as the initial testing modality for determining HPV status in FNAC specimens of metastatic SCC.

Utility of TRPS1 in Malignant Effusion Cytology.

INTRODUCTION: Identifying metastatic breast carcinoma (mBC) in malignant effusion cytology (MEC) specimens is critical, as this will determine the patient's prognosis and therapeutic management. Overlapping cytomorphologic features of breast carcinoma (BC) with other neoplastic entities makes the use of sensitive and specific markers highly desirable. Recent studies have reported trichorhinophalangeal syndrome type 1 (TRPS1) as a sensitive and specific marker for primary BC and mBC. We aimed to investigate TRPS1 expression in MEC of mBC and its most common diagnostic mimickers. MATERIALS AND METHODS: A retrospective search from the pathology archives identified 82 MEC. TRPS1 expression in mBC was analyzed, and the results were compared to those in metastatic carcinoma of Müllerian origin (mMC) and metastatic pulmonary adenocarcinoma (mPAC). TRPS1 immunoperoxidase was performed on cytospin or cell block preparations, and p < 0.05 was considered significant. RESULTS: Nuclear expression for TRPS1 was evaluated and scored as positive (≥1% of tumor cells) or negative. Nuclear TRPS1 expression was seen in 100% (30/30) mBC, 72% (18/25) mMC, and 7% (2/27) mPAC. This resulted in sensitivity, specificity, positive predictive value, and negative predictive values of 100%, 61%, 60%, and 100%, respectively. CONCLUSION: TRPS1 is a sensitive marker for mBC and can be reliably performed on cytology specimens. TRPS1 expression was also identified in a significant proportion of mMC, creating a potential diagnostic pitfall. Therefore, caution should be exercised when evaluating MEC of mBC with TRPS1. Consequently, a combination of immunoperoxidase panels should be employed in this setting.

Probability of malignancy and molecular alterations as determined by ThyroSeq v3 genomic classifier in Bethesda Category IV.

BACKGROUND: ThyroSeq molecular testing assesses the probability of malignancy (POM) in thyroid fine-needle aspiration cytology (FNAC) with indeterminate cytology. The aim was to investigate whether Bethesda category IV (BIV) subcategories are associated with specific molecular alterations, molecular-derived risk of malignancy (MDROM), and risk of malignancy (ROM). METHODS: FNAC slides, associated ThyroSeq, version 3, Genomic Classifier results, and surgical follow-up were retrieved for BIV nodules. Nodules were subcategorized as follicular neoplasm (FN) with or without cytologic atypia or oncocytic follicular neoplasm (OFN). The MDROM, ROM, and frequency of molecular alterations in FN and OFN were analyzed. p < .05 was considered significant. RESULTS: A total of 92 FNAC were identified and subcategorized into 46 FN (15 with and 31 without cytologic atypia) and 46 OFN. The benign call rate and the positive call rate were 49% and 51%, respectively. The MDROM in BIV was 34.3%, trending lower in OFN than in FN. RAS mutations were significantly more frequent in FN when compared to OFN (p = .02). Chromosomal copy number alterations were more often present in OFN than in FN (p < .01). On histologic follow-up, ROM in OFN was trending lower than in FN (p = .1). The most common diagnosis in OFN was oncocytic adenoma, whereas follicular variant papillary thyroid carcinoma was most common in FN. CONCLUSIONS: The MDROM and ROM were trending lower in OFN compared with FN, and the molecular alterations differed between OFN and FN subcategories.

Axillary lymph node "bubbly" calcifications and body tattoo: A case series and proposed algorithm to minimize lymph node biopsies.

The presence of mammographically evident hyperdense foci within axillary lymph nodes elicits concern for calcium deposits, which in turn have a wide differential diagnosis including both benign and malignant entities. Tissue sampling, most commonly by way of image-guided core needle biopsy, is needed in many cases when a definite etiology cannot be clinically established. In this case series we present history, imaging findings, and pathology results (or long term follow-up stability as biopsy surrogate) of several women with body tattoos who at mammography were noted to have a characteristic pattern of "bubbly" pseudo-calcifications within axillary lymph nodes, and absence of other mammographic, sonographic and clinical abnormalities.

Application of the Milan System for Reporting Salivary Gland Cytopathology: A Single Institutional Experience of 354 Cases with Cytologic-Histologic Correlation.

