Recurrent Hyalinizing Clear Cell Carcinoma of the Base of Tongue with High-Grade Transformation and EWSR1 Gene Rearrangement by FISH

Abstract

Hyalinizing clear cell carcinoma (HCCC) is a rare, low-grade salivary gland tumor with clear cells and hyalinized stroma. Prognosis of HCCC is excellent with few cases metastasizing to the lymph nodes and lung. We present a case of a 61-year-old male with recurrent HCCC on the base of tongue. Histologic examination revealed sheets of clear and eosinophilic cells with a background of a myxoid-like matrix. In addition, large, bizarre malignant cells, focal necrosis, and atypical mitotic figures were identified. By immunohistochemistry, the clear cells were positive for CK18, EMA and vimentin, focally positive for CK7 and CD10, but negative for p63, HMWK, SMA and calponin. A metastatic renal cell carcinoma was considered a possibility but the tumor was called "poorly-differentiated carcinoma, NOS". The patient underwent primary radiotherapy. A recurrence was identified at 10 months follow-up. A biopsy of the recurrent tumor showed clear cell differentiation and a predominant cribriform pattern with focal cords of eosinophilic cells invading the stroma. In contrast to the original tumor, no mitotic figures, atypia or necrosis were identified. The combination of lower grade and different architectural patterns appeared markedly different than the previous biopsy and the immunohistochemical pattern was also different. The recurrent tumor showed diffuse positivity for p63 and HMWK. It was negative for CD10, vimentin, SMA and calponin. Fluorescence in situ hybridization (FISH) analysis was positive for rearrangement of the EWSR1 gene in both samples, confirming that this represented a recurrence of the same tumor. It also confirmed that the initial tumor was a HCCC with high-grade transformation.

Hyalinizing Clear Cell Carcinoma of Salivary Gland: A Review and Update

“…HCCC demonstrates a squamous line of differentiation without true myoepithelial marker expression [1]. HCCC has an excellent overall behavior although a growing number of cases are showing high-grade features [23] or unusual behavior (personal observations). There is no rationale at this time for a grading system.…”

“…However, we have recently seen several cases that have had focal or significant necrosis (personal observation). One of these was recently reported as a HCCC with high-grade transformation (dedifferentiation) [23] and some cases have shown basaloid morphology [9]. Of these basaloid cases, two have shown EWSR1 rearrangement by FISH while a third recent case was not tested.…”

“…Only one documented mortality due to disease has been described [24], although an additional ''palliative'' case has been reported [22]. The tumors have a propensity for locoregional recurrence in the order of 12-17 % [9,15,23] and occasional lymph node [1] or distant metastases [15] have been noted. Solar et al reported a 25 % lymph node positivity rate in a review of reported cases [5]; however, this is in sharp contrast to our large series which found no lymph node or distant metastases with reasonable followup (mean 48 months) [9].…”

Adamantinoma-Like Ewing Sarcoma Mimicking Basal Cell Adenocarcinoma of the Parotid Gland: A Case Report and Review of the Literature

“…The hyalinization is typically peritumoral and sharply delineated from the remainder of the intervening fibrocellular stroma. Most tumors are low grade and clear to eosinophilic in appearance but high-grade transformation may occur [24]. In our case the absence of any typical hyalinizing clear cell carcinoma stromal or cytonuclear features, the CD99 reactivity, pseudorosette formation and ultimately the presence of a FLI1 partner excluded hyalinizing clear cell carcinoma, which shows ATF1 as EWSR1 translocation partner.…”

What the EWSR1-ATF1 Fusion has Taught Us About Hyalinizing Clear Cell Carcinoma

“…This suggests the tumors were still lowgrade, although a formal grading system does not exist for HCCC. We have also seen a case with what we called ''high-grade transformation'' [12] that initially presented as a solid, partially clear cell-containing tumor with mitotic activity and necrosis and lacking squamous differentiation by immunohistochemistry. This tumor re-presented as a typical HCCC in the same site within 1 year of radiation therapy.…”