Epithelioid Sarcoma of the External Auditory Canal: An Uncommon Tumor at an Unusual Site and a Brief Overview of the Literature

Abstract

We present a case (41 years old pregnant female) with epithelioid sarcoma arising in the left external auditory canal. On immunohistochemistry, the tumor cell diffusely expressed cytokeratins and showed patchy expression of ERG and CD34. The neoplastic cells demonstrated uniform loss of INI1-expression. Epithelioid sarcoma arising in the external auditory canal is rare. Awareness that ES may rarely arise at unusual sites is of critical importance in order to apply a broad enough panel in the immunohistochemical study, so a misdiagnosis of carcinoma can be avoided.

Introduction

Epithelioid sarcoma (ES) is an uncommon malignant neoplasm, accounting for less than 1% of all soft tissue sarcomas [1]. While ES has been reported in head and neck locations, the majority of cases occur in the extremities, with head and neck cases estimated at only 1% of all ES cases [2–5]. ES occurring in the head and neck includes both primary and metastatic disease [5–8]. To the best of our knowledge, this is the third reported case of primary ES of the ear (see Table 1) [5, 9]. ES may occur at any age, but there is a distinct peak in young adults, and ES occurs more frequently in males [4]. While patients with ES may have localized disease at presentation, there is frequently local recurrence rate post resection, ranging from 15 to 75% [1, 10–12]. Metastatic spread to regional lymph nodes occurs in 20–45% of cases, while distant metastasis (most commonly to the lungs) occurs in 30–50% of cases [12].

Table 1.

Cases of epithelioid sarcoma of ear in the literature

Source	Gender	Age	Duration of follow up	Alive	Local recurrence	Metastasis
Chase et al. [5]	Male	Not stated	85 months	Yes	No	No
Nayak et al. [9]	Male	7 years	12 months	Yes	No	No
Our case	Female	41 years	Lost to follow up	N/A	N/A	CT neck showed enlarged cervical lymph nodes. No lymph node tissue sampling performed

Case Report

The patient is a previously healthy 41 years old female who was 36 weeks pregnant at the time of presentation. She presented with left external ear pain and discharge. On clinical examination, there was circumferential tumorous involvement of the left external auditory canal (EAC) (Fig. 1a). A computerized tomography (CT) scan revealed an enhancing soft tissue mass present at the left EAC measuring 1.6 × 1.5 cm. There was no extension to the deep neck spaces. There was cortical erosion at the anterior and posterior walls of the ear canal. On magnet resonance imaging (MRI), there was a T1w-isointense and mildly T2w-hyperintense enhancing mass in the left EAC which demonstrated restricted diffusion filling and expansion of the EAC. There was no intra-cranial extension. The tumor eroded the anterior and posterior walls of the auditory canal. The mass was inseparable from the left parotid gland inferiorly and abutted the left internal carotid artery medially. The radiological impression was that of a malignant tumor.

Fig. 1.

Representative images of the left external auditory canal tumor. a Clinical appearance of the tumor in the left external auditory canal. b Tumor cells with spindle cell morphology (Hematoxylin and Eosin stain, × 10 magnification). c Tumor cells with spindle cell morphology (Hematoxylin and Eosin stain, × 20 magnification). d Tumor cells with spindle cell morphology are diffusely positive for CAM5.2 IHC (Immunhistochemical stain with CAM5.2 antibody, × 20 magnification). e Tumor cells with spindle cell morphology show diffuse loss of nuclear expression with INI1 IHC (Immunhistochemical stain with INI1 antibody, × 10 magnification). f Tumor cells with epithelioid morphology (Hematoxylin and Eosin stain, × 20 magnification). g Tumor cells with epithelioid morphology are diffusely positive for CAM5.2 IHC (Immunhistochemical stain with CAM5.2 antibody, × 20 magnification). h Tumor cells with epithelioid morphology show diffuse loss of nuclear expression with INI1 IHC (Immunhistochemical stain with INI1 antibody, × 20 magnification)

Biopsies were obtained from the left EAC mass and following the pathological diagnosis of epithelioid sarcoma, staging CT scans were performed. CT imaging of the neck revealed the presence of multiple enlarged left level II cervical lymph nodes, of which the largest lymph node (size 1.1 cm) demonstrated central hypodensity, possibly representing central necrosis. CT imaging of the thorax and liver revealed no evidence of metastatic disease.

The patient was not a suitable candidate for surgical resection and was offered concurrent chemo- and radiation therapy but defaulted on subsequent follow up and treatment.

