Synovial Sarcoma of the Gastrointestinal Tract.

We report the clinicopathologic and immunohistochemical features of 18 cases of confirmed primary synovial sarcoma of the gastrointestinal tract. The neoplasms arose in 10 women and 8 men ranging in age from 23 to 81 years (mean: 50; median: 57.5 years). The tumors for which size was known ranged from 1.8 to 15.0 cm (mean: 5.2; median: 5.1 cm). Microscopically, 14 synovial sarcomas were of the monophasic type, 2 were biphasic, and 2 were poorly differentiated. Immunohistochemical analysis of 4 cases showed strong, diffuse staining for SS18::SSX (4/4 cases). Pancytokeratin and EMA immunohistochemistry were performed on 13 and 9 tumors, respectively, and each showed patchy-to-diffuse staining. By reverse-transcription PCR, 3 cases were positive for the SS18::SSX1, and 2 cases were positive for the SS18::SSX2 gene fusion. Six cases contained an SS18 gene rearrangement by fluorescence in situ hybridization, and next-generation sequencing identified an SS18::SSX2 gene fusion in one case. Clinical follow-up information was available for 9 patients (4 months to 4.6 years; mean, 2.8 y; median: 29 months), and one patient had a recent diagnosis. Three patients died of disease within 41 to 72 months (mean, 56 months) of their diagnosis. Five patients were alive without evidence of disease 4 to 52 months (mean, 17.6 months) after surgery; of whom 1 of the patients received additional chemotherapy treatment after surgery because of recurrence of the disease. A single patient was alive with intraabdominal recurrence 13 months after surgery. We conclude that synovial sarcoma of the gastrointestinal tract is an aggressive tumor, similar to its soft tissue counterpart, with adverse patient outcomes. It is important to distinguish it from morphologically similar gastrointestinal tract lesions that may have different treatment regimens and prognoses.

Common Diagnostic Challenges in Genitourinary Mesenchymal Tumors: A Practical Approach.

Mesenchymal neoplasms within the genitourinary tract include a wide spectrum of tumors, ranging from benign to malignant, and tumors of uncertain malignant potential. Except for stromal tumors of the prostate, which originate from the specific prostatic stroma, these neoplasms generally resemble their counterparts in other body sites. The rarity of these neoplasms and the limitation associated with small biopsy samples present unique diagnostic challenges for pathologists. Accurate diagnosis is paramount, as it significantly influences prognosis and guides management and treatment strategies. This review addresses common diagnostic scenarios, discusses key differential diagnoses, and sheds light on potential diagnostic pitfalls.

Sinonasal Myxoma: A Distinct Entity or a Myxoid Variant of Desmoid Fibromatosis?

Sinonasal myxoma (SNM) is a rare benign mesenchymal tumor that arises in the sinonasal cavity or maxilla and almost exclusively affects young children. Currently, it is considered a specific entity, but its molecular characteristics have not been reported. Lesions diagnosed as SNM and odontogenic myxoma/fibromyxoma were identified from the participating institutions, and the clinicopathologic features were recorded. Immunohistochemistry for ß-catenin was performed in all cases with available tissue. Next-generation sequencing was performed in all cases with SNM. Five patients with SNM were identified, including 3 boys and 2 girls with an age range of 20-36 months (mean: 26 months). The tumors were well defined, centered in the maxillary sinus, surrounded by a rim of woven bone, and composed of a moderately cellular proliferation of spindle cells oriented in intersecting fascicles in a variably myxocollagenous stroma that contained extravasated erythrocytes. Histologically, the tumors resembled myxoid desmoid fibromatosis. Three tested cases showed nuclear expression of ß-catenin. In 3 tumors, next-generation sequencing revealed intragenic deletions of APC exons 5-6, 9 and 15, or 16, respectively, with concurrent loss of the other wild-type copy of APC predicted to result in biallelic inactivation. The deletions were identical to those that occur in desmoid fibromatosis, and copy number analysis raised the possibility that they were germline. In addition, 1 case showed the possible deletion of APC exons 12-14, and another case exhibited a CTNNB1 p. S33C mutation. Ten patients with odontogenic myxoma/fibromyxoma were identified, including 4 women and 6 men (mean age: 42 years). Seven tumors involved the mandible and 3 the maxilla. Histologically, the tumors differed from SNM, and all cases lacked nuclear expression of ß-catenin. These findings suggest that SNM represents a myxoid variant of desmoid fibromatosis that often arises in the maxilla. The APC alterations might be germline, and therefore, genetic testing of the affected patients should be considered.

