Biphenotypic Branchioma: A Better Name Than Ectopic Hamartomatous Thymoma for a Neoplasm with HRAS Mutation.

Ectopic hamartomatous thymoma is a rare neck lesion originally thought to represent a non-neoplastic hamartoma, even though thymic origin has been questioned, and there is uncertainty about whether the lesion is a neoplasm. We investigated the genetics by performing targeted next generation sequencing (NGS). Three cases were identified from the authors' consultation files. A custom, targeted NGS panel including 1385 pan-cancer-related genes was performed on all cases. Three patients included 2 males and 1 female, aged 50, 58 and 70 years, respectively (mean 59.3 years), with tumors arising in the low anterior neck. All cases showed classical histologic features of EHT, with one case showing intraductal carcinoma in association with the EHT. By targeted NGS, one case harbored a hotspot HRAS mutation (p.Gln61Lys), while the other two cases only showed non oncogenic variants. Dual mesoderm and endoderm derivation/differentiation (biphenotypic) has been previously recognized, with epithelial and myoepithelial components, and arising from the apparatus contributing to neck development (branchial apparatus). Thus, EHT has been shown to have genetic alterations in HRAS. These findings, without evidence of thymic derivation or an ectopic tissue location, strongly support that EHT is a true neoplasm. The name biphenotyic branchioma more correctly reflects the true nature of this dual mesoderm and endoderm derived tumor occurring in the lower neck.

Reproducibility of endocervical curettage diagnoses.

OBJECTIVE: To estimate overall interobserver variability of histopathology diagnoses on endocervical curettage (ECC) specimens. METHODS: Five study pathologists, blinded to the original diagnosis, reviewed archived ECC specimens initially interpreted as normal, low-grade dysplasia, and high-grade dysplasia. We assessed interobserver agreement and agreement between pathologists using the κ statistic and analyzed the effect of reducing diagnostic choices to two categories (one method using "normal and dysplasia" and another method using "normal and low-grade" and "high-grade or worse"). RESULTS: A total of 90 specimens were reviewed. The overall observer agreement was moderate (κ = 0.52). For specific diagnoses, cases interpreted as normal or high-grade dysplasia demonstrated greater agreement than those interpreted as low-grade dysplasia. Individual pathologists' comparison κ values ranged from 0.31 to 0.80. Changing diagnostic options to a two-tiered system resulted in significant improvement in κ values for only 1 of 36 pathologist comparisons. Using the gynecologist pathologist consensus interpretation, study pathologists downgraded 44% of cases originally interpreted as high-grade. CONCLUSION: Interobserver agreement in the interpretation of ECC specimens is at best moderate, even between those with additional experience and training in gynecologic pathology. Furthermore, reducing diagnostic options to two categories did not improve agreement. It is concerning that important clinical decisions may be made based on an ECC diagnosis that is moderately or poorly reproducible. LEVEL OF EVIDENCE: II.