Epithelioid Cell Nevus Research Articles

The Melanocytic Epithelioid Cell Nevus of the Thigh of Woman

The Melanocytic Epithelioid Cell Nevus of the Thigh of Woman

Spitz nevus and Reed nevus

Spitz and Reed nevi, also called spindle and/or epithelioid cell nevi, are a special group of melanocytic lesions due to their peculiar clinical, dermoscopic and histopathological features. The study of these nevi is of great interest because both their nomenclature and classification are still a matter of discussion. Most importantly, the difficulty to differentiate them from melanoma can lead to inadequate therapies. In this context, dermoscopy, a link between clinical and anatomopathological examinations, appears as a helpful diagnostic tool whose accuracy can reach 93%. "Borderline" lesions are still a great challenge and object of research, including molecular studies. The present study explores the relevant characteristics of these nevi, with emphasis on dermoscopic findings, aiming at understanding their natural history, as well as discussing treatment and patient follow-up.

Immunohistochemical Studies of Atypical Conjunctival Melanocytic Nevi

To evaluate with immunohistochemical methods 5 atypical melanocytic conjunctival lesions. This was a retrospective clinicoimmunopathologic study. Routine histochemical staining was performed with multiparametric immunohistochemical analysis with monoclonal antibodies immunoreacted on paraffin sections to identify the following cell antigens: S-100, MART-1, HMB-45, CD45, CD68, CD1a, lysozyme, and Ki-67 (nuclear proliferation protein). A unique granular cell nevus contained periodic acid-Schiff-positive, diastase-resistant granules and immunoreacted with monoclonal antibodies against S-100 protein and melanocytic-associated antigens MART-1 and HMB-45. Results for CD45, CD1a, CD68, and lysozyme immunostaining of the granular cells were negative. Two epithelioid cell (clonal or inverted) nevi exhibited an identical immunohistochemical profile. Only the balloon cell nevus was MART-1-positive and HMB-45-negative. The granular cell and blue nevi immunoreacted negligibly with Ki-67 (approximately 1% of cells). S100 and MART-1 reliably immunostained all nevocytic morphologic variants. HMB-45 immunoreactivity of the granular, epithelioid/clonal, and blue nevi did not indicate a more active or proliferative lesion but instead suggested abnormal melanogenesis. Ki-67 was the most valuable immunohistochemical adjunct to morphology for the diagnosis of these benign variant conjunctival nevi, because melanomas display a much higher proliferation index (>10% nuclear positivity among all cells counted) than the current nevi (approximately 1%).

TRPM1 (Melastatin-1/MLSN1) mRNA expression in Spitz nevi and nodular melanomas

The transient receptor potential cation channel, subfamily M, member 1 (TRPM1/Melastatin-1/MLSN-1) expression has been shown to have prognostic utility in the evaluation of primary cutaneous melanoma. We analyzed a series of spindled and epithelioid cell nevi (Spitz) and primary cutaneous nodular melanomas to determine whether the expression of TRPM1 mRNA may be useful in distinguishing between Spitz nevi and nodular melanomas and to further examine the patterns of TRPM1 mRNA expression in cutaneous melanocytic proliferations. Formalin-fixed, paraffin-embedded tissues from 95 Spitz nevi and 33 nodular melanomas were analyzed for the expression of TRPM1 mRNA by in situ hybridization using 35S-labeled riboprobes. Ubiquitous melanocytic expression of TRPM1 mRNA was observed in 56 of 95 (59%) Spitz nevi and 4 of 33 (12%) nodular melanomas. Diffusely scattered loss of TRPM1 mRNA was identified in 38 of 95 (40%) Spitz nevi and 2 of 33 (6%) nodular melanomas. Regional loss of the TRPM1 mRNA expression by a significant subset of dermal tumor cells or a complete absence of TRPM1 expression by the dermal tumor was identified in 27 of 33 (82%) nodular melanomas, but only 1 of 95 (1%) Spitz nevi. These findings suggest that the pattern of TRPM1 mRNA expression may be helpful in the differentiation of Spitz nevi and nodular melanomas. Of the 16 patients who experienced metastasis, 15 (94%) had primary tumors that displayed reduced MLSN mRNA expression by all or a part of the dermal tumor.

