Pigmented epithelioid melanocytoma: Two case reports1. Central Coast Dermatology, Inc., Santa Maria, California 2+3. Western Dermatopathology Services, San Luis Obispo, California
Bruce Howard MD1, Bruce Ragsdale MD2, and Kurt Lundquist MD3
Dermatology Online Journal 11 (2): 1
Because of indolent course without mortality, the term "pigmented epithelioid melanocytoma" has been suggested as a replacement for "equine" or "animal-type" melanoma and for the epithelioid blue nevus of the Carney type, from which they are histologically indistinguishable. This report reviews this concept and recounts in detail two of eighteen cases occurring in residents of the Central Coast of California. This paper also contains clinical photographs of pigmented epithelioid melanocytoma, unlike prior reports.
Rare, heavily pigmented melanocytic tumors with an indolent but sometimes aggressive behavior, and with clinical/histological similarities to equine melanotic disease and to melanomas arising in laboratory animals have been reported in the literature as "animal type" melanoma . The concept of "animal type" melanomas was not widely accepted because there were no large series of the entity, and because definitive histologic criteria were not developed. In 2004, a clinicopathologic analysis of 41 cases found no aggressive behavior and the authors recommended a term other than "melanoma," specifically pigmented epithelioid melanocytoma (PEM) . These tumors were compared with the original series of epithelioid blue nevus from patients with the Carney complex  from which they proved histologically indistinguishable. The study found that pigmented epithelioid melanocytoma has a predilection for children, adolescents, and young adults, occurring over a broad age range. No ethnic predominance was claimed, though their table I indicates that of 36 patients, 8 were hispanic and 4 black. It was thought that sun exposure was unlikely to be a major factor in pathogenesis. Lymph node metastases were detected in 46% of the patients who underwent sentinel node biopsy. Liver metastasis occurred in a single patient who has continued to do well two years after resection of the metastasis. There were no tumor-reported deaths in that series. Additional cases of animal-type melanoma with a positive sentinel node biopsy have been reported. [5,6].
Report of Cases
A 27-year-old white male sought medical advice for an enlarging pigmented lesion on the vertex of the skull, which had been present for approximately ten years. He stated that a "cancerous mole" had been removed when he was six years of age, the medical records and slides of which are no longer available.
|Figure 1||Figure 2|
The lesion at presentation was a 5mm. diameter smooth, blue-black papule with protruding hairs (Fig. 1). The clinical impression was benign combined nevus.
|Figure 3||Figure 4|
Histologically, the dome shape of the clinical lesion (Fig. 2) was due to dermal distention by very heavily melanized rounded cells resembling melanophages, save for somewhat larger nuclei with prominent nucleoli (Fig. 3). Less pigmented epithelioid and spindle shaped melanocytes were admixed. A junctional component was scant and less atypical, consistent with antecedent nevus. No conspicuous Pagetoid pattern in epidermis was evident (Fig. 4).
The provisional biopsy diagnosis was "atypical melanocytic lesion: blue nevus variant vs. malignant melanoma, 'animal type', pathological melanocytes extending to the dermal edges, but not to the peripheral epidermal biopsy margins." External consultation with Martin C. Mihm, Jr., M.D., Senior Dermatopatholgist, Massachusetts General Hospital, was motivated by "the inability to find a single mitotic figure".
Since Dr. Mihm's consultation was reported in 1999 before the PEM concept, his final diagnosis was "pigment synthesizing (animal/equine type) malignant melanoma," invasive at least to level IV and a measured depth of 2.2 mm., arising in a preexisting junctional nevus. Dr. Mihm commented that this rare variant of malignant melanoma "is identifiable by the large cells with prominent nucleoli that are consistently present throughout the lesion. The densely pigmented cells were noted to have similar nuclear characteristics allowing one to separate them from macrophages. There was no maturation as the cellular infiltrate of epithelioid and spindle cells extended to the base of the biopsy specimen".
Dr. Mihm further indicated that the scalp is one of the more characteristic locations of these lesions and that many of these lesions are present for many years, with or without evidence of a pre-existing nevus.
The patient underwent re-excision with 2 cm. margins, followed by lymphatic mapping using technetium sulphur colloid. A right modified radical posterior neck dissection found that one of thirteen lymph nodes contained a focal cluster of S-100 and HMB-45 positive cells in the subcapsular sinus. CAT scans of the chest, abdomen and pelvis performed at the time of surgery showed no abnormality.
After the surgical sites were healed, the patient received a course of radiation therapy with a 6 MeV linear accelerator to the right cervical lymphatic chain. Concurrently, he received a course of intravenous alfa interferon therapy and has remained well for five years following treatment.
A 23-year-old female immigrant from Mexico presented with an enlarging pigmented lesion on the lateral aspect of the left ankle, which had been present for 12 years. She stated that the lesion had begun to "burn" in the previous week.
