Neck Paragangliomas Research Articles

Paraganglioma With Intracranial Invasion Demonstrated on 68Ga-DOTATATE PET/CT.

68Ga-DOTATATE PET/CT demonstrates superior sensitivity compared with other cross-sectional and functional imaging techniques in detecting head and neck paragangliomas. It is the primary recommended imaging modality for the evaluation of head and neck paragangliomas, especially in patients suspected of having locally aggressive, multifocal, or metastatic disease, as well as those being considered for targeted peptide-receptor therapy. Herein, we demonstrate the 68Ga-DOTATATE PET/CT findings of a skull base paraganglioma with extensive local invasion and intracranial extension.

Current Management of Head and Neck Paragangliomas: A Multicenter Series With Long-Term Follow-Up.

To improve our knowledge about head and neck paragangliomas (HN-PGL), the clinical characteristics of all the patients with HN-PGL included in the Spanish Registry were analyzed, as well as the treatment modalities and their outcomes. A total of 202 patients, 67.8% women, aged 53.1 ± 17.4, with 264 HN-PGL, from 16 Spanish hospitals, were included. Tumors were located in the carotid body in 61%, jugular bulb in 20.5%, tympanic area in 10.2%, and along the vagal nerve in 6.4%. Multiple tumors developed in 20.8% and metastatic disease in 4%. A genetic study was done in 64.4% and showed a pathogenic variant in SDHx in 50%. These patients were younger, with no sex predominance, and had more multiple and metastatic tumors. Tumors were treated by surgery in 134 patients, radiotherapy in 33, and other treatments in 20, and were observed without active treatment in 41 patients, who were older, more often asymptomatic, and had smaller tumors. Tumors treated with radiotherapy were larger and more often in locations other than the carotid body. After a median follow-up of 80 months (interquartile range: 41-136), 6.9% had died; among the survivors, 48.4% were disease-free, 42.1% stable, and 9.4% had progressed. The rate of sequelae was similar among patients submitted to surgery, radiotherapy, or observation. We could not identify any prognostic factor for progression. Most HN-PGL are localized slow-growing tumors. Long-term survival is high, even in case of metastasis. Although surgery is the most common treatment, radiotherapy and active surveillance are safe approaches.

7553 Thyroid Paraganglioma: A Complex Tale of the Familiar Thyroid Nodule

Abstract Disclosure: V. Moorthy: None. A. Kondapally: None. L.E. Kimball-Ravari: None. Background: Thyroid paragangliomas are rare and often misdiagnosed on fine-needle aspiration (FNA). Clinical Case & Discussion: A 58-year-old female presented with an asymptomatic “cold” thyroid nodule. Ultrasound demonstrated a 2 cm hypoechoic nodule in the isthmus. FNA yielded a follicular lesion of undetermined significance, and genomic sequencing estimated a 50% risk of malignancy prompting the patient to opt for total thyroidectomy. Histopathology and immunohistochemistry (IHC) confirmed the diagnosis of benign paraganglioma (PGL). SDH-B (succinate dehydrogenase subunit B) was notably absent on IHC. Past medical history is significant for hysterectomy for uterine fibroids and obesity, along with a confirmed family history of Hereditary Leiomyomatosis with Renal Cell Cancer (HLRCC). The patient and several family members tested positive for a pathogenic variant of fumarate hydratase (FH) gene implicated in HLRCC and undergo annual MRIs for cancer surveillance. The loss of SDH-B suggests underlying mutation. Germline SDH mutations occur in 20% of patients with pheochromocytoma and PGLs, predisposing to hereditary syndromes. PGLs are catecholamine-secreting neuroendocrine tumors with carotid body and jugular PGLs accounting for 80% of head and neck PGLs (HNPGLs). Thyroid PGLs originate from the inferior laryngeal paraganglia. They are very rare, often non-secretory, and commonly present as asymptomatic solitary nodules. For these reasons, FNA, while contraindicated, is frequently performed. If FNA is considered, pre-procedural alpha-adrenergic blockade is recommended, although catecholamine secretion triggered by FNA is uncommon. Thyroid PGLs are misdiagnosed on FNA as other thyroid neoplasms. Awareness of the more unique cytopathology of thyroid PGLs and a comprehensive IHC can aid in accurate diagnosis. Interestingly, SDH (complex 2) and FH are closely linked enzymes in the Krebs cycle. Emerging evidence correlates germline FH mutations and hereditary pheochromocytoma-paraganglioma. PGLs are less commonly associated with MEN 2A and 2B, NF type 1, VHL, and Carney-Stratakis syndrome and Carney triad. Therefore, additional testing for SDH, RET, VHL and MAX genes was recommended in this case. Total thyroidectomy or lobectomy with or without elective lymph node dissection remains the treatment of choice. Annual 24-hour urine and plasma metanephrine testing will help screen for potential recurrence. Use of GLP1 agonists for weight loss in this patient warrants further genetic and safety evaluation. Clinical Lesson/Conclusion: Often misdiagnosed on FNA, thyroid paragangliomas are rare, with multiple genetic predispositions. FNA is contraindicated and if considered, must be performed after alpha-blockade. Germline SDH mutations are implicated in PGLs and increasing evidence links FH mutations to hereditary PGLs. Presentation: 6/3/2024