Nuclear expression of AFF2 C-terminus is a sensitive and specific ancillary marker for DEK::AFF2 carcinoma of the sinonasal tract.

DEK::AFF2 carcinoma of the sinonasal tract is an emerging entity. The tumor is typically characterized by papillary proliferation of non-keratinizing squamous epithelial cells with monotonous cytologic features, which may mimic other sinonasal tumors. The confirmation of this gene fusion has thus far relied solely on next-generation sequencing, fluorescence in situ hybridization (FISH), or reverse transcription polymerase chain reaction (RT-PCR). This current study aimed to validate an immunohistochemical assay for AFF2 C-terminus as an ancillary marker. We first analyzed publicly available RNA sequencing data of sinonasal tumors from the national center for biotechnology information (NCBI) sequence read archive and identified 3 DEK::AFF2 carcinomas out of 28 sinonasal tumors. The gene expression of AFF2 was significantly higher in the fusion-positive cases compared to the wild-type tumors (p < 0.001), while DEK was not. We then optimized an immunohistochemical assay with an anti-AFF2 C-terminus antibody for ancillary diagnosis. Seventeen DEK::AFF2 carcinomas, including 11 cases with predominantly low-grade morphology and one showing glandular differentiation, as well as 78 DEK FISH-negative sinonasal tumors were evaluated by AFF2 immunohistochemistry (IHC). Sixteen of the 17 DEK::AFF2 carcinomas showed nuclear AFF2 expression in ≥30% of tumor cells, including one decalcified case that failed FISH and RT-PCR confirmation. The one case that was negative for AFF2 IHC in the tumor cells also lacked expression in the internal positive control. It was thus considered a failure of the IHC rather than a truly negative case and was excluded from the statistical analysis. All DEK FISH-negative sinonasal tumors were negative for nuclear AFF2 expression. The nuclear expression of AFF2 IHC showed 100% sensitivity and specificity for DEK::AFF2 carcinoma. Accordingly, AFF2 IHC is a highly sensitive and specific ancillary marker that distinguishes DEK-AFF2 carcinoma from the other sinonasal tumors with overlapping morphological features and may be an especially useful alternative for decalcified specimens.

Novel fusion genes in spindle cell rhabdomyosarcoma: The spectrum broadens.

Rhabdomyosarcoma (RMS) encompasses a heterogeneous group of tumors with striated muscle differentiation. RMSs are classified as alveolar, embryonal, spindle cell/sclerosing, and pleomorphic types and molecular analysis of these tumors has identified aberrations that are useful in their further subclassification. Spindle cell rhabdomyosarcoma (SpRMS) is uncommon and has been described with VGLL2 fusions, EWSR1/FUS-TFCP2 rearrangements, and myoD1 mutations-the mutations are associated with significantly different prognoses. In addition, the NCOA2-MEIS1 fusion gene was recently described in two primary intraosseous RMS that contained spindle cell components. Herein, we report three cases of SpRMS harboring different novel fusion genes, one possessing EP300-VGLL3, a second with NCOA2-MEIS1 and CAV1-MET, and the third case had HMGA2-NEGR1 and multiple amplified genes.

Cardiac Myxoma: Review and Update of Contemporary Immunohistochemical Markers and Molecular Pathology.