The 8 x 10 mm slightly verrucous lesion was uniformly grayish-brown (Fig. 5). The clinical impression was combined nevus.
|Figure 5||Figure 6|
Histologically a dense pigmented dermal infiltrate composed of densely pigmented melanocytes and admixed melanophages elevate a hyperplastic, hyperkeratotic epidermis and descend to the deep biopsy surface at 2.3 mm thickness, at least Clark level IV (Fig. 6). A bleached section and a well-controlled HMB-45 immunohistochemical stain confirmed that the majority of the cells are epithelioid melanocytes with large nucleoli (Fig. 7, H + E).
This case was similarly reviewed by Dr. Martin Mihm, who agreed with the provisional diagnosis of PEM present at the margin. His advice was re-excision of the lesion with at least a 0.5 to 1 cm. margin and sentinel lymph node sampling. The biopsy site was re-excised with a 1cm. margin to the depth of the underlying fascia without finding residual tumor. No node sampling occurred.
Equine/animal type melanoma was first described in 1832 in old gray horses, consisting of nodules of heavily pigmented cells . Equine melanotic disease predominately affects the perineum, vulva or penile sheath, the undersurface of the tail, the mammary glands, the inner surface of the lip, and the external auditory meatus. Although largely indolent, metastatic deposits have been found in the spleen, liver, bone marrow and parotid gland .
The differential diagnosis for PEM includes melanocytic lesions characterized by both hypercellularity and prominent melanin synthesis, specifically cellular blue nevus, malignant blue nevus, deep penetrating nevus, plexiform spindle nevus, pigmented spindle and epithelioid cell (Spitz) nevus, malignant melanoma arising in nevi of Ito and Ota and regressed melanoma with prominent melanophages (tumoral melanosis)..
In our local region on the California Central Coast, Western Dermatopathology Services has had experience with seventeen tumors demonstrating features of PEM in patients ranging in age from 6 to 52. Most of these patients are included in reference 3 because consultation was obtained from Dr. Mihm. The local seventeen patients were comprised of 11 females and 7 males. Approximately half of the patients were Latino and two were African-American. The lesions were located on the legs (3), feet (3), buttocks (2), back (2), scalp (2) and arms (2). Ranging in size from 2 to 10 mm, most of the lesions were Clark level IV, with thicknesses from 1.1 to 4.1 mm. Nine of these patients had sentinel node biopsies, and in two instances, the nodes contained subcaspsular lesional melanocytes. In one of the patients pigmented cells were present in the capsule and fibrous septae and had the appearance of a nodal nevus. None of the patients have had local recurrence or progression of disease.
The significance of heavily pigmented melanocytes in lymph nodes is controversial. There are numerous case reports of darkly pigmented dendritic and bipolar nevus cells admixed with melanophages in small portions of the lymph node capsules, perinodal fibroadipose and intranodal fibrous trabeculae [15-18]. These nodal nevi were incidentally found in lymph nodes removed for other reasons. Darkly pigmented melanocytes have also been described within the parenchyma or subcapsular sinuses of regional lymph nodes associated with benign cellular blue nevi [15-18]. Recent studies of problematic Spitzoid melanocytic lesions have found positive sentinel lymph nodes in (44%-50%) of cases, a rate similar to that reported in PEM .
The histogenesis of these intranodal melanocytic deposits may be a melanocyte migration arrest, a benign metastasis, or sine qua non evidence of metastatic melanoma. In Dr Su's study of problematic Spitzoid melanocytic lesions more than 1.2 mm thick , the cases with positive sentinel lymph nodes were reclassified as malignant melanomas. His opinion is supported by the presence of melanoma like cytogenetic abnormalities in small numbers of atypical Spitz tumors and reported cases of problematic Spitz nevi which disseminated with lethal outcome [19-21].
Cytogenetic studies of PEM along with additional follow-up may confirm provide further insight into PEM. We are evaluating our cases with comparative genomic hybridization to see if they share any chromosomal abnormalities with melanomas or Spitz nevi. It would be interesting to compare the positive sentinel lymph node rate in classic Spitz nevi, blue nevi, and PEM.
Subsequently our material has indicated that the histopathologic pattern now designated as PEM may comprise part of a lesion that is otherwise a conventional compound melanocytic nevus. In addition, superficial spreading melanoma and lentigo maligna melanoma may exhibit features of pigmented epithelioid melanocytoma in their vertical growth phase. These "combined" cases are not included among the seventeen pure PEM lesions briefly discussed above.
Thus far, PEM has shown only anecdotal ability to spread beyond local lymph nodes, as well as a low risk of local recurrence, the conclusion being that it is a low-grade melanocytic tumor. However, longer follow up will be needed to establish a definitive prognosis for pigmented epithelioid melanocytoma. Dr. Mihm recommends sentinel lymph sampling and conservative re-excision in the management of these cases as a diagnostic procedure with the goal of better defining the biologic potential of these tumors.
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