Management and follow-up strategies for patients with head and neck paraganglioma.

Head-neck paragangliomas (HNPGLs) are rare tumors with approximately half arising due to germline pathogenic variants (PVs) in succinate dehydrogenase genes (SDHx). Patients with HNPGL have heterogeneous propensity to recur and metastasize. Thus, we aim to assess prevalence and predictors of recurrent (RD) and/or metastatic disease in patients with and without SDHx-related HNPGLs. This cross-sectional study used retrospective data of 214 patients enrolled in six referral centers. Data included sex, age, primary tumor treatment, location, and size, biochemical phenotype, germline PVs, presence of RD (locoregional or new tumor), and/or metastasis. Patients with and without SDHx-related HNPGLs showed 74% and 40% prevalence of RD, respectively. Patients without SDHx-related HNPGLs presented with recurrent tumors only in head-neck regions. The only independent predictor for RD in the entire cohort was presence of SDHx PVs. Metastatic prevalence reached 9%-13%. For patients with SDHx-related HNPGLs, large tumor size (>2.3 cm, OR:50.0, CI:2.6-977.6), young age at initial diagnosis (<42years, OR:27.3, CI:1.8-407.2), and presence of SDHB PV (OR:15.6; CI:1.5-164.8) were independent predictors of metastasis. For patients without SDHx-related HNPGLs, only carotid-body location was an independent predictor of metastasis (OR:18.9, CI:2.0-182.5). Patients without SDHx-related HNPGLs require long-term follow-up due to high prevalence of RD with imaging largely restricted to head-neck regions. As carotid-body HNPGLs have the highest metastatic risk among sporadic tumors, radical treatment with frequent follow-up is suggested until population-based data are available. Importantly, patients with SDHx-related HNPGLs might benefit from early radical treatment when tumors are still small to reduce metastatic risk.

Clinical Characteristics and Outcomes of Tympanomastoid Paragangliomas: A Report from Slovenia.

(1) Background: Head and neck paragangliomas are neuroendocrine tumors that typically originate from the parasympathetic nervous system and are predominantly non-secretory. Their clinical manifestations result from their mass effect on the surrounding tissues. The approach to treating these tumors depends on factors such as their location, size, impact on adjacent structures, and the patient's overall health and preferences. (2) Methods: A retrospective analysis of the management of temporal bone paraganglioma classes A and B (according to the modified Fisch classification) was performed at the University Medical Centre, Ljubljana, between 2011 and 2023. (3) Results: We analyzed 23 cases, 19 of which underwent surgery; complete tumor removal was achieved in 18 of them. Four patients were irradiated due to tumor progression to class C. Three of these four patients initially refused surgery and were treated with radiotherapy (RT) 7, 13, and 18 years after diagnosis. In the fourth patient, complete surgical resection was not achieved and she was treated with RT four years after surgery, due to the growth of the tumor to class C. The average follow-up time from diagnosis was 8.9 years (median 6 years; range 1-26 years). (4) Conclusions: The surgical treatment of patients with class A and B paragangliomas is effective and safe. In cases where surgery is refused but the tumor continues to grow to class C, RT is an alternative and efficient method of controlling tumor growth.