Cardiac myxoma is an uncommon benign mesenchymal neoplasm of the heart. It usually arises in the left atrium, near the valve of the fossa ovalis, and most frequently affects adults in the third through the sixth decades of life. It is hypothesized to arise from subendothelial vasoformative reserve cells or primitive cells that differentiate along the lines of the endothelium, but this remains speculative. Microscopically, the neoplastic cells are arranged individually, and nests, and are oriented in single or multiple layers around vascular channels. The neoplastic cells are immunoreactive for vimentin, calretinin, S100, nonspecific enolase, factor VIII, CD31, and CD34. The tumor can have diverse clinical presentations depending on its location and extent of disease and is predisposed to embolization. The current treatment is prompt surgical excision.

Follicular neoplasms with nuclear atypia versus other types of atypia: Should follicular neoplasms be stratified according to the presence of nuclear atypia?

BACKGROUND: The third edition of The Bethesda System (TBS) subclassifies the atypia of undetermined significance (AUS) category on the basis of the presence of nuclear atypia (AUS-Nuclear). This approach is supported by studies showing significant differences in the risk of malignancy (ROM) between AUS-Nuclear and those without (AUS-Other). Although aspirates of follicular neoplasms (FNs) are characterized by marked architectural atypia, TBS recognizes the infrequent occurrence of FNs with mild nuclear atypia (FN-Nuclear). Furthermore, limited studies have shown significant differences in ROM between FN-Nuclear and those without (FN-Other). This study explored potential differences in ROM, molecular-derived risk of malignancy (MDROM), and molecular alterations between FN-Nuclear and FN-Other. METHODS: A retrospective database search identified 93 FN aspirates. Cytology slides, molecular reports, and histologic follow-ups were reviewed. Both groups' benign call rate (BCR), positive call rate (PCR), MDROM, and ROM were computed and compared. RESULTS: Eighty-six percent of aspirates (80 of 93) comprised FN-Other, whereas 14% (13 of 93) were FN-Nuclear. The BCR and PCR for FN-Other were 51% and 49%, respectively. In contrast, they were 23% and 77% for FN-Nuclear, respectively. The MDROM significantly differed between FN-Other (30%) and FN-Nuclear (56%) (p < .05). HRAS mutation was the most common molecular alteration in FN-Nuclear, whereas mutations in NRAS/KRAS and copy number alterations were more common in FN-Other. The ROM1/ROM2 in FN-Other and FN-Nuclear were 16%/31% and 54%/88%, respectively. CONCLUSIONS: These results reveal that FN-Nuclear exhibits significantly higher MDROM and ROM than FN-Other, which provides support for a subclassification scheme for FNs based on the presence of nuclear atypia.

Thyroid Fine-Needle Aspiration: The Current and Future Landscape of Cytopathology.

Thyroid cytology is a rapidly evolving field that has seen significant advances in recent years. Its main goal is to accurately diagnose thyroid nodules, differentiate between benign and malignant lesions, and risk stratify nodules when a definitive diagnosis is not possible. The current landscape of thyroid cytology includes the use of fine-needle aspiration for the diagnosis of thyroid nodules with the use of uniform, tiered reporting systems such as the Bethesda System for Reporting Thyroid Cytopathology. In recent years, molecular testing has emerged as a reliable preoperative diagnostic tool that stratifies patients into different risk categories (low, intermediate, or high) with varying probabilities of malignancy and helps guide patient treatment.

Artificial Intelligence Applications in Cytopathology: Current State of the Art.

The practice of cytopathology has been significantly refined in recent years, largely through the creation of consensus rule sets for the diagnosis of particular specimens (Bethesda, Milan, Paris, and so forth). In general, these diagnostic systems have focused on reducing intraobserver variance, removing nebulous/redundant categories, reducing the use of "atypical" diagnoses, and promoting the use of quantitative scoring systems while providing a uniform language to communicate these results. Computational pathology is a natural offshoot of this process in that it promises 100% reproducible diagnoses rendered by quantitative processes that are free from many of the biases of human practitioners.

Exploring cytologic features and potential diagnostic challenges of metastatic NUT carcinoma to the parotid gland: A case report and a comprehensive literature review.

