# Clinicopathological analysis of hyalinizing clear cell carcinoma in the head and neck

**Authors:** Xiaoli Zhao, Donglin Ma, Yahui Li, Dongmei Yang, Yingshi Piao

PMC · DOI: 10.1016/j.bjorl.2025.101676 · 2025-07-29

## TL;DR

This study analyzes hyalinizing clear cell carcinoma in the head and neck, showing how combining imaging and lab techniques can improve accurate diagnosis.

## Contribution

The study provides a clinicopathological analysis of HCCC using a combination of imaging and molecular techniques to improve diagnostic accuracy.

## Key findings

- HCCC tumors show characteristic histological features including nests and cords of clear and eosinophilic cells in a hyaline matrix.
- Immunohistochemical markers like CK7, P63, and CK5/6 are positive, while S100, SMA, and GFAP are negative.
- EWSR1 gene rearrangement was detected in all nine patients using fluorescence in situ hybridization.

## Abstract

•Hyalinizing Clear Cell Carcinoma (HCCC) is a rare, low-grade malignant tumor.•HCCC is frequent misdiagnosis.•Combination of analytical techniques can be used to accurately diagnose HCCC.

Hyalinizing Clear Cell Carcinoma (HCCC) is a rare, low-grade malignant tumor.

HCCC is frequent misdiagnosis.

Combination of analytical techniques can be used to accurately diagnose HCCC.

To study clinicopathological features and differential diagnosis of hyalinizing clear cell carcinoma in the head and neck.

A retrospective analysis was performed patients with hyalinizing clear cell carcinoma in the head and neck, who underwent surgical resection in Beijing Tongren Hospital affiliated to Capital Medical University from January 2014 to May 2024. The clinical features of HCCC were analyzed by computed tomography and magnetic resonance imaging. Tumor sections were further characterized using hematoxylin and eosin staining, immunohistochemistry, and fluorescence in situ hybridization.

There were 4 male and 5 female cases in 9 patients. The age range was 28–84 years-old, the middle age was 60 years-old. 9 patients, 5 in the nasopharynx, 2 in the base of the tongue, and 2 in the oropharynx. At the cellular level, the HCCC tumors were composed of transparent and eosinophilic cells (in various ratios), which were typically arranged into nests, cords, and trabeculae, and embedded in a glassy hyaline substance. Immunohistochemical evaluation showed positivity for CK7, P63, P40, CK5/6, and negativity for S100, SMA, GFAP, and calponin. Fluorescence in situ hybridization revealed EWSR1 rearrangement in all the nine patients evaluated.

Hyalinizing clear cell carcinoma is a rare low-grade salivary gland carcinoma that mostly occurs in the minor salivary glands. They had an indolent disease course, with few metastases. Our study shows that the above combination of analytical techniques can be used to accurately characterize and diagnose HCCC.

Level 1.

## Linked entities

- **Genes:** EWSR1 (EWS RNA binding protein 1) [NCBI Gene 2130]
- **Proteins:** KRT7 (keratin 7), RPE65 (retinoid isomerohydrolase RPE65), IL9 (interleukin 9), ck56 (hypothetical protein), S100A1 (S100 calcium binding protein A1), SMN1 (survival of motor neuron 1, telomeric), GFAP (glial fibrillary acidic protein), Chd64 (transgelin calponin-3)

## Full-text entities

- **Genes:** KRT7 (keratin 7) [NCBI Gene 3855] {aka CK7, K2C7, K7, SCL}, SMN1 (survival of motor neuron 1, telomeric) [NCBI Gene 6606] {aka BCD541, GEMIN1, SMA, SMA1, SMA2, SMA3}, GFAP (glial fibrillary acidic protein) [NCBI Gene 2670] {aka ALXDRD}, S100A1 (S100 calcium binding protein A1) [NCBI Gene 6271] {aka S100, S100-alpha, S100A}, EWSR1 (EWS RNA binding protein 1) [NCBI Gene 2130] {aka EWS, EWS-FLI1}, TP63 (tumor protein p63) [NCBI Gene 8626] {aka AIS, B(p51A), B(p51B), EEC3, KET, LMS}
- **Diseases:** Hyalinizing clear cell carcinoma (MESH:D002292), salivary gland carcinoma (MESH:D012468), metastases (MESH:D009362), HCCC tumors (MESH:D009369)
- **Chemicals:** hematoxylin (MESH:D006416)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12329295/full.md

---
Source: https://tomesphere.com/paper/PMC12329295