Myoepithelioma-like hyalinizing epithelioid tumors of the palm: A case report

Abstract

Myoepithelioma-like hyalinizing epithelioid tumors (MHETs) are distinct soft tissue neoplasms characterized by their unique histological presentation, including myoepithelioma-like hyalinization and an epithelioid-cell pattern. A defining molecular characteristic of these tumors is the presence of a novel OGT::FOXO gene fusion. Their distinct morphology makes diagnosis challenging because they can be mistaken for other soft tissue tumors. We report the case of a 71-year-old man who was admitted to our hospital with a 1-year history of a palpable mass on the left palm. Physical examination revealed a well-defined, mobile mass on the lateral aspect of the left palm, measuring 2.0 × 3.0 cm, with moderate consistency. The tumor was surgically excised, and postoperative pathology based on immunohistochemical staining and tissue morphology confirmed the diagnosis of MHET. The tumor cells exhibited diffuse positivity for CD34 and focal positivity for EMA. At the 3-month follow-up post-surgery, there was no evidence of recurrence or distant metastasis. MHETs are typically observed as superficial, well-circumscribed masses without the histological features of malignancy. Given the distinct tissue morphology and the recent identification of this tumor type, clinicians and pathologists must be aware of these features to facilitate accurate diagnosis and inform treatment strategies.

Background

Myoepithelioma-like hyalinizing epithelioid tumors (MHETs) were first reported by Lee et al. ¹ in 2020, who described two cases of soft tissue neoplasms of the hand resembling myoepitheliomas. Since then, six additional cases have been reported, occurring in the shoulder, foot, thigh, and forearm.^2–6 MHETs are characterized by distinct myoepithelioma-like hyalinization and epithelioid tissue patterns. Furthermore, these tumors may harbor OGT gene fusions. Herein, we present a case of MHET occurring in the palm to provide a clinical reference for the diagnosis and treatment of this emerging category of soft tissue tumors.

Case presentation

A 71-year-old man was admitted to the Affiliated Dongyang Hospital of Wenzhou Medical University on 4 June 2024 with a 1-year history of a progressively enlarging mass on his left palm. The mass had increased in size from that of a soybean to that of a quail egg. On physical examination, a 2.0 × 3.0 cm mass was observed on the lateral aspect of the left palm, with moderate consistency, well-defined margins, and mobility. No local redness, ulceration, or tenderness was noted. The patient exhibited full range of motion in all interphalangeal joints, with good capillary refill and intact sensation in the fingertips.

Ultrasound examination

Ultrasonography revealed a 27 × 21 ×14 mm hypoechoic mass with well-defined boundaries within the subcutaneous tissue of the left palm. The mass was closely adhered to the tendon at its lower edge and appeared to be continuous with a nerve at its inferior pole. The interior echotexture was heterogeneous, with small patchy hypoechoic areas suggestive of liquid components. Color Doppler flow imaging showed relatively abundant blood flow signals. (Figure 1) illustrates the hypoechoic mass within the subcutaneous tissue of the left palm. Differential diagnoses included hemangioma and neurofibroma.

Figure 1.

Ultrasonographic findings. A 27 × 21 ×14–mm hypoechoic mass within the subcutaneous tissue of the left palm, with well-defined borders.