NUT carcinoma (NC) is a highly aggressive, poorly differentiated carcinoma that harbors a t(15:19) translocation, leading to the fusion of the NUTM1 gene. While the upper aerodigestive tract along the midline (head, neck, thorax, and mediastinum) is commonly reported as the primary site of NC, subsequent cases have emerged in diverse locations. Achieving a definitive diagnosis based solely on morphology is challenging; however, it can be achieved using immunohistochemistry (IHC) specific to the NUT antibody or by demonstrating the characteristic BRD4::NUTM1 fusion. Accurate and timely diagnosis can potentially inform patient management and guide treatment. While histologic documentation of NC is commonly found, there is a limited description of its cytologic features. A 39-year-old male with a history of sinonasal squamous cell carcinoma (SCC) presented with a right parotid mass aspirated via fine needle aspiration cytology (FNA). Histologic examination of the previous sinonasal pathology reviewed at our institution revealed sheets of primitive-appearing, monotonous, undifferentiated cells with distinct, prominent nucleoli. Additionally, there were foci of abrupt keratinization, accompanied by a notable neutrophilic infiltrate. The initial diagnosis of SCC was reclassified to NC and confirmed through NUT IHC and molecular testing. Although the parotid FNA initially suggested the possibility of a variety of small round blue cell tumors, it exhibited morphological similarities to the sinonasal tumor, leading to the diagnosis of metastatic NC. Cytomorphologic features of NC are limited and can overlap with various small round blue cell tumors. Correct classification is especially pivotal in the era of targeted therapy, considering the ongoing development and evaluation of BET inhibitors targeting BRD4.

Adjuvant Radiation Therapy for Salivary Duct and Epithelial Myoepithelial Salivary Carcinoma.

Salivary gland cancers are rare in general and salivary duct carcinoma and epithelial myoepithelial carcinomas are rare subtypes. This topic discussion will review the characteristics of these uncommon cancers. Additionally, it will briefly discuss available guidelines for salivary cancers and summarize author opinions on the role of adjuvant radiation therapy for these cases.

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.

Exploring the atypia of undetermined significance: Malignant ratio, ThyroSeq v3 positive call rate, molecular-derived risk of malignancy, and risk of malignancy as possible quality metric tools in thyroid cytology.

BACKGROUND: The atypia of undetermined significance (AUS) category is heterogeneous, leading to variations in its use. To prevent excessive usage, the AUS rate should be ≤10%. Although this recommendation aims to maintain diagnostic quality, it lacks supporting data. The AUS:Malignant (AUS:M) ratio has been proposed as a metric tool to evaluate AUS use. Furthermore, integrating ThyroSeq v3 (TSV3) positive call rate (PCR) and the molecular-derived risk of malignancy (MDROM) have been put forward as performance improvement tools. The authors reviewed their AUS:M ratios, TSV3 PCR, MDROM, and ROM. METHODS: Thyroid aspirates evaluated in the laboratory (from August 2022 to September 2023) by seven cytopathologists (CPs) were identified. AUS:M ratio, MDROM, ROM, and TSV3 PCR results for the laboratory and each CP were recorded and analyzed. RESULTS: A total of 2248 aspirates were identified (462 AUS and 80 malignant). The AUS:M ratio for the laboratory was 5.8 (CPs range, 2.8 to 7.3). The TSV3 PCR for the laboratory was 23% (CPs range, 11% to 41%). The MDROM for the laboratory was 19% (CPs range, 9% to 31%), whereas the ROM was 36% (CPs range, 29% to 50%). Linear regression analysis of AUS:M ratio versus TSV3 PCR and MDROM demonstrated a moderate positive correlation but a weak negative correlation to the ROM. Deviations from established targets were attributed to multiple factors. CONCLUSION: The findings of this study underscore the importance of using a combination of metrics to evaluate diagnostic practices. By dissecting the practice patterns of each CP, the authors can measure different aspects of their performance and provide individualized feedback.

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.

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.

