Journal of Pediatric Ophthalmology and Strabismus

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Short Subjects 

Pigmented Epithelioid Melanocytoid Tumor of the Ocular Adnexa

Jason A. Sokol, MD; Jeremy D. Clark, MD; Hui Bae Harold Lee, MD; William R. Nunery, MD

Abstract

An 8-year-old girl with a history of microphthalmia in the right eye presented with a left medial upper eyelid mass with a dark blue-green nodule that could be seen through the skin but did not appear to involve the overlying epidermis. A biopsy demonstrated a pigmented epithelioid melanocytoid tumor with rare mitoses arising in association with a congenital nevus and positive margins. Due to the pathological findings, the patient underwent excision of the tumor with 5-mm margins and a sentinel lymph node biopsy. The re-excision of the upper eyelid margins demonstrated residual benign congenital melanocytic nevus, but did not reveal residual melanocytic lesion. The parotid sentinel node biopsy revealed benign and cytologically mature nevus nests in the capsule and septa, but there was no evidence of involvement with the pigmented epithelioid melanocytoid tumor. The patient underwent successful eyelid reconstruction and had no evidence of recurrence or metastasis after 2 years.

Abstract

An 8-year-old girl with a history of microphthalmia in the right eye presented with a left medial upper eyelid mass with a dark blue-green nodule that could be seen through the skin but did not appear to involve the overlying epidermis. A biopsy demonstrated a pigmented epithelioid melanocytoid tumor with rare mitoses arising in association with a congenital nevus and positive margins. Due to the pathological findings, the patient underwent excision of the tumor with 5-mm margins and a sentinel lymph node biopsy. The re-excision of the upper eyelid margins demonstrated residual benign congenital melanocytic nevus, but did not reveal residual melanocytic lesion. The parotid sentinel node biopsy revealed benign and cytologically mature nevus nests in the capsule and septa, but there was no evidence of involvement with the pigmented epithelioid melanocytoid tumor. The patient underwent successful eyelid reconstruction and had no evidence of recurrence or metastasis after 2 years.

From the Department of Ophthalmology and Visual Sciences (JDC, HBHL, WRN), Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky; Oculofacial Plastics and Orbital Surgery (HBHL, WRN), Indiana University, Indianapolis, Indiana; and Oculofacial Plastic and Orbital Surgery (JAS), Kansas University Eye Center, Kansas University Medical Center, Kansas City, Kansas.

Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York.

The authors have no financial or proprietary interest in the materials presented herein.

The authors thank Matthew Kuhar, MD, and Simon J. Warren, MBBS, from the Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, Indiana.

Address correspondence to Jason A. Sokol, MD, Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, 301 E. Muhammad Ali Blvd., Louisville, KY 40202. E-mail: jsokolmd@gmail.com

Received: April 16, 2010
Accepted: September 01, 2010
Posted Online: October 21, 2010

Introduction

Animal-type melanoma is a rare melanocytic lesion that was first described in gray horses by Dick in 1832.1 Later, Darier compared animal-type melanomas to a similar lesion in humans that he called “melanotic sarcoma.”2 Further observations on lesions called “equine-type” melanomas were published in the second half of the 20th century.3 There is still a debate about the appropriate name for these pigmented lesions. In this report, we will refer to the specimen as pigment epithelioid melanocytoid tumor (PEMT).

In Zembowicz et al.’s series,4,5 the presence of ulceration was the only histological factor that reliably differentiated animal-type melanoma from epithelioid blue nevus. Given the histological overlap and to avoid designating controversial lesions as either nevus or melanoma, Zembowicz et al. suggested the term pigmented epithelioid melanocytoma for “animal-type melanoma” and for epithelioid blue nevus occurring in patients with the multiple neoplasia syndrome Carney complex.4,5 Pigmented epithelioid melanocytoma is not accepted as the universal nomenclature. Antony et al. suggested the term “pigment synthesizing melanoma” should be used, noting that pigmented epithelioid melanocytoma implies a more benign tumor and might be misleading or confusing.6

Pigmented epithelioid melanocytoid tumor was the term chosen for this report because it avoids the term “melanocytoma,” which implies a benign lesion, and also avoids the term “melanoma,” which is a serious diagnosis for a young patient to carry throughout life and may cause socioeconomic hardship (ie, insurance procurement). PEMT tends to occur in children, adolescents, and young adults, but occurs in a broad age range. We present the first case of ocular adnexal PEMT in a young monocular child with a negative sentinel lymph node for PEMT.