Surgical intervention and postoperative pathology

On 5 June 2024, the left palm mass was surgically excised through a 2.5-cm incision. After dissecting the subcutaneous tissue, a 2.0 × 3.0 cm tumor was encountered and was clinically suspected to be a neurofibroma. Gross examination of the excised specimen revealed a single nodule measuring 2.5 × 2 × 1.3 cm, with a grayish-white to grayish-yellow appearance and a moderately firm texture upon sectioning. Microscopic examination revealed a well-circumscribed tumor with a nodular or lobulated configuration. A myxoid chondroid matrix was observed within the nodules. The peripheral fibrous septa displayed a hyaline collagenous matrix with features of sclerotic glassy degeneration. Epithelioid cells were observed in certain regions, exhibiting stellate to short spindle-shaped transformations, eosinophilic cytoplasm, and irregularly contoured nuclei. These cells showed no significant atypia or mild atypia, with no evident mitotic figures or signs of necrosis. In some regions, the tumor cells exhibited a signet ring-like appearance, characterized by clear vacuolated cytoplasm and nuclei displaced to the periphery. The stroma was rich in myxoid matrix (Figure 2(A) to (C)). Immunohistochemical staining revealed that the tumor cells exhibited diffuse positivity for CD34, focal positivity for EMA, positivity for desmin, and partial positivity for cytokeratin (Figure 2(D) to (F)). Conversely, SMA, S-100, SOX-10, p63, calponin, CD117, and MyoD1 were negative. The proliferative index, indicated by Ki-67, was approximately 1%. The combination of postoperative histopathology and immunohistochemical analysis confirmed the diagnosis of MHET of the left palm.

Figure 2.

Pathological morphology and immunohistochemistry of this case. (A) The tumor has distinct margins and is arranged in a nodular or lobulated pattern. Some areas exhibit a myxoid chondroid matrix. The boundary shows a clear fibrous capsule, and the fibrous septa between nodules display a hyaline collagenous matrix with sclerotic glassy degeneration (hematoxylin and eosin [H&E], ×50). (B) The tumor cells are epithelioid, with transitions from stellate to short spindle-shaped forms. The cytoplasm is eosinophilic, the nuclei are irregular, and no significant atypia or mitotic activity is observed. No evidence of necrosis is present (H&E, ×200). (C) In some areas, the tumor cells exhibit a distinct signet ring-like change, with clear vacuolated cytoplasm and displaced nuclei. The stroma contains an abundant myxoid matrix (H&E, ×400). (D) The tumor cells exhibit strong CD34 expression (immunohistochemistry, ×100). (E) The tumor cells express EMA (immunohistochemistry, ×400) and (F) the tumor cells express cytokeratin (immunohistochemistry, ×100).

Outcome and follow-up

No adjuvant radiotherapy or chemotherapy was administered postoperatively. At the 2-month follow-up, there was no evidence of recurrence or distant metastasis.

Consent

The patient consented to all examinations and treatment. Written informed consent was obtained from the patient for the publication of this report and any accompanying images.

Discussion

MHETs typically affect young to middle-aged individuals (age, 18–57 years) without sex predilection (four cases in males and four in females have been reported). Our case shares morphological and immunohistochemical features with previously reported cases. MHETs have been described as well-circumscribed nodules on imaging and gross examination, with a grayish-white cut surface and a size range of 1–6 cm.

Microscopic examination has revealed that MHETs are well-circumscribed tumors with a predominance of epithelioid cells, arranged in cord- and nest-like patterns within a hyalinized to myxoid stromal background. Minimal cellular atypia and an absence of mitotic activity are observed. Additionally, some areas contain signet ring-like cells characterized by vacuolated cytoplasmic changes, ill-defined whorls, and perivascular cell aggregates. Focal reticulin patterns were observed in two cases, ² along with hyalinization of the vascular walls. ⁴ Immunohistochemically, all cases showed diffuse positivity for CD34 and focal positivity for EMA. S100, GLUT1, and claudin-1 were consistently negative, whereas cytokeratin demonstrated positive or partial positive expression in two reported cases,^1,3 including ours. Myoepithelial markers such as SMA, p63, and GFAP were uniformly negative, ruling out the possibility of myoepithelioma. In terms of molecular genetics, RNA-based next-generation sequencing has revealed that these tumors primarily harbor gene fusions involving OGT and the FOXO family, including three cases with OGT::FOXO3 fusion,^1,6 two cases with OGT::FOXO1 fusion,^2,4 two cases with OGT::FOXO4 fusion, ³ and one case with OGT::CITED1 fusion. ⁵

