Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules.

BACKGROUND: Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy. METHODS: This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed. RESULTS: Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III-IV cytology nodules. Most positive samples had RAS-like (41.7%), followed by BRAF-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS-like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria. CONCLUSIONS: Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III-IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.

Risk stratification of parotid neoplasms based on intraoperative frozen section and preoperative fine needle aspiration cytology.

PURPOSE: This study aims to determine the relationship of frozen section (FS) to final histology and determine how incorporating FS may change preoperative malignancy risk estimates based on preoperative fine needle aspiration cytology (FNAC). The secondary aim is to determine if FS is useful in influencing intraoperative decision-making. METHODS: Retrospective review of 426 intraoperative FS for parotidectomies performed for primary parotid lesions. RESULTS: Risk of malignancy with a benign FS was 2.5%, with indeterminate 36.1%, and with malignant 100%. Incorporating FS to fine needle aspiration for cytology helped to stratify malignancy risk especially in the Milan categories of atypia of undetermined significance, neoplasm of uncertain malignant potential and non-diagnostic categories, where a malignant FS increased malignancy risk significantly. FS was only able to identify 11% of high-risk histological subtypes for which a neck dissection would be recommended. CONCLUSIONS: FS may be used to stratify malignancy risk intraoperatively but has limited utility in clinical decision-making to perform a neck dissection and more extensive parotid resection in high-risk histological subtypes.

Favourable outcome of AIDS-related multi-centric central nervous system Epstein-Barr virus-associated smooth muscle tumour with surgery and adjuvant radiation therapy: a case study and literature review.

Epstein-Barr virus-associated smooth muscle tumour (EBV-SMT) is a unique condition which affects immunocompromised patients. We describe the favourable outcome of a patient with acquired immune deficiency syndrome (AIDS)-related multi-centric EBV-SMT involving the posterior fossa and spine treated with surgery and adjuvant volumetric modulated arc therapy comprising 50 Gy in 25 fractions to four sites initially to the brain and lumbar spine followed by sixth to ninth thoracic vertebrae (T6-T9) and sacrum a year later. Reported literature suggests that AIDS-related EBV-SMTs are more sensitive to radiotherapy. However, compliance to the highly active anti-retroviral therapy is paramount in preventing future recurrence. This case also emphasises the importance of multidisciplinary management in ensuring the best possible outcome.

Risk stratification of fine-needle aspiration cytology of parotid neoplasms based on the Milan system-Experience from a tertiary center in Asia.

BACKGROUND: The recently described Milan system provides a unified way of categorizing salivary gland fine-needle aspiration (FNA) cytology. We aim to use this system to stratify risk of malignancy in parotid FNAs. METHODS: In this retrospective case series, 376 FNAs were preoperatively performed for 573 parotidectomies over 14 years. RESULTS: Risk of malignancy on FNA is as follows: nondiagnostic 14.5%, non-neoplastic 26.7%, atypia of undetermined significance 29.3%, benign neoplasm 2.7%, neoplasm of uncertain malignant potential 19.1%, suspicious for malignancy 87.5%, and malignant 100%. The specific diagnoses of pleomorphic adenoma and Warthin tumor on FNA have high positive predictive value of 97.5% and 96.6%, respectively. Multivariate regression associates smaller size of lesion with a nondiagnostic or indeterminate result. Seniority of operator is associated with a lower likelihood of a nondiagnostic result. CONCLUSIONS: This large Asian series validates the Milan system as a valuable tool in stratifying malignancy risk of parotid FNAs.

Multiple intraneural glomus tumors on a digital nerve: case report.

Glomus tumors are soft-tissue tumors that are commonly found in the hand. Intraneural glomus tumors, however, are rare, and the few reported cases are mostly solitary tumors. We present a woman with a symptomatic swelling on her finger whose imaging findings suggested multiple tumors on the digital nerve, most compatible with a neuroma. Surgical excision and histology, however, confirmed the presence of multiple glomus tumors of the digital nerve. The patient's symptoms resolved after surgery. We describe the biology, typical presentation, and clinico-pathologic features of glomus tumors associated with a peripheral nerve and explore issues that the clinician should consider with multiple tumors.

Value of A103 (melan-A) immunostaining in the differential diagnosis of ovarian sex cord stromal tumours.

AIMS: To assess A103 (melan-A) immunoreactivity in a range of ovarian sex cord stromal tumours and to evaluate it for the differential diagnosis of other neoplasms. METHODS: Paraffin embedded tissue sections from 45 sex cord stromal tumours and 44 potential histological mimics were examined immunohistochemically using the antibody A103. The sex cord stromal group included 21 adult granulosa cell tumours (AGCT), two juvenile granulosa cell tumours (JGCT), eight tumours showing Sertoli cell or Sertoli-Leydig cell differentiation, two unclassified tumours, two gonadoblastomas, one sex cord tumour with annular tubules, two steroid cell tumours, five thecomas/fibrothecomas, and two sclerosing stromal tumours. The histological mimics include 14 primary ovarian carcinomas, 13 metastatic carcinomas, four carcinoid tumours, four lymphomas, three endometrioid stromal sarcomas, two ovarian tumours of probable Wolffian origin, and one case each of small cell carcinoma, desmoplastic small round cell tumour, melanoma, and primitive neuroectodermal tumour. RESULTS: A103 immunoreactivity was identified in 25 sex cord stromal tumours including 10 AGCT, two JGCT, six Sertoli/Sertoli-Leydig cell tumours, two steroid cell tumours, three thecomas/fibrothecomas, and two sclerosing stromal tumours. Of the potential histological mimics, staining was present only in the two ovarian tumours of probable Wolffian origin and the melanoma. Immunoreactive stromal cells were noted in a minority of cases. Normal hilus cells and rete ovarii epithelium also expressed A103. CONCLUSIONS: A103 is a moderately sensitive and specific marker of sex cord stromal differentiation within the range of tumours examined in this study and as such is a valuable adjunct to other immunocytochemical markers in the assessment of diagnostically problematic ovarian tumours. The staining of normal and neoplastic Wolffian elements merits further investigation.