Superficial Black Network: An Additional Dermoscopic Clue for the Diagnosis of Pigmented Spindle and/or Epithelioid Cell Nevus

Dermoscopy is a valuable method for improving the diagnostic accuracy of pigmented skin lesions. Specific dermoscopic criteria have been described for differentiating pigmented spindle and/or epithelioid cell nevi (SECN; Spitz nevi and Reed nevi) from cutaneous melanomas. In the present study, we report an additional dermoscopic feature of SECN, namely a distinctive type of pigment network, described as superficial black network, which was observed in 10.5% of SECN. Histopathologically, this network corresponds to focal areas of pigmented parakeratosis, producing a black reticulated appearance on the horizontal plane.

The intermediate filament peripherin is expressed in cutaneous melanocytic lesions.

Peripherin is an intermediate filament involved in growth and development of the peripheral nervous system and is localized to neurons, some other cells derived from neural tube and neural crest, and some neuroendocrine cells (e.g. beta cells of islets of Langerhans). Peripherin also has been demonstrated in neuroblastomas and cutaneous neuroendocrine (Merkel cell) carcinomas. The expression of peripherin by other cells derived from the neural crest is unknown. We evaluated by immunohistochemistry 74 cutaneous melanocytic lesions including primary invasive malignant melanoma (IMM), melanoma in situ (MIS), atypical nevus (nevus with architectural disorder and cytologic atypia of melanocytes) (AN), spindle and epithelioid cell nevus (Spitz nevus) (SN), blue nevus (BN), and common intradermal benign melanocytic nevus (BMN) for expression of peripherin. Peripherin was detected in a cytoplasmic distribution within tumor cells in 14/14 IMM and 8/10 MIS. For IMM, peripherin localized to both the intraepidermal and invasive dermal components. Peripherin was detected in 10/10 AN and 9/9 SN, being localized to the intraepidermal component and, focally, to the superficial dermal component of the lesions. The dendritic nevus cells in 15/15 BN also expressed peripherin. For most of the BMN, expression of peripherin was absent or limited to rare, scattered cells in the superficial portion of the lesions. Melanocytes in adjacent normal skin were not labeled in any of the lesions studied. These results indicate that expression of peripherin is common in both benign and malignant melanocytic lesions, but not in normal resting adult melanocytes. Among benign lesions, expression of peripherin in the dermal component is rare except in the dendritic cells of BN. These findings provide evidence that the expression of peripherin, a marker of neuronal differentiation, is maintained by IMM, MIS, and BN, but is lost in the normal maturational sequence of the dermal component of other melanocytic lesions.

Giant recurrence of a multiple agminated Spitz nevus

An 11-year-old boy had multiple agminated pigmented lesions distributed over the left scapula since the age of 2 years. Shave excision of four grouped lesions showed Spitz nevi (benign juvenile melanoma, spindle or epithelioid cell nevi) that were not totally excised basally. Three years later, a tumorous, keloidlike nodule developed on that site. To the best of our knowledge, giant recurrence within an agminated Spitz nevus has not previously been reported.

“Malignant Spitz Nevus” in a 2‐Year‐Old Japanese Child

Smith et al. (1989) have reported a variant of Spitz's nevus with histological atypical features. Despite local lymph node metastases, further metastases were not observed. They proposed the name "malignant Spitz nevus" for this variant. A 2-year-old Japanese girl had a large nodule (27 x 17 mm) surrounded by an indurated erythema over the Achilles tendon. Histologically, it proved to be a melanocytic lesion resembling spindle cell and epithelioid cell nevus (Spitz's nevus) with unusual features; the tumor extended deep into the subcutis, and the mitotic figures deep into the tumor, together with prominent lymphatic vessel invasion by melanocytes. Thus the tumor was aptly termed "malignant Spitz nevus". Flow cytometric analysis of the DNA content revealed a diploid pattern. The child is well 5 years after a wide resection of the tumor. The diploid pattern of the DNA content as well as the good prognosis could support the idea that "malignant Spitz nevus" fits within the spectrum of Spitz's nevus.