MHETs exhibit distinct histological and immunohistochemical characteristics; however, differentiation from other neoplasms is required. Below, we outline key distinguishing features of MHETs compared to other similar tumors: 1. Soft tissue myoepithelial tumors share morphological similarities with MHETs, presenting as lobulated masses with epithelioid cells and hyalinized or myxoid stroma. Immunohistochemistry typically shows positivity for EMA and cytokeratins; however, the absence of S100 protein and positivity for CD34 are inconsistent with a myoepithelial lineage. In contrast, soft tissue myoepitheliomas are immunohistochemically positive for cytokeratins (approximately 93%) and S100 (approximately 87%), ⁷ with p63 and GFAP showing variable positivity. Myoepithelial carcinomas exhibit greater cellular atypia, frequent mitoses, rare glandular structures, and infiltrative growth, carrying a higher risk of metastasis and being associated with EWSR1 gene translocations in over 50% of cases.^8,9 2. Extraskeletal myxoid chondrosarcoma, which commonly occurs in the deep tissues of the lower limbs, is composed of a uniform cell population with eosinophilic cytoplasm and sparse vascularity. These tumor cells are negative for EMA, and most show intact INI1 expression. EWSR1 gene rearrangements are common, with some cases harboring EWSR1::NR4A3 fusions. ¹⁰ 3. Ossifying fibromyxoid tumors present a lobulated structure, with epithelioid cells embedded in a fibromyxoid stroma. These tumors frequently exhibit mature lamellar bone differentiation at the periphery. Immunohistochemistry is typically positive for S100, and these tumors may demonstrate PHF1 gene rearrangements. ¹¹ 4. Epithelioid sarcomas are infiltrative tumors with indistinct borders. The proximal and classic types are the most common. The proximal type is characterized by greater cellular atypia and rhabdoid changes, whereas the classic type often exhibits nodular or annular arrangements surrounded by collagen fibers, central necrosis, granulomatous changes, and eosinophilic cytoplasm. Immunohistochemistry reveals positivity for CKpan, CK19, and CD34, with INI1 loss being a defining genetic feature. ¹² 5. Sclerosing epithelioid fibrosarcomas are composed of scattered epithelioid cells within a sclerotic stroma, with some areas exhibiting nesting or cord-like arrangements. Immunohistochemistry often shows MUC4 positivity, and gene fusions, such as EWSR1::CREB3L1 (approximately 60%) or FUS rearrangements (approximately 10%), are detected. ¹³ 6. Epithelioid hemangioma features epithelioid cells arranged in cords or nests within a myxoid stroma. These tumors express CD31 and CAMTA1 and often harbor WWTR1::CAMTA1 gene fusions. ¹⁴ 7. Pseudomyogenic hemangiomas consist of a mixture of spindle and epithelioid tumor cells within a sclerotic background, with vascular endothelial differentiation. Most cases demonstrate FOSB gene rearrangements. ¹⁵ 8. Sclerosing perineuriomas, which commonly occur in the hands, are characterized by oval epithelioid cells embedded within a densely sclerotic stroma. Immunohistochemistry reveals EMA positivity, but cytokeratin markers are absent. ¹⁶

MHETs typically present as superficial, well-circumscribed lesions without overt histological features of malignancy, indicating potentially benign biological behavior or indeterminate malignant potential. However, incomplete resection may contribute to recurrence, particularly in cases in which complete surgical excision is not feasible. Close postoperative follow-up is therefore essential. Given the limited number of reported MHET cases and the absence of long-term follow-up data, further clinical research is necessary to better understand the biological behavior of these tumors.

In conclusion, we report a case of MHET with distinct histological features and a specific immunohistochemical profile. However, owing to potential overlap with other malignant or intermediate-grade soft tissue tumors, there is a risk of misdiagnosis and inappropriate treatment. A thorough understanding of the tumor’s histological morphology, immunohistochemical profile, and molecular genetics is crucial for accurate prognostic assessment and appropriate therapeutic decision making. Although MHETs are currently considered benign or of intermediate malignancy, the rarity of this tumor and the lack of large-scale case studies warrant further clinical research to fully elucidate its biological behavior.