Case Report

An 8-year-old girl with a history of microphthalmia in the right eye presented with a left medial upper eyelid mass, which had grown over a 2-month period. The remainder of the patient’s medical history and family history was unremarkable. On examination, the patient’s visual acuity was no light perception in the right eye and 20/30+3 in the left eye. A prosthesis was in good position over her microphthalmic right eye. External examination was significant for a left medial upper eyelid mass with a dark blue-green nodule that could be seen through the skin but did not appear to include the overlying epidermis (Fig. 1). Clinically, the lesion appeared firm and vascular with a thrombus. No pulsations were present on palpation. The remainder of the examination was unremarkable. Systemic investigation included computed tomography scans of the brain, chest, abdomen, and pelvis, which were all negative for metastatic disease.

(A) Preoperative Photograph of Initial Pigmented Lesion. (B) Intraoperative Photograph from First Excisional Biopsy. (C) Preoperative Photograph of Non-Discrete Pigmentation Around the Original Biopsy Prior to the Re-Excision. (D) Intraoperative Photograph of the Re-Excision.

Figure 1. (A) Preoperative Photograph of Initial Pigmented Lesion. (B) Intraoperative Photograph from First Excisional Biopsy. (C) Preoperative Photograph of Non-Discrete Pigmentation Around the Original Biopsy Prior to the Re-Excision. (D) Intraoperative Photograph of the Re-Excision.

The patient underwent a surgical excision of the lesion. The biopsy demonstrated an expansile but well-circumscribed sheet-like dermal nodule of heavily pigmented and atypical epithelioid melanocytes arising adjacent to a benign congenital nevus composed of small, spindled benal melanocytes. The atypical melanocytes had prominent nucleoli and rare mitoses, but were relatively monotonous. Atypical melanocytes and congenital nevus cells were present at the margins of the surgical excision specimen (Fig. 2). Of note, the patient developed non-discrete pigmentation around the original biopsy site in the 3-week period between the first and second surgery (Fig. 1). Clinically, we are not sure whether this new pigmentation represents post-inflammatory changes or a residual melanocytic proliferation.

(A) Low-Power View (hematoxylin–Eosin, Original Magnification ×40) of the Well-Circumscribed and Heavily Pigmented Expansile Nodule. (B) Moderate-Power View (hematoxylin–Eosin, Original Magnification ×100) of Interface Between the Atypical Cells of the Melanocytic Lesion and the Small Spindled Melanocytes of the Adjacent Congenital Nevus (arrows Indicate Areas of Interface). (C) High-Power View (hematoxylin–Eosin, Original Magnification ×400) of the Sheeted Melanocytes in the Pigmented Epithelioid Melanocytoid Tumor with Prominent Nucleoli, Heavy Melanin Pigmentation, and Relative Monotony.

Figure 2. (A) Low-Power View (hematoxylin–Eosin, Original Magnification ×40) of the Well-Circumscribed and Heavily Pigmented Expansile Nodule. (B) Moderate-Power View (hematoxylin–Eosin, Original Magnification ×100) of Interface Between the Atypical Cells of the Melanocytic Lesion and the Small Spindled Melanocytes of the Adjacent Congenital Nevus (arrows Indicate Areas of Interface). (C) High-Power View (hematoxylin–Eosin, Original Magnification ×400) of the Sheeted Melanocytes in the Pigmented Epithelioid Melanocytoid Tumor with Prominent Nucleoli, Heavy Melanin Pigmentation, and Relative Monotony.