Expression of proliferating cell nuclear antigen in Spitz nevus

Background: Epithelioid and spindle cell nevus (ESN; Spitz nevus) is a histologically well-described entity. We hypothesized that the features of ESN may reflect activation by a proliferative stimulus. Objective: Nevocytes and keratinocytes in ESN and control specimens were examined for expression of the proliferation marker, proliferating cell nuclear antigen (PCNA). Methods: Standard immunohistochemical methods were used to examine the expression of PCNA in a series of ESN, other nevi, and malignant melanoma. Results: PCNA was detected in nevocytes in a significant percentage of ESN but not in other nevi. PCNA expression was increased in basilar keratinocytes in ESN when compared with staining of basilar keratinocytes in normal epidermis. In other melanocytic nevi and nonin-flamed melanoma, PCNA expression in keratinocytes was similar to that in normal control tissue. Conclusion: Increased PCNA labeling in nevocytes and keratinocytes in ESN suggests that a growth stimulus, present within some of these lesions, affects both keratinocytes and nevocytes.

Nevoid melanoma: A clinicopathological study of seven cases of malignant melanoma mimicking spindle and epithelioid cell nevus and verrucous dermal nevus

We report seven cases of a distinctive type of malignant melanoma characterized by a deceptively benign histological appearance with an architecture resembling that of benign melanocytic nevi on scanning magnification. Two predominant architectural patterns were observed: a dome-shaped pattern (two specimens) and a verrucoid pattern (five specimens). The specimens with a dome-shaped pattern of growth were characterized by a smooth epidermal surface and a proliferation of epithelioid melanoma cells with an inconspicuous intraepidermal component resembling spindle and epithelioid cell nevi (Spitz nevi). Gradual diminution in the size of dermal nests toward the bases of the lesions simulating the maturation phenomenon of benign nevi was observed; however, the dermal organization in cords and strands of melanoma cells and the persistence of cellular atypia extending to the bases of the tumors allowed their recognition as malignant melanomas. On the other hand, the specimens with a verrucoid growth pattern consisted of broad, exophytic tumors with a verrucous epidermal surface resembling that of papillomatous dermal nevi but distinguished from them by the presence of a continuous proliferation of melanocytes along the dermal-epidermal junction and by confluent sheets of melanoma cells in the dermis without evidence of true maturation. Clinical follow-up showed local recurrence in three patients after intervals ranging from 5 months to 5 years and regional metastasis in one patient after 2 years. The lesions described here may constitute a serious pitfall for diagnosis because of their innocent silhouette on scanning magnification and their superficial resemblance to spindle and/or epithelioid cell nevi and benign verrucous melanocytic nevi. Proper attention to cytological detail and subtle architectural features will aid in recognizing this unusual variant of malignant melanoma.

Hyalinizing Spindle and Epithelioid Cell Nevus

Five cases are described of a distinctive histologic variant of benign spindle and epithelioid cell nevus characterized by extensive and prominent stromal hyalinization. The lesions consisted of a proliferation of spindle or epithelioid nevocytes scattered singly or in small clusters in the dermis and surrounded by abundant paucicellular hyalinized or collagenous stroma. Three patients were men and two were women. Their age range was 23 to 45 years (mean, 32). Two of the lesions were located in the head and neck region, two in the lower extremities, and one in the trunk. Immunohistochemical strains showed positive staining of the spindle or epithelioid cells with S-100 protein and vimentin; stains for keratin, EMA, CEA, actin, and desmin were all negative. Van Gieson and trichrome histochemical reaction demonstrated the collagenous nature of the hyalinized intercellular matrix; Congo red, crystal violet, and alcian blue stains were all negative. The etiology and pathogenesis of the intercellular hyalin deposits are unknown, but they probably represent a regressive phenomenon in longstanding or involuting lesions. Hyalinizing Spitz nevus must be included in the differential diagnosis of cutaneous lesions exhibiting a prominent hyalinized stroma and must be differentiated from other dermal neoplasms, particularly cutaneous metastases from occult internal malignancies and malignant melanoma.