A case of preoperative embolization for a giant hypervascular pancreatic serous cystic neoplasm in pancreaticoduodenectomy

BackgroundPreoperative vascular embolization is an effective strategy for managing meningiomas, neck paragangliomas, renal cell carcinomas, and bone metastasis by reducing the intraoperative bleeding volume and operation time. Although hypervascular tumors also occur in the pancreas, preoperative embolization for these tumors is not commonly practiced. We herein present a case of a giant serous cystic neoplasm (SCN) of the pancreas with significant arterial vascularity that was managed with preoperative interventional radiology and subsequently resected via pancreaticoduodenectomy.Case presentationA 60-year-old man presented with an 8-cm hypervascular tumor located at the head of the pancreas, identified as an SCN on pathologic examination. The tumor had increased by 13 mm over 5 years, necessitating surgical intervention. Computed tomography revealed a substantial blood supply to the tumor from the dorsal pancreatic artery and gastroduodenal artery, both branches of the superior mesenteric artery. To mitigate the risk of severe intraoperative bleeding from this giant hypervascular tumor, branches of the dorsal pancreatic artery and gastroduodenal artery were embolized using metallic coils and further secured using a gelatin sponge 1 day prior to pancreatectomy. During the laparotomy, the tumor appeared to have decreased in size, likely because of reduced distension and congestion. Despite significant adhesions to surrounding tissues secondary to prolonged compression and inflammation, the pancreaticoduodenectomy was completed successfully in 5 h and 15 min with blood loss of 763 mL. The patient was discharged on postoperative day 15 without complications.ConclusionsPreoperative arterial embolization for hypervascular pancreatic tumors might control the risk of massive intraoperative bleeding, contributing to a favorable postoperative outcome. Utilizing interventional radiology for preoperative inflow control is one of the beneficial strategies for pancreatectomy in patients with a giant SCN.

Head and Neck Paragangliomas: 16-year Single-center Experience and Mini Review on Diagnosis, Treatment, and Follow-up.

To investigate head and neck paraganglioma cases treated at a tertiary center from 2007 to 2023. The research includes a thorough examination of published studies that have focused on long-term outcomes. The additional goal is to contribute to the existing knowledge on head and neck paraganglioma, with a particular emphasis on refining diagnostic algorithms, treatment selection, and follow-up procedures. A total of 44 patients were retrospectively analyzed, and 39 were included. Demographic information, symptoms, radiological examination results, types, stages, and postoperative complications were recorded. A review was conducted to select articles that reported single-center experiences with large cohorts, long follow-ups, and different treatment modalities since 2010. The mean age of the patients was 54 years, and the female/male ratio was 3.55:1. Among the 39 cases examined, 18 and 19 were identified as cervical paraganglioma and 19 as temporal bone paraganglioma. All patients initially underwent surgical resection. The mean follow-up duration was 5.42 years. Four residual cases and two recurrences were identified postoperatively, and a Gamma Knife was used as additional treatment. Subsequently, 17 articles were selected and summarized, and then a flowchart was prepared showing the possible options for diagnosis, treatment, and follow-up. Preoperative staging is essential for surgical planning and predicting potential intraoperative complications. Based on our findings and review of the articles, we have prepared a flowchart that includes all possibilities depending on the tumor stage to help in the diagnosis, treatment, and follow-up of head and neck paragangliomas.

Reconstruction of internal carotid artery in the resection of paraganglioma of head and neck

Objective:This study aims to discuss the necessity，surgical method and effect of reconstruction of internal carotid artery （ICA） in the resection of paraganglioma of head and neck. Methods:We retrospectively analyzed the data of the patients who underwent head and neck paraganglioma resection and ICA reconstruction in Peking Union Medical College Hospital from May 2015 to August 2023. The demographic characteristics, preoperative examinations, diagnoses, surgical techniques, and follow-up information were collected. Results:Six patients were enrolled, including four females and two males, with an average age of（39.8±13.0） years. All the patients presented mainly complaining local masses with or without pain. Four cases underwent surgery through Fisch infratemporal fossa approach type A+B, and one through approach type A and one through transcervical approach. Five patients had vascular reconstruction using the great saphenous vein while one patient used an artificial vessel. The average follow-up period was（43.8±31.6） months. One patient had tumor recurrence after 3 years and underwent second surgery to remove the residual tumor, and the other 5 patients had no tumor recurrence. One patient had acute bridging vessel embolism, and the other was found to have occlusion of the bridging vessel at follow-up. Conclusion:Carotid revascularization during resection of paraganglioma of head and neck is an important technique to completely remove the tumor, cure the disease, ensure intracranial blood supply, and reduce cerebrovascular complications. The "pre-reconstruction technique " is an effective method to minimize the duration of brain blood flow interruption, compared to traditional carotid revascularization. Close observation is necessary, along with regular radiological examinations to assess the patency of transplanted vessels, and the residual or recurrent tumors.

