Multifocal Pseudomyogenic Hemangioendothelioma Involving the Scalp and Nose, Misdiagnosed as A Sarcoma: A Rare Case Report

This case report aims to present clinicopathological features of an extremely rare case of multifocal pseudomyogenic hemangioendothelioma (PMHE) in the scalp. A 21-year-old male developed multiple, focally ulcerated, nodules over the root of his nose and scalp. One of the skin lesions was sampled at another dermatology clinic, where this was diagnosed as a sarcoma. A review of biopsy sections showed well-circumscribed dermal lesions, comprising plump spindle and epithelioid cells, mimicking rhabdomyoblasts. Immunohistochemically, tumor cells were positive for AE1/AE3, CD31, FLI-1 and ERG. INI-1 was retained. A diagnosis of PMHE was offered. Subsequently, the patient underwent wide excision and has been asymptomatic for 8 months, post-surgery. PMHE is rarely reported in the head and neck region, where it can constitute a diagnostic pitfall. Awareness of this tumor and appropriate immunohistochemical stains are necessary for its timely diagnosis, in order to avoid radical treatments. A review of similar, previously documented cases is presented.


CASE REPORT
A 21-year-old male presented to a dermatologist with multiple nodular lesions involving the skin of his scalp, forehead, and root of the nose of 4 months duration. He underwent a biopsy from the lesion over his nose which, at two different laboratories, was reported as high-grade sarcoma and leiomyosarcoma, respectively.
Thereafter, he was referred to us. During clinical evaluation, he seemed to be in good general health. During local examination, there were multiple, painless, nodular, fleshy lesions involving the skin of his scalp, forehead, and nose ( Figure 1A). A clinical diagnosis of cutaneous sarcoma was considered. He underwent radiological evaluation and the slides and paraffin blocks of his nasal lesion were reviewed.
Positron emission tomography (PET) scan showed multiple FDG-avid lesions involving the nasal root, and the frontal and left parietal region, the largest measuring 12 mm x 7.9 mm (SUVmax = 7.02) ( Figure 1B, C). A wide local excision of the lesions, followed by a reconstruction with a free flap was undertaken.
During review, the tumor sections were tested for various immunohistochemical antibody markers on an automated Ventana Benchmark XT ® platform.

Gross Findings
The resection specimens of the root of the nose and posterior scalp lesions were well-oriented, measuring 9 cm x 4.5 cm x 0.5cm and 8.5 cm x 5.5 cm x 0. 6 cm, respectively. Cut surfaces of both the specimens showed multiple greywhite, focally ulcerating, fleshy lesions.

Histopathological Findings
Microscopically, the biopsy revealed an infiltrating tumor, composed of spindle-shaped cells, involving the dermis and subcutaneous tissue.
Microscopic examination of the resection specimens revealed infiltrative, focally well-demarcated lesions, appearing as granulomas in lower magnification. The tumor cells were arranged in interlacing fascicles ( Figure  2A). On higher magnification, tumor cells were seen insinuating in between the adnexal structures and dermal nerves. Individual tumor cells were plump, spindle-shaped, containing moderate to abundant eosinophilic cytoplasm; central to eccentrically placed vesicular nuclei and discernible nucleoli, reminiscent of a "myoid" appearance. There were few bi-and multi-nucleate forms. Focal areas displayed "rhabdoid-like" cells, containing eccentrically placed crescentic nuclei and paranuclear eosinophilic inclusions. Additionally, there were pseudo-microcysts comprising cells with intracytoplasmic vacuoles. There were no significant mitotic figures and/or necrosis ( Figure  2A, B).

DISCUSSION
Multifocal pseudomyogenic hemangioendothelioma (PMHE) is characterized by young age, male predisposition, extremity location, multifocality and dermal location. Microscopically, it displays infiltrative borders and tumor cells resembling rhabdomyoblasts (3). Till date, only 12 cases of PMHE have been reported in the head and neck region, including 2 cases in the scalp, as noted in the present case (2-3, 5-9). Other reported uncommon sites include mucosal involvement in a single case and lymph node metastasis in 2 cases, of the head and neck region (Table I) (7)(8)(9).     Lack of overt vascular differentiation and a close resemblance, both clinically, as well as histologically, to other relatively commoner sarcomas, along with unawareness of this entity might mislead an unwary pathologist, as noted in the present case, which was misdiagnosed at two different laboratories.
In view of its overlapping features with other sarcomas, certain immunohistochemical antibody markers, including cytokeratins and vascular markers, along with INI1/SMARCB1 are essential for its diagnosis (3). A range of differential diagnoses have been considered in earlier reported cases, including an epithelioid sarcoma, rhabdomyosarcoma, epithelioid hemangioendothelioma, and sarcoma, not otherwise specified (NOS). The closest differential diagnosis in the present case was an epithelioid sarcoma, in view of a relatively superficial location, younger age and immunohistochemical expression of cytokeratin (6,8). However, a predominantly spindle cell morphology, along with immunopositivity for CD31 and retained expression of INI1, ruled out this possibility (3,(7)(8). Positivity for epithelial antibody markers and negative staining for skeletal muscle-specific markers, namely desmin, myogenin and MyoD1, ruled out a spindle cell rhabdomyosarcoma. It is noteworthy that most of the differential diagnoses of a PMHE are high-grade and relatively aggressive tumors.
Apart from its distinct morphological features and immunohistochemical profile, PMHE is characterized by a distinct molecular signature, in the form of a genetic fusion between FOSB (19q) with a strong promoter, SERPINE (7q22), ACTB(7p22), and recently WWTR1(3q25), all of which lead to an upregulation of FOSB expression (9)(10)(11). This led to development of FOSB immunostain for the diagnosis of PMHE (9). At the same time, FOSB is also expressed in epithelioid haemangiomas and in osteoblastomas. In view of unavailability, we could not test our case with FOSB. Nonetheless, unequivocal histopathological features supplemented with necessary immunohistochemical markers were supportive of a diagnosis of PMHE (Table II).
Contrary to some of its worrisome histopathological features, PMHE has an indolent clinical course with potential for local recurrence and a minimal risk of distant metastasis. Disseminated disease and metastasis has been reported in 6% of the cases (9). Development of metastasis after 5 years of the initial diagnosis, as previously reported, implies the need for a prolonged follow-up in such cases (3). The treatment is mainly aimed at wide excision of the lesions, instead of radical resections and adjuvant therapies, which are considered for its mimics such as an epithelioid sarcoma, malignant rhabdoid tumor and a spindle cell rhabdomyosarcoma. Adjuvant local radiotherapy has been offered in unresectable cases of PMHE. The present case was treated with wide-excision. The patient is alive with no evidence of disease, 8 months post-surgery.
In conclusion, PMHE is an uncommon, locally aggressive tumor of abstruse vascular origin, and an uncertain malignant potential affecting dermal and or subcutaneous tissue of various anatomical sites in young males. The head and neck, especially nose and scalp constitute its rare sites. With only 12 such reported cases in world literature, the present case, including its clinical impact, seemed worth reporting. Awareness of this entity, careful assessment of morphological features and certain immunohistochemical markers are necessary for its correct and timely diagnosis, in order to obviate unnecessary radical treatments, the latter reserved for recurrences or unresectable tumors, which in itself are exceedingly rare in these tumors.