Melanoma Mimicking Dermal and Spitz's Nevus (“Nevoid” Melanoma)

We describe two examples of malignant melanoma that present with clinical and histopathologic characteristics resembling the benign acquired dermal nevus and the spindle and epithelioid cell nevus (Spitz's nevus), respectively. Both lesions were present on the trunk of adult patients. The clinical impression in both cases was dermal nevus. Histopathologically, these lesions were fairly well circumscribed and symmetrical; they exhibited an expansile dermal proliferation of atypical nevomelanocytes in nests and fascicles with only minimal intraepidermal involvement. These lesions which we will designate as "nevoid" melanoma can be misinterpreted as benign nevi because of the absence of prominent intraepidermal pagetoid spread and the pattern of apparent dermal maturation at the base of the tumor associated with a gradual diminution of cell size. These features mimic the maturation phenomena in banal dermal nevi and spindle and epithelioid cell nevi. The differential diagnosis includes other types of melanoma, and various benign entities characterized by a predominantly dermal proliferative process, such as deep penetrating nevus and cellular neurothekeoma. The recognition of nevoid melanoma is critical so that patients with these lesions receive appropriate therapy for malignant melanoma.

Pigmented spindle cell nevus: A clinicopathologic analysis of ninety-five cases

Pigmented spindle cell nevus (PSCN) is often interpreted as a Spitz nevus or misdiagnosed as malignant melanoma. The purpose of this study was to analyze the clinical and histologic features and to determine the biologic behavior of 95 cases of PSCN. We reviewed clinical data, follow-up information, and microscopic features of all 95 cases of PSCN. PSCNs are dark brown to black, 3 to 6 mm in diameter, and occur most commonly on the extremities (75%) and back (16%) with a predilection for the legs. These lesions are more common in women in the third decade of life. Microscopically, PSCNs are characterized by uniform, spindle-shaped, pigmented melanocytes. Although some histologic features overlap with those in spindle and epithelioid cell nevus, PSCN is a separate entity. In addition, PSCN must be differentiated from malignant melanoma. Fifty-seven patients (60%) observed for an average of 6 years did not develop local recurrence or metastasis. PSCN is a distinctive, acquired, benign melanocytic lesion, that should not be confused with spindle and epithelioid cell nevus or malignant melanoma. Complete excision is recommended for treatment.

HMB-45 Staining in Benign and Malignant Melanocytic Lesions

The antibody HMB-45 used as an immunohistochemical reagent has often been labeled as a marker for melanoma, even though some benign lesions have been noted to show positive staining reactions with this reagent. Biopsy specimens from 225 benign and malignant melanocytic lesions were examined after immunoperoxidase staining for S-100 protein and HMB-45. The lesions studied included common acquired nevi, spindle cell and epithelioid cell nevi (Spitz nevi), cellular blue nevi, deep penetrating nevi, congenital nevi, nevi from hormonally reactive areas (genital), malignant melanoma, and desmoplastic malignant melanoma. A positive reaction for HMB-45 was seen in the dermal component in a high percentage of each of these types of lesions except for the common acquired nevi and the desmoplastic malignant melanomas that were uniformly negative for HMB-45 in the dermal component. HMB-45 correlates with melanosome production and thus a melanocytic origin of HMB-45-positive cells. HMB-45 may correlate best with factors that stimulate melanocytic proliferation and production of melanosomes.

Spindle and Epithelioid Cell Nevus (Spitz Nevus)

A clinical follow-up study of 49 cases of spindle and epithelioid cell nevus is presented to address the question about the potential for local recurrence. Only 19 (39%) of the 49 lesions were initially excised en toto, and the remainder (30 cases) had positive margins; six of the latter spindle and epithelioid cell nevi were reexcised, and no evidence of a residual nevus was found in five of the six cases. There were no recurrences in the 49 patients during an average follow-up period of 5.0 years (range, 1 to 10 years). The rarity of recurrent spindle and epithelioid cell nevus would justify a conservative approach to management, with clinical follow-up alone recommended after a subtotal excision, when the pathologic diagnosis is unequivocal.