BACKGROUND: Evaluation of salivary gland lesions is routinely done preoperatively by fine-needle aspiration cytology (FNAC). The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), with diagnostic categories I-VI, has been recommended to standardize the reporting of salivary gland lesions by FNAC. We aimed to reclassify archival salivary gland FNAC samples using MSRSGC, correlate the samples with surgical resections, and calculate the risk of malignancy (ROM) for each category. METHODS: A total of 354 salivary gland FNAC samples (2013-2018) were reviewed. All FNAC results were retrospectively classified according to the MSRSGC. All cases had surgical follow-up. Histology was used to calculate the ROM, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy. RESULTS: The 354 aspirates were classified as: nondiagnostic (ND) 17.0% (60), non-neoplastic (NN) 1.4% (5), atypia of undetermined significance (AUS) 11.0% (39), benign neoplasm (BN) 49.4% (175), salivary gland neoplasms of unknown malignant potential (SUMP) 10.7% (38), suspicious for malignancy (SM) 3.4% (12), and malignant (M) 7.1% (25). The ROM was as follows: ND 22%, NN 20%, AUS 15%, BN 2%, SUMP 53%, SM 75%, and M 96%. The diagnostic accuracy for separating benign versus malignant neoplasms was 96%. Cytologic-histologic correlation yielded a false-negative rate of 2.7%, false-positive rate of 10.5%, PPV of 89%, NPV of 97%, sensitivity of 87%, and specificity of 98%. CONCLUSION: MSRSGC helps standardize cytology reports, provides useful information for appropriate clinical management, and ensures the best care of patients with salivary gland lesions.

Risk of malignancy associated with the diagnostic categories proposed by the Papanicolaou Society of Cytopathology for pancreaticobiliary specimens: An institutional experience.

BACKGROUND: The guidelines published by the Papanicolaou Society of Cytopathology (PSC) intend to unify the reporting language in pancreaticobiliary specimens and improve communication between cytopathologists and clinicians. The six categories in the system will determine the best management for patients. However, there is limited evidence regarding the risk of malignancy (ROM) associated with each category. METHODS: A retrospective search was performed for pancreaticobiliary fine-needle aspiration (FNA) reports with corresponding surgical follow-up. Cases were reclassified according to the PSC. The ROM, sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each category. RESULTS: A total of 297 cases were identified and reclassified as: 30 nondiagnostic (category I), 45 negative for malignancy (II), 20 atypical (III), 42 neoplastic: other (IVB), 19 suspicious for malignancy (V), and 141 malignant (VI). The absolute ROM was 10% for category I, 8.9% for category II, 60% for category III, 4.8% for category IV when the neoplasms were not characterized as malignant, and 100% when categorized as malignant; 100% for category V, and 95.7% for category VI. Sensitivity, specificity, positive predictive value, and negative predictive value for neoplasia and malignancy, including categories IV to VI, were 96.6%, 88.4%, 97.5%, and 84.4%, respectively. CONCLUSIONS: The categories developed by the PSC stratify the ROM. Aspirates designated as categories V and VI had the highest ROM. Our rate of atypical category complies with the recommended rate of <10%. This scheme provides valuable information to clinicians treating patients with pancreatic lesions.

Utility of NR4A3 on FNA cytology smears and liquid-based preparations of salivary gland.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is generally the initial sampling method for salivary gland neoplasms. The cytomorphologic features of acinic cell carcinoma (AciCC) of salivary gland can overlap with other neoplastic and nonneoplastic entities. AciCCs harbor a recurrent t(4;9) rearrangement with upregulation of nuclear receptor subfamily 4 group A member 3 (NR4A3). NR4A3 protein overexpression has been shown to be highly sensitive and specific for the diagnosis of AciCC in histologic specimens and cell block preparations. However, data on NR4A3 immunocytochemistry (ICC) on conventional smears or liquid-based cytology are limited. METHODS: The authors identified 18 FNAC of histologically proven AciCC cases between 2013 and 2019. FNAC samples of diagnostic mimickers were likewise retrieved and included in the study cohort for comparison. The NOR1/NR4A3 mouse monoclonal antibody was applied directly to FNAC slides using a standard ICC technique. RESULTS: The cohort included ethanol-fixed Papanicolaou-stained cytologic smears and liquid-based preparations from 18 AciCC, one secretory carcinoma, four mucoepidermoid carcinomas, four salivary duct carcinomas, five pleomorphic adenomas (PA), five Warthin tumors, five oncocytomas, one oncocytic hyperplasia, and five nonneoplastic salivary gland cases. Strong nuclear staining for NR4A3 was present in all AciCC, weak nuclear staining was present in one PA, and all other non-AciCC were negative (sensitivity, 100%; specificity, 97%). CONCLUSIONS: NR4A3 ICC can be used directly on FNAC conventional smears and liquid-based cytology to reliably distinguish AciCC from its mimickers. This marker may be useful in cases where a cell block preparation is unavailable or inadequate.