Due to the pathological findings of positive tumor margins and the rendering of a diagnosis of PEMT, the patient underwent re-excision of the tumor with 5-mm margins. Earlier computed tomography of the brain showed no regional adenopathy, so sentinel lymph node biopsy was performed. The re-excision of the upper eyelid margins demonstrated residual congenital melanocytic nevus. The parotid sentinel lymph node biopsy revealed benign nevus nests encased in a capsular membrane. The parotid septa lesion demonstrated a benign nevus nest in a paraseptal array. There was no evidence of residual PEMT in the sentinel node or eyelid. The patient underwent successful eyelid reconstruction and was without evidence of recurrence of metastasis after 2 years.

Discussion

The first description of equine or animal-type melanoma was recorded in 1832, when nodules of heavily pigmented cells occurred in old gray horses.1 The sites predominantly affected by equine melanotic disease include 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. Metastasis in this indolent tumor has been found in the spleen, liver, bone marrow, and parotid gland.7

PEMT occurs in both high-risk melanoma populations such as whites and low-risk melanoma populations such as Hispanics, Asians, Persians, and African Americans.4,5 PEMT clinically presents with a dark bluish dermal nodule with or without ulceration or dermal hyperplasia.5 Due to the high incidence of metastasis to sentinel nodes (46% in the Zembowicz et al. series4), PEMT is considered a low-grade melanoma or melanocytic tumor with a good prognosis.5 PEMT has a tendency to recur locally with satellite nodules and can spread to regional lymph nodes. Distant metastasis in PEMT is rare and has a better prognosis than metastatic melanoma.

Zembowicz et al. reported a series of 41 cases of PEMT that were histologically indistinguishable from epithelioid blue nevus of Carney complex.4 Despite epithelioid blue nevus’s association with Carney complex, it can also occur sporadically. Carney complex includes several low-grade or benign neoplasms, such as cutaneous and internal organ myxomas, large cell calcifying Sertoli cell tumor of the testis, osteochondromyxoma of the bone, and follicular neoplasms of the thyroid.4

Zembowicz et al. classified animal-type melanoma as pigmented epithelioid melanocytoma. Due to the wide site distribution, the report concluded that sun exposure was an unlikely factor in pathogenesis.4,7 The presence of tumor cells in the subcapsular space or lymph node parenchyma was required to interpret a positive sentinel node. Lymph node metastases were detected in 11 of the 24 patients (46%) who underwent a sentinel node biopsy. Those 11 cases underwent a supplementary regional completion lymphadenectomy. Five of the 11 patients had additional lymph node metastasis. One patient with a congenital PEMT, who presented with liver metastasis, continued to do well 2 years after resection of the metastasis. No tumor deaths were reported in this series. Sixty-seven percent of the reported cases had at least 1 year of follow-up and none of the patients developed recurrence at the excisional biopsy site.4,8

Histologically, PEMTs are melanocytic neoplasms that display intense cytoplasmic melanin pigmentation with infiltrative margins. They are composed of a blend of intensely pigmented spindle cells and epithelioid cells. If present, mitoses are rare and do not exceed 3 units/mm2. However, there is some evidence that those with more malignant cytology may be more aggressive.3 Zembowicz et al. discovered no correlation between the presence of ulceration, the degree of cytologic atypia or mitotic activity, and the finding of lymph node metastasis.5 Metastases occurred in lesions with no mitotic activity and bland cytologic features. PEMT has a large differential diagnosis including malignant melanoma arising in nevi of Ito and Ota, regressed melanoma with prominent melanophages, cellular blue nevus, deep penetrating nevus, plexiform spindle nevus, pigmented spindle malignant blue nevus, and epithelioid cell (Spitz) nevus.7 Occasionally, PEMT is associated with congenital or dermal nevus, but regularly arises de novo.5

