Pigmented epithelioid melanocytoma: two case reports

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.     

Pigmented epithelioid melanocytoma: Report of a case and review of 173 cases in the literature

Pigmented epithelioid melanocytoma (PEM), or animal-type melanoma, is an unusual variant of melanoma which has been reported to have indolent behavior and a relatively good prognosis. We report a 12-year-old girl with PEM on the third finger web of her right hand. Histopathologically, it was composed of heavily pigmented dermal epithelioid and spindled melanocytic tumor cells. A sentinel lymph node biopsy was negative, and no recurrence was noted 1 year later. We reviewed 173 previously published cases of PEM or so-called animal-type melanoma in the literature. Among the 173 cases and our case, extremities were the most common sites of occurrence (52/129, 40.3%), and most of the depth of invasions were Clark level IV and V [76/114 (66.7%) and 33/114 (28.9%), respectively]. Lymph nodes metastasis was noted in 39/89 (43.8%) of the cases being investigated. Only two cases died of the disease with visceral metastasis. Thus, a more advanced level of invasion and the presence of lymph node metastasis did not imply a definitely malignant clinical course, because spreading beyond lymph nodes was rare (5/174, 2.9%). However, long-term follow-up with more cases and further research are needed to fully delineate the true biological nature of this pigmented melanocytic tumor.     

Cellular blue nevus with atypia (atypical cellular blue nevus): a clinicopathologic study of nine cases

Atypical cellular blue nevus (ACBN) has clinicopathologic features intermediate between typical cellular blue nevus (CBN) and the rare malignant blue nevus (MBN)/malignant melanoma (MM) arising in a CBN. Herein we report 9 cases of ACBN. The patients were caucasian (6 females and 3 males) with a mean and median age of 47/51 years. Two patients complained of recent changes and about half of these tumors were located on the buttocks or scalp, averaging 1.5 cm in diameter. Histologically, they were characterized by architectural atypia (infiltrative margin and/or asymmetry) and/or cytologic atypia (hypercellularity, nuclear pleomorphism, hyperchromasia, mitotic figures, and/or necrosis). Assessment of the expression of 3 tissue markers demonstrated rare solitary cell staining with oncogene product bcl-2, and a proliferative index of 23±19 and 39±30 cells/10 high power field with antibodies to PCNA and Mib-1, respectively. No significant differences were detected comparing the above levels of expression to a control group of 15 CBN; however, ACBNs tended to show a higher proliferative index by PCNA and Mib-1 as well as a significantly higher mitotic rate (1/10 HPF vs. 0; p=0.001). Analysis of DNA content showed DNA anetiploidy in both groups. Follow-up data on 9 of 9 patients showed 1 patient dead without disease and 8 alive without disease (mean/median follow-up 42/32 months, range 15-96 months). No patient during this follow-up time has experienced either a local recurrence or lymph node or visceral metastasis. These findings highlight the close resemblance of ACBN to the natural history of CBN. Nevertheless, many of the distinguishing histologic features of ACBN are also those of MBN. Because of these intermediate clinicopathologic features, ACBN warrant close scrutiny and long-term follow-up.     

Pilonidal sinus associated with cellular blue nevus. A previously unrecognized association

A neoplasm associated with a pilonidal sinus (PS) is a rare occurrence in the course of a common disease. Early detection is imperative. To our knowledge, pilonidal disease associated with a cellular blue nevus (CBN) has not been reported. There is a 10% diagnostic error rate with this last lesion. Here we report the case of a 19-year-old man with recurrent sacrococcygeal PS infection associated with an indurated dome-shaped blue-black nodule 1.7 cm in diameter. Clinical diagnosis of the nodule was uncertain suggesting a pigmentary or a vascular tumor. A complete resection of the two lesions was achieved. Pathological study showed a CBN showing a predominantly alveolar pattern associated with a chronic pilonidal disease. The tumor cells showed diffuse strong reactivity for melan-A and HMB-45, and focal reactivity for S-100 protein. Staining for Ki-67 (MIB1) was virtually negative. Differential diagnoses included atypical CBN, borderline melanocytic tumor and malignant melanoma. Radical excision provides a good prognosis for the rare association consisting of a common disease such as PS with the uncommon CBN.     