Review and prospect of the diagnosis and treatment of head and neck paragangliomas

ead and neck paraganglioma（HNPGL） often originates from the parasympathetic ganglia and is a highly invasive benign tumor. The diagnosis and treatment of this disease with strong heterogeneity is still a challenge. In the future, deep exploration is needed in genetic typing, grading diagnosis and treatment decisions, protection of cranial nerves and new drug treatments to better treat this disease.

Advance in HIF expression and immune microenvironment in pseudohypoxic HNPGL

This article systematically reviewed the pathological features, molecular mechanisms, and tumor microenvironment of head and neck paraganglioma（HNPGL）, with a focus on pseudohypoxic HNPGL. It was demonstrated that pseudohypoxic HNPGL mainly involves multiple gene mutations, such as SDHx and VHL/EPAS1, which affect the stability and activity of HIF protein and exacerbate the development of the tumor. Meanwhile, the paper also analyzed the expression patterns of HIF-1α and HIF-2α in HNPGL, and found that differences in HIF activation may have an impact on the therapeutic response of specific subtypes. In addition, the paper explored the tumor microenvironment of HNPGL and found that immune cells such as macrophages, CD4⁺T cells, and CD8⁺T cells play an important role in the tumor, and the heterogeneity of the immune microenvironment also affects the choice of therapeutic approaches and responsiveness. Through comprehensive analysis, these findings not only contribute to a deeper understanding of the pathogenesis and developmental process of HNPGL, but also provide clues for future personalized treatments for specific subtypes.

The treatment of the head and neck paraganglioma

The treatment of the head and neck paraganglioma

Intratumoral Microbiome in Head and Neck Paragangliomas.

Head and neck paragangliomas (HNPGLs) are rare neoplasms arising from paraganglia of the parasympathetic nervous system. HNPGLs are characterized by high vascularity and are located in proximity to major vessels and nerves, which may be potential sources of microbial invasion in these tumors. There have been no studies in the literature on the microbiota in HNPGLs. Investigation of the microbiome associated with paragangliomas is important for understanding tumor pathogenesis. In this study, we investigated the microbiome composition in two sets of HNPGLs. First, 29 fresh frozen (FF) tissues were subjected to 16S rRNA gene sequencing; concurrently, a panel of candidate laboratory-derived contaminants was investigated. Second, we analyzed microbial reads from whole transcriptome sequencing data obtained for 82 formalin-fixed paraffin-embedded (FFPE) HNPGLs. The bacterial diversity in FF tumors was found to be significantly lower than that observed in FFPE HNPGLs. Based on 16S rRNA gene sequencing, only seven bacterial families were identified as potential tumor inhabitants: Bryobacteraceae, Enterococcaceae, Neisseriaceae, Legionellaceae, Vibrionaceae, Obscuribacteraceae, and Mycobacteriaceae. However, RNA-Seq demonstrated higher sensitivity for identifying microbiome composition and revealed abundant bacterial families that partially correlated with those previously described in pheochromocytomas and extra-adrenal paragangliomas. No viruses were found in HNPGLs. In summary, our findings indicated the presence of a microbiome in HNPGLs, comprising a number of bacterial families that overlap with those observed in pheochromocytomas/paragangliomas and glioblastomas.

Management of bilateral head and neck paragangliomas at a single-institution across four decades.

Bilateral head and neck paragangliomas (HNPGLs) require nuanced management to balance tumor control with functional preservation. All patients seen at a single-institution for bilateral paraganglioma between 1983 and 2023 were retrospectively reviewed. Demographics, genetic testing results, and tumor characteristics were analyzed and compared to treatment modality and cranial nerve outcomes. There were 49 patients with 116 tumors (90 carotid body tumors [CBTs], 15 vagal paragangliomas [VPs], and 11 jugular paragangliomas [JPs]). Twenty-six patients had SDH pathologic variants (PV). Surgical management was more commonly utilized in younger patients (OR: 0.97, 95% CI: 0.950-0.992) and for JPs (OR: 9, 95% CI: 1.386-58.443). In surgical cases, CBTs had a lower risk of postoperative cranial nerve deficits compared to JPs and VPs (OR: 0.095, 95% CI: 0.013-0.692). Younger patients with bilateral HNPGLs, especially those with JP and CBT, are more often treated with surgery. CBTs have lowest risk of cranial nerve deficits after surgery.