Biopsy Findings

Histopathology (Fig. 1)

The biopsy showed neoplastic cells with epithelioid and spindled morphology, admixed with inflammatory cells (including macrophages), and reactive stromal cells. The neoplastic cells exhibit moderately enlarged nuclei with irregular nuclear membranes, and ample cytoplasm. Rhabdoid morphology was not discerned. Mitotic activity was up to 5 mitotic figures per 10 high power fields. No tumor necrosis was identified. There was ulceration of the overlying non-dysplastic squamous epithelium.

Immunohistochemistry (Figs. 1 and 2)

Fig. 2.

CD34 and ERG immunohistochemistry. a In some areas, the tumor cells are positive for CD34 IHC (Immunhistochemical stain with CD34 antibody, × 20  magnification). b In some areas, the tumor cells are positive for ERG IHC (Immunhistochemical stain with ERG antibody, × 20 magnification)

The neoplastic cells were widely positive for pan-cytokeratin AE1/3 and CAM5.2. The neoplastic cells were also patchily positive for ERG and CD34. The tumor cells exhibited complete loss of nuclear INI-1 expression. There was no expression of p63 and CD31 in the neoplastic cells.

Discussion

Epithelioid sarcoma (ES) was first described by Enzinger in 1970, in a series of 62 cases of “a peculiar form of sarcoma that has repeatedly been confused with a chronic inflammatory process, a necrotizing granuloma, and a squamous cell carcinoma” [2]. In this initial series, which predated the era of routine immunohistochemical studies and molecular diagnostics, the differential diagnoses spanned both benign (e.g. granulomatous inflammation) and malignant lesions (e.g. ulcerating squamous cell carcinoma), thereby highlighting its diagnostic difficulty. In the half-century that followed, the understanding of ES has evolved significantly. Apart from the conventional/classic (distal-type) ES, proximal-type ES was described in 1997 by Guillou et al. [13]. Consistent loss of INI1 (hSNF5/SMARCB1) expression by immunohistochemistry was discovered in the vast majority of both conventional and proximal-type ES [14]. While no specific recurrent cytogenetic abnormality been discovered for ES, the frequent presence of chromosome 22q11 (where the SMARCB1 is located) abnormalities lends support the idea that loss of SMARCB1 is implicated in its tumorigenesis [3, 15–17].

Apart from ES, tumors exhibiting loss of INI-1 expression by immunohistochemistry include malignant rhabdoid tumor of the kidney and at extra-renal soft tissue sites, pediatric atypical teratoid/rhabdoid tumor, medullary carcinoma of the kidney, epithelioid malignant peripheral nerve sheath tumor, poorly differentiated chordoma, as well as subsets of extraskeletal myxoid chondrosarcoma and myoepithelial carcinoma [18, 19]. Recently, SMARCB1 (INI-1)—deficient sinonasal carcinomas, SMARCB1 (INI-1)—deficient rhabdoid carcinoma of the gastrointestinal tract, and pancreatic undifferentiated rhabdoid carcinomas with loss of SMARCB1 (INI-1) expression have also been described [20–22]. The plethora of tumors exhibiting loss of INI-1 expression by immunohistochemistry emphasizes that while this is a characteristic feature of ES, it is not (by itself) a specific finding of ES.

To complicate matters further, a very small subset of ES retains INI-1 on immunohistochemistry [23, 24]. It is postulated in such cases that tumorigenesis occurs as a result of abnormalities in other SWI/SNF chromatin re-modelling complex members [24]. Hence, the retention of INI-1 expression on immunohistochemistry does not entirely exclude the possibility of ES.

The typical appearance of classic ES is that of nodular aggregates of fairly uniform plump epithelioid cells and associated geographical necrosis. Cellular atypia is generally mild. Spindled cells may be present, and often merges with the epithelioid cells. In contrast, proximal-type ES typically exhibits multinodular or sheet-like growth pattern with large polygonal cells demonstrating pleomorphic vesicular nuclei and prominent nucleoli. Rhabdoid morphology is frequently present. There is often associated tumor necrosis, but the geographical pattern of necrosis typically seen in classic ES is absent or not as pronounced in proximal-type ES. Spindled cells may also be present in proximal-type ES, but this is not as frequent as classic ES [3, 13, 25].