Malignant blue nevus: a report of eight cases.

Malignant blue nevus is uncommon compared to its benign counterpart and is regarded as a rare form of malignant melanoma. We report the clinical and histological findings in eight cases. Histologically, all eight specimens showed no epidermal involvement and had contained within or were adjacent to portions of blue nevus or cellular blue nevus. Proliferation of bundles of bipolar spindle shaped cells with marked cellular atypia, mitotic figures, foci of necrosis, and inflammatory cell infiltrate were noted. Two of the cases were studied by DNA flow cytometry and the populations of tumor cells were found to be diploid. Two cases have died secondary to metastasis. Although malignant blue nevi may not behave as aggressively as nodular malignant melanoma, they have definite potential to do so and therefore should be removed by wide surgical excision.     

Melanoma ex blue nevus: two cases resembling large plaque‐type blue nevus with subcutaneous cellular nodules

Large plaque‐type blue nevi with subcutaneous cellular nodules are rare tumors occurring on the trunk with deep extension into underlying soft tissues. The histopathologic appearance consists of deep nodules resembling cellular blue nevi with interspersed foci of common blue nevus. Conservative management has been recommended, and metastases have not been observed. This report discusses two cases with microscopic features of large plaque‐type blue nevi with subcutaneous cellular nodules in which comparative genomic hybridization showed chromosomal aberrations typical of melanoma. In both cases, the nodules showed gains involving chromosome 6p and losses involving chromosome 6q, which are among the most commonly found aberrations in melanoma. These copy number changes were not present in the less cellular surrounding areas that appeared characteristic of blue nevus. These cases illustrate that large blue nevi with a deep, multi‐nodular configuration should be interpreted with caution, and that superficial biopsies of such lesions can be misleading. Molecular techniques can provide valuable insights in these types of difficult melanocytic neoplasms.     

Benign and malignant cellular blue nevus. A clinicopathological study of 30 cases

The clinical and pathological features of 29 cellular blue nevi (CBN) and one malignant cellular blue nevus from our hospital files were reviewed. Although the sacrococcygeal region/buttock was the commonest single site, the majority of CBN occurred on the limb peripheries. Two-thirds of patients were under the age of 40 years. Follow-up of a mean of 7 years did not reveal any evidence of malignancy. Four histological subtypes were recognized: mixed biphasic, alveolar, fascicular or neuronevoid, and atypical varieties. One case developed a benign nodal metastasis. In one case, malignancy arose within a CBN. The importance of recognizing the variety of patterns, the benign behavior of the atypical variety, and the criteria for malignancy are herein discussed.     

Malignant blue nevus: case report of a Japanese man with a distant cutaneous metastasis

We report a 55-year-old Japanese patient with a malignant blue nevus (MBN) on the scalp. The patient had regional lymph nodes metastases at his first visit, and a distant cutaneous metastatic papule appeared on the back 1 year later despite therapeutic intervention. Histology of the primary tumor lacked a junctional component and showed a typically biphasic pattern in the degree of pigmentation similar to a cellular blue nevus (BN). One pattern showed nests of less-pigmented, oval-shaped cells with a fairly uniform appearance, and the other pattern showed an aggregation of spindle-shaped cells containing a large amount of melanin pigment intermingled with heavily pigmented melanophages. Histology of metastatic regional lymph nodes also showed a biphasic proliferative pattern of oval-shaped, pale cells and spindle-shaped, richly pigmented cells. A distant cutaneous metastatic papule on the back showed massive proliferation of atypically large, pale, and oval-shaped melanoma cells with heavily pigmented melanophages just beneath the uninvolved epidermis. These histologic features were different from those of metastatic tumor proliferation from conventional melanoma. It seems probable that MBN might maintain a different biological and histopathologic character from conventional melanoma when it grows in metastatic sites.     