Integrated Management of Malignant Head and Neck Paragangliomas: A Case Report and Review of Literature

Integrated Management of Malignant Head and Neck Paragangliomas: A Case Report and Review of Literature

The relationship between clinical characteristics and pathological features in patients with pheochromocytomas/paragangliomas

Objective: To explore the correlation between clinical characteristics and pathological features in patients with pheochromocytoma/paraganglioma (PPGLs). Methods: A case series study. A retrospective analysis was conducted on patients with single and primary PPGLs after postoperative pathological diagnosis who were admitted to Peking Union Medical College Hospital between January 2019 and December 2022. The patients were divided into the Ki-67<3% group and the Ki-67≥3% group with Ki-67 proliferation index of 3% as the threshold. The relationship between clinical and pathological characteristics of PPGLs was analyzed. Results: A total of 399 PPGLs patients were included, with 177 males and 222 females, aged [M(Q1, Q3)] 45.0(35.5, 53.0) years. Among them, 226 (56.6%) cases originated from the adrenal gland, while 104 cases (26.1%) from the retroperitoneum. 20.9% (27/129) of the patients were found to harbor germline mutations of susceptibility genes, with SDHB mutations being the most common (10.1%, 13/129). The Ki-67 staining was performed on 302 cases, with a Ki-67 proliferation index [M(Q1, Q3)] of 2.0% (1.0%, 3.0%). There were 194 cases in Ki-67<3% group and 108 cases in Ki-67≥3% group. Compared with the patients in Ki-67<3% group, the age of onset in Ki-67≥3% group was younger (P=0.029). Compared with the patients with paragangliomas without SDHB or Cluster 1A-related gene mutations, positive 131I-meta-iodobenzylguanidine (131I-MIBG) imaging or negative O-6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry staining, those with SDHB or Cluster 1A-related gene mutations, negative 131I-MIBG imaging or positive MGMT immunohistochemistry staining had a higher Ki-67 index (all P<0.05). Compared with adrenal pheochromocytoma, retroperitoneal paragangliomas had a higher proportion of SDHB mutations and a higher proportion of normetanephrine (NMN) secretory types (all P<0.05). Compared with adrenal pheochromocytoma, the maximum diameter of head and neck paraganglioma tumors was smaller [3.0 (1.9, 3.8) cm vs 4.7 (3.4, 6.4) cm, P<0.001] and the proportion of Ki-67≥3% was higher (61.3% vs 33.8%, P=0.007). Conclusions: PPGLs patients with earlier onset age, SDHB or Cluster 1A-related gene mutations, negative 131I-MIBG imaging, or positive MGMT immunohistochemistry staining tend to have a higher Ki-67 index. Head and neck tumors, though smaller, exhibit a higher proliferation potential.

The Role of Internal Carotid Artery Stent in the Management of Skull Base Paragangliomas.

Background: After two decades from its introduction in the lateral skull base paraganglioma surgery, the indications and results of preoperative internal carotid artery stenting should be critically assessed. Materials and Methods: Monocentric retrospective study on 26 patients affected by head and neck paragangliomas (19 tympanojugular paragangliomas, 4 carotid body paragangliomas, 3 vagal paragangliomas) preoperatively treated with internal carotid artery stents between 2008 and 2023. The preoperative findings, the intraoperative complications and the final surgical results were analyzed. Results: The stent complication rate was less than 3.1%. Self-expanding highly flexible intracranial nitinol stents were applied. In all cases, it was possible to completely mobilize the internal carotid artery and perform a vascular dissection of the tumor. Gross total tumor resection was possible in 85% of cases. The median follow up was 7.83 y (SD +/- 3.93 y). No local recurrence was observed. Conclusions: The preoperative vascular stent facilitates tumor dissection from the internal carotid artery without risk of vascular damage, helping the surgeon to achieve surgical radicality. The vascular stent is indicated in the case of revision surgeries, circumferential involvement of the vessel and in cases with non-insufficient intracerebral crossflow. Procedural complications, temporary antiplatelet therapy and delay of surgery are the limitations of the procedure.

Preoperative embolisation of head and neck paragangliomas - a single-centre experience.