Classic ES most commonly affects the distal extremities, while proximal-type ES typically affect axial proximal regions, such as limb girdles, pelvis, perineum, mediastinum and trunk [3, 25]. However, both types may occur in either proximal or distal locations [12, 25]. While rare, ES has been described in head and neck locations. Enzinger’s initial series of 62 cases from 1970 described two cases in the scalp. [2] Enzinger would subsequently expand his findings with Chase in a larger series of 241 cases published in 1985, which included one more case from the ear [5]. ES of the ear has also been reported by Nayak et al. [9]. In addition, ES has been described around the ear (supra-auricular, pre-auricular and post-auricular locations), nose, hard palate, pharynx, tongue, gingiva, neck, cervical spine, retro-orbital area, orbit, nasal cavity, and temporal space [7, 26–38]. Apart from primary ES, metastatic ES has also been reported in the head and neck region, including metastases to the tongue and scalp [6, 8, 39, 40].

When ES occurs in the head and neck region, it may be easily confused with a poorly differentiated carcinoma [31]. This is in part due to the morphological mimicry of ES, a point highlighted even in the initial series by Enzinger [2]. Another factor adding to this confusion is the expression of cytokeratin (CK) and epithelial membrane antigen (EMA) in ES [3, 25, 41, 42]. Furthermore, sarcomas in general, and ES in particular, are much less frequent in the head and neck region than carcinomas [43–46].

Apart from epithelial markers such as CK and EMA, ES may also express vascular endothelial markers, such as CD34, ERG, FLI1, and much less frequently, CD31 [4, 42, 47–50]. Approximately half of ES express CD34 [42, 51]. In a series by Stockman et al., 68% of ES expressed ERG while 93% of ES expressed FLI1 [4]. In another series by Miettinen et al., 40% of ES expressed ERG. Significant (distinctive membrane staining pattern) expression of CD31 in ES is rare but has been reported [42, 47]. Both ES and epithelioid vascular tumors may express CK and endothelial markers, possibly leading to diagnostic confusion between the two. Interestingly, there is a type of hemangioendothelioma (pseudomyogenic/epithelioid sarcoma-like hemangioendothelioma) which has historically been confused with ES [52–54]. Epithelioid vascular tumors show retained expression with INI1, unlike ES [41, 52].

In this case, our main diagnostic considerations were between ES and spindle cell carcinoma. The absence of overlying squamous dysplasia, absence of p63 expression in the tumor cells, patchy expression with CD34 and loss of INI1 expression in the tumor cells strongly argue against spindle cell carcinoma. While CD34 expression is present in approximately half of ES, in contrast less than 2% of carcinomas express CD34 [13, 42, 55, 56]. CD34 expression, when positive, is thus a useful discriminant between ES and carcinoma. P63 is one of the more sensitive IHC markers for spindle cell carcinoma [57, 58].

While lymph node metastasis from sarcoma is generally rare, lymph node metastasis is more common in certain histological types of sarcoma, such as ES, clear cell sarcoma, angiosarcoma and rhabdomyosarcoma [59, 60]. In a large series of 10,731 sarcoma cases, only 223 patients (2.1%) had lymph node metastasis. In this series, clear cell sarcoma, angiosarcoma, rhabdomyosarcoma and ES together accounted for 56 of the 223 cases of lymph node metastasis (25.1%) [60]. In another recent series of 52 ES cases, distant metastasis occurred in 30 patients. In this series, distant metastasis occurred most frequently to the lung (19 patients, 37%), followed by the lymph nodes (11 patients, 21%). 5 patients from this series had both lung and lymph node metastasis [12]. Although there was no histological confirmation of lymph node metastasis for our case, the CT imaging findings (multiple enlarged left level II enlarged lymph nodes, with possible central necrosis within the largest lymph node) would be very suspicious for lymph node metastasis.

The predominant predictor of outcome in ES is histologic subtype, with proximal-type ES (10 year overall survival estimate of 37%) conferring a worse prognosis than classic ES (10 year overall survival estimate of 54%) [12]. Other adverse prognostic factors include proximal site, large size, male gender, older age, tumor depth and inadequate excision [3].

In summary, we present a rare case of epithelioid sarcoma arising from the left EAC. The neoplastic cells widely expressed pan-cytokeratins (AE1/3 and CAM5.2), and were patchily positive for ERG and CD34. The tumor cells exhibited complete loss of nuclear INI-1 expression. Awareness that ES may rarely arise at unusual sites is of critical importance in order to apply a broad enough panel in the immunohistochemical study, so a misdiagnosis of carcinoma can be avoided.

Funding

No funding was received.

Compliance with Ethical Standards

Conflict of interest

The authors have no conflict of interest.

Ethical Approval

It is our institution’s policy not to require formal ethical approval for reports on up to two patients.