Atypia of undetermined significance and ThyroSeq v3-positive call rates as quality control metrics for cytology laboratory performance.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) recommends an upper limit of 10% for atypia of undetermined significance (AUS). Recent data suggest that this category might be overused when the rate of cases with molecular positive results is low. As a quality metric, the AUS and positive call rates for this facility's cytology laboratory and each cytopathologist (CP) were calculated. METHODS: A retrospective analysis of all thyroid cytology cases in a 4.5-year period was performed. Cases were stratified by TBSRTC, and molecular testing results were collected for indeterminate categories. The AUS rate was calculated for each CP and the laboratory. The molecular positive call rate (PCR) was calculated with and without the addition of currently negative to the positive results obtained from the ThyroSeq report. RESULTS: A total of 7535 cases were classified as nondiagnostic, 7.6%; benign, 69%; AUS, 17.5%; follicular neoplasm/suspicious for follicular neoplasm, 1.4%; suspicious for malignancy, 0.7%; and malignant, 3.8%. The AUS rate for each CP ranged from 9.9% to 36.8%. The overall PCR was 24% (range, 13%-35.6% per CP). When including cases with currently negative results, the PCR increased to 35.5% for the cytology laboratory (range, 13%-42.6% per CP). Comparison analysis indicates a combination of overcalling benign cases and, less frequently, undercalling of higher TBSRTC category cases. CONCLUSIONS: The AUS rate in the context of PCR is a useful metric to assess cytology laboratory and cytopathologists' performance. Continuous feedback on this metric could help improve the overall quality of reporting thyroid cytology.

Parsing the thyroid cytopathology suspicious for malignancy diagnosis through molecular-derived risk of malignancy and other related parameters: Insights into nodule characteristics and practice patterns.

INTRODUCTION: Thyroid cytopathology cases with suspicious for malignancy (SFM) diagnosis often result in resection. However, molecular testing offers details that may provide additional insights. In this study, the molecular profiles of SFM cases from two institutions that routinely used ThyroSeq v3 (TSV3) were examined. MATERIALS AND METHODS: Following institutional review board approval, SFM thyroid cytopathology cases with TSV3 results were retrieved from the databases of two institutions. Molecular information including molecular-derived risk of malignancy (MDROM), cytologic-histologic correlation data, and other related parameters were calculated. Statistical comparisons were made with a p <.05 considered significant. RESULTS: The core data set comprised 114 SFM cases that passed TSV3 quality assurance. All TSV3 results were reported as positive or negative for genomic alterations and all except five cases provided a probability of malignancy estimate. The overall combined baseline MDROM of 75.7% (95% CI, 70.0-81.4) was comparable to the risk of malignancy (74%) published in the Bethesda System. There was a statistically significant difference between the combined MDROMs of resected and unresected cohorts (79.0% vs 58.6%; p = .0153). Interestingly, the MDROMs of the resected cohorts from the two institutions were statistically different (75.0% vs 85.3%; p = .020). Cytologic-histologic correlation revealed malignant outcome in 88.5% of resected cases. CONCLUSIONS: Molecular analyses of SFM cases demonstrated higher risk genomic alterations that were associated with histologically overt neoplasms, resulting in increased malignancy outcome compared to baseline. MDROM analysis revealed differences in the cytopathologic practice patterns regarding follicular-patterned neoplasms at the two institutions.

A Triumvirate:: Correlating Thyroid Cytopathology, Molecular Testing, and Histopathology.

Risk stratification is essential in the preoperative evaluation and management of thyroid nodules, most of which are benign. Advances in DNA and RNA sequencing have shed light on the molecular drivers of thyroid cancer. Molecular testing of cytologically indeterminate nodules has helped refine risk stratification, triage patients for surgery, and determine the extent of surgery. Molecular platforms with high negative predictive values can help identify nodules that may be spared surgery and can be managed conservatively. Here we discuss the importance of integrating cytomorphologic, molecular, and histologic features to help avoid errors and improve patient management.

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.