Paragangliomas are neuroendocrine tumours commonly located in the abdomen, thorax, head and neck. The definitive treatment for these tumours is surgical resection, which in some cases can be very challenging due to the involvement of critical neurovascular structures and their high vascularity. Therefore, pre-operative embolisation may be performed to reduce the risk of complications. This study aimed to present our experience with endovascular embolisation of head and neck paragangliomas (HNP). In this single-centre study, we reviewed data from consecutive patients with HNP who underwent pre-operative embolisation from 2017 to 2023. The efficacy of embolisation, the method of embolisation, as well as the rate of complications, were noted. A total of 27 patients (15 females) with an average age of 47 years underwent selective embolisation of HNP. Satisfactory embolisation, defined as occlusion of > 75% of the blood supply, was achieved in 22/27 cases (81.5%). The most commonly used embolic agents included coils and microspheres. With the exception of minor vessel dissections in two patients and embolic agent migration in two patients causing reversible occlusion of the intracranial vessels, there were no other complications associated with embolisation. No neurological deficits occurred in relation to the endovascular procedure. The results of our study indicate that endovascular embolisation of HNP prior to surgical resection is a safe and efficacious procedure, with a relatively low complication rate and associated morbidity.

Response to conformal radiotherapy in head and neck paragangliomas

Response to conformal radiotherapy in head and neck paragangliomas

Basaloid squamous cell carcinoma clinically and radiologically masquerading as a head and neck paraganglioma: a case report and review of the literature

BackgroundThis paper reports the first case of basaloid squamous cell carcinoma clinically and radiologically masquerading as a head and neck paraganglioma.Case presentationA 66-year-old Sinhalese male with unilateral hearing impairment and 7th–12th (excluding 11th) cranial nerve palsies was diagnosed radiologically with a head and neck paraganglioma by magnetic resonance imaging of the brain, which revealed a hypointense and hyperintense punctate mass centered at the jugular fossa with intracranial extension. The ascending pharyngeal artery, recognized as the major feeder, was embolized by percutaneous embolization following digital subtraction angiography. Gross total resection of the tumor was followed by an uneventful postoperative recovery. Combined immunohistochemistry and histopathological morphology revealed a basaloid squamous cell carcinoma, following which the patient completed radiotherapy and is at 3-month follow-up currently.ConclusionThis case report discusses the diagnostic pitfalls and management challenges of this rare entity on the basis of prior evidence, as well as a literature review and clinical and surgical analysis.

Frequent Immunohistochemical Expression of Transcriptional Repressor GATA Binding 1 in Salivary Gland Neoplasms: A Sensitive but Nonspecific Marker.

Salivary gland (SG) neoplasms (SGNs) display considerable immunophenotypic diversity. A significant proportion of SG carcinomas develop metastases with increased diagnostic difficulty at metastatic sites. Transcriptional repressor GATA binding 1 (TRPS1), a novel immunohistochemical marker for breast cancer, has been found to stain certain SGNs. To investigate TRPS1 and SRY-related HMG-box 10 (SOX10) immunoexpression in various SGNs and non-SG carcinomas, head and neck paragangliomas, and head and neck mucosal melanomas. TRPS1 immunoreactivity score (IRS) was determined as negative or low, intermediate, or high positive; SOX10 was reported as negative or positive. One hundred forty-eight SGNs, 5 breast carcinomas, 105 nonbreast-non-SG carcinomas, including 33 head and neck squamous cell carcinomas (HNSCCs), 6 head and neck paragangliomas, and 6 head and neck mucosal melanomas, were assessed for TRPS1. All 23 benign SGNs showed TRPS1 positivity, with the majority having high-positive IRS (17 of 23 cases; 74%). Among 125 SG carcinomas, 115 of 125 (92%) were TRPS1 positive, with high-positive IRS in 94 of 125 (75%), intermediate positive in 15 of 125 (12%), and low positive in 6 of 125 (5%). Among nonbreast-non-SG carcinomas, HNSCC, lung, thyroid, kidney, and ovarian carcinomas showed frequent TRPS1 staining. Nearly half of HNSCCs had high (11 of 18; 33%) or intermediate (4 of 18; 12%) positive IRS. Mean IRS in SG carcinomas was significantly higher than that in nonbreast-non-SG carcinomas (P < .001). None of the TRPS1-positive nonbreast-non-SG carcinomas expressed SOX10. TRPS1 is positive in most benign and malignant SGNs. Its expression in several nonbreast-non-SG carcinomas indicates that it lacks specificity for breast and SG carcinomas, even if considering only high-positive IRS. Addition of SOX10 can increase discriminatory utility of TRPS1.