皮损形态类似于脂溢性角化病的普通型蓝痣一例

蓝痣的临床表现多种多样,临床上最常见的为普通蓝痣和细胞蓝痣。此外,还有一些特殊的类型,如无色素性蓝痣、上皮样蓝痣和斑块型蓝痣等。本文报道一例皮损的临床表现类似于脂溢性角化症的普通型蓝痣。     

Intraoral cellular blue nevus: report of a unique histopathologic entity and review of the literature

The blue nevus is found most frequently on the skin; however, in rare instances, it has been reported on oral mucous membranes. Intramucosal nevi make up more than one half of all reported intraoral melanocytic nevi. The common blue nevus is the second most common variant. Among the 3 variants of blue nevi, the cellular variant occurs less frequently than the common and combined variants. We present a rare case of intraoral cellular blue nevus that occurred on the oral mucosa of the hard palate. Because of the clinical and microscopic resemblance of the cellular blue nevus to melanoma and the rarity of this lesion in the oral cavity, recognition and accurate diagnosis are critical.     

Amelanotic blue nevus: a variant of blue nevus.

Blue nevi are typically heavily melanized. We report a variant of blue nevus that is minimally pigmented. Of the 1,358 blue nevi seen in our laboratory during the last 6 years, 38 (2.7%) were selected that had scant or absent melanin. We refer to these blue nevi as the amelanotic type. Approximately half of the cases in clinical diagnosis were nevus of some type, whereas other differential diagnoses were basal cell carcinoma, dermatofibroma, and lesion. Histologically all specimens were characterized by the spindle-shaped cells seen in blue nevi, but with very little or no obvious melanin. Some lesions were markedly cellular, resembling the features of cellular blue nevus. No hemosiderin was identified on Perls' stain, whereas Fontana-Masson stain was variably positive. Usually there was fibrous stroma. In most cases, the histologic differential diagnosis was dermatofibroma. Other histologic differential diagnoses included amelanotic and/or spindle cell melanoma, dermal Spitz nevus, neurofibroma, and scar. There was no pleomorphism or increased mitotic activity. Evidence of epidermal melanocytic hyperplasia was seen in two cases. Furthermore, the lesions had been present for many years without evidence of recent change. Immunohistochemistry showed all cases to be strongly positive with anti Mel-5 antibody, but only weakly positive or negative with anti S-100 and HMB-45 antibodies. We would like dermatologists and pathologists to be aware of this unusual and uncommon entity.     

A cellular blue nevus with pigmented epithelioid melanocytoma‐like pattern on the ipsilateral upper arm associated with a congenital plaque‐type blue nevus on the hand

A 36‐year‐old man presented with a subcutaneous nodule on the right upper arm. A small nodule had developed 8 years earlier, and grew in size, accompanied by a tingling sensation and numbness. In addition, he had a bluish irregular patch on the right hand since birth, which crossed from the palm to the dorsal hand. Skin biopsies from the hand showed a heavily pigmented melanocyte proliferation in the dermis with perieccrine, perivascular, and perineural involvement, and a diagnosis of congenital plaque‐type blue nevus was made. The tumor on the arm was located closely along the median nerve, and was observed as a large black pedunculated round tumor. Histopathologically, the tumor on the arm consisted of densely packed tissue with nevoid cells without atypia in the larger nodular part, and heavily pigmented spindle and epithelioid melanocytes in the slender stalk area, which was diagnosed as cellular blue nevus with pigmented epithelioid melanocytoma‐like pattern. Next‐generation sequencing revealed GNAQ mutations in the hand lesion, and in the lesions on the arm. This case suggests that the areas of skin following the same neural distribution of a congenital plaque‐type blue nevus on the extremities should be followed up for secondary changes.     

Malignant blue nevus: a case report and molecular analysis

Malignant blue nevus is a rare melanocytic tumor that is described by some authors as a variant of malignant melanoma, whereas others regard it as a distinct entity. To our knowledge no molecular studies of this tumor have been performed, although the molecular pathogenesis of conventional melanomas has been extensively described. We present a case of malignant blue nevus that developed in a 15-cm congenital blue nevus on the back of a 41-year-old man. Subsequent regional lymph node and lung metastases developed within 1 and 29 months, respectively. We performed a molecular analysis for loss of heterozygosity on microdissected samples from the spectrum of benign to malignant blue nevus, using a panel of eight genes (MTS1, MXI1, CMM1, p53, NF1, L-myc hOGG1, and MCC), many of which are commonly associated with conventional melanomas. No loss of heterozygosity was detected, despite informativeness in seven genes. We suggest that malignant blue nevus may represent a distinct entity with a different molecular pathway to tumorigenesis than that of conventional melanomas.