Despite the frequency of PEMT spreading to local lymph nodes, this tumor has shown limited ability for distant metastasis or local recurrence.4,8 This unique feature will challenge the prognostic importance of sentinel lymph node positivity in borderline melanocytic lesions such as PEMT and perhaps “benign” metastasizing Spitz nevi9 and spitzoid “nevoid” melanomas.10 The current recommendation for sentinel lymphadenectomy in PEMT is still unsettled. However, one may consider sentinel lymphadenectomy in all patients with non-Carney complex tumors greater than 1 mm in depth or 0.75 to 1 mm with other adverse features such as ulceration or a high mitotic rate. In cases of a positive sentinel lymph node, complete lymphadenectomy may be considered. There are no recommendations for systemic therapy at this time, because PEMT-related deaths from metastasis have not been reported.4,8

References

  1. Dick W. Melanosis in men and horses (letter). Lancet. 1832:192.
  2. Darier J. Le melanome malin mesenchymateau ou melanosarcome. Bull Assoc Fr Cancer. 1925;14:221–249.
  3. Vezzoni GM, Martini L, Ricci C. A case of animal-type melanoma (or pigmented epithelioid melanocytoid tumor?): an open prognosis. Dermatol Surg. 2008;34:105–109. doi:10.1111/j.1524-4725.2007.34023.x [CrossRef]
  4. Zembowicz A, Carney JA, Mihm MC. Pigmented epithelioid melanocytoma: a low-grade melanocytic tumor with metastatic potential indistinguishable from animal-type melanoma and epithelioid blue nevus. Am J Surg Pathol. 2004;28:31–40. doi:10.1097/00000478-200401000-00002 [CrossRef]
  5. Zembowicz A, Knoepp SM, Bei T, et al. Loss of expression of protein kinase a regulatory subunit 1alpha in pigmented epithelioid melanocytoid tumor but not in melanoma or other melanocytic lesions. Am J Surg Pathol. 2007;31:1764–1775. doi:10.1097/PAS.0b013e318057faa7 [CrossRef]
  6. Antony FC, Sanclemente G, Shaikh H, Trelles AS, Calonje E. Pigment epithelioid melanocytoma (so-called animal type melanoma): a clinicopathological study of 14 cases of a poorly known distinctive variant of melanoma. Histopathology. 2006;48:754–762. doi:10.1111/j.1365-2559.2006.02411.x [CrossRef]
  7. Howard B, Ragsdale B, Lundquist K. Pigmented epithelioid melanocytoma: two case reports. Dermatol Online J. 2005;11(2):1.
  8. Ward JR, Brady SP, Tada H, Levin NA. Pigmented epithelioid melanocytoid tumor. Int J Dermatol. 2006;45:1403–1405. doi:10.1111/j.1365-4632.2006.02883.x [CrossRef]
  9. Smith KJ, Barrett TL, Skelton HG, Lupton GP, Graham JH. Spindle cell and epithelioid cell nevi with atypia and metastasis (malignant Spitz nevus). Am J Surg Pathol. 1989;13:931–939. doi:10.1097/00000478-198911000-00003 [CrossRef]
  10. Wong TY, Suster S, Duncan LM, Mihm MC Jr, . Nevoid melanoma: a clinicopathological study of seven cases of malignant melanoma mimicking spindle and epithelioid cell nevus and verrucous dermal nevus. Hum Pathol. 1995;26:171–179. doi:10.1016/0046-8177(95)90034-9 [CrossRef]
Authors

From the Department of Ophthalmology and Visual Sciences (JDC, HBHL, WRN), Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky; Oculofacial Plastics and Orbital Surgery (HBHL, WRN), Indiana University, Indianapolis, Indiana; and Oculofacial Plastic and Orbital Surgery (JAS), Kansas University Eye Center, Kansas University Medical Center, Kansas City, Kansas.

Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Jason A. Sokol, MD, Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, 301 E. Muhammad Ali Blvd., Louisville, KY 40202. E-mail: jsokolmd@gmail.com

10.3928/01913913-20101018-07

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