Spitz nevus of the palate: Report of a case

A 4-year-old Japanese girl with a nonpigmented nodule on the anterior portion of the palate since birth is described. The overall microscopic appearance of the lesion was very similar to that of Spitz nevus of the skin. Diagnosis of Spitz nevus (mixed epithelioid cell and spindle cell nevus) was made on the basis of the clinical and histologic criteria for differentiating this lesion from malignant melanomas and common compound nevi. Positive immunostaining of epithelioid and spindle cells for S-100 protein and neuron-specific enolase was also indicative of their nevocellular nature. Review of the cases of Spitz nevus from the literature revealed that the present case most probably represents the first reported instance of this type of nevus in the oral cavity.

Ultrastructural study of nuclear inclusions in spindle and epithelioid cell nevus cells

The nuclei of spindle and epithelioid cell nevus (SECN) cells often contain inclusions. To determine the origin and pathogenesis of the nuclear inclusions, 12 cases of SECN were electron microscopically examined. True inclusions, pseudoinclusions, and electron-lucent areas were frequently found in the nuclei of SECN cells in all cases. The true inclusions were composed of various structures including vesicles and electron-dense homogenous substance. The pseudoinclusions were a cytoplasmic structure engulfed by nucleus; they were surrounded by a nuclear membrane and rich in cytoplasmic vesicles and electron-dense materials. Occasionally, a partial dissolution of the covering membrane of the pseudoinclusions was seen, leaving their contents in the nuclear matrix. It was concluded that a sequential process from the pseudoinclusions to the true inclusions in nuclei was morphologically present in SECN cells.

Frequency of Dysplastic Nevi Among Nevomelanocytic Lesions Submitted for Histopathologic Examination

All cutaneous nevomelanocytic specimens accessioned for histopathologic examination at Massachusetts General Hospital, Boston, in 1950, 1960, 1970, and 1987 were reviewed. The specimens were categorized as malignant melanoma, acquired or congenital benign nevi, blue nevi, spindle and epithelioid cell nevi, and dysplastic nevi. Other processes such as lentigines were excluded. There was a threefold increase in percentage of patients having nevomelanocytic lesions removed (1.5% in 1950 to 4.6% in 1987) compared with total surgical cases over the 37-year period. A progressive increase in numbers and percentages of dysplastic nevi (among nevomelanocytic surgical cases) was noted over a 37-year interval--2 cases (1% of nevomelanocytic cases) in 1950, 4 cases (2%) in 1960, 23 cases (5%) in 1970, and 189 cases (12%) in 1987. These findings confirm the existence of dysplastic nevi by histopathologic criteria as early as 1950 and illustrate the frequencies of various nevomelanocytic surgical specimens among all surgical specimens at four points in time over a 37-year period at a major referral center for pigmented lesions.

Cellular Neurothekeoma A Distinctive Variant of Neurothekeoma Mimicking Nevomelanocytic Tumors

We describe the clinical, histopathologic, and immunohistochemical characteristics of five examples of a distinctive subtype of neurothekeoma we term "cellular neurothekeoma" (CNT). These lesions are nondescript papules or nodules primarily involving the head and neck areas of young adults. Histopathologically, CNT are fairly well-defined proliferations involving the reticular dermis; they consist of fascicles of polygonal and spindle cells with eosinophilic or pale-staining cytoplasm and neuroid characteristics. Low-grade cytologic atypia and mitotic activity are common. All immunohistochemical markers--including S-100 protein, myelin basic protein, epithelial membrane antigen, and histiocytic antigens--have failed to show positivity in our laboratory. Separation from myxomatous variants of neurothekeoma is based on greater cellularity, less myxomatous change, and less pronounced plexiform compartmentalization by fibrous septae, which resemble perineurium. The differential diagnosis usually includes spindle and epithelioid cell (Spitz) nevus, malignant melanoma (particularly desmoplastic-neurotropic melanoma), cellular blue nevus, and fibrohistiocytic proliferations. The recognition of CNT and its differentiation from melanoma are important so that overly aggressive therapy is avoided.

A Case of an Unusual Mole

REPORT OF A CASE A 25-year-old woman complained about a conspicuous mole on the upper left aspect of her chest that had been present for at least 8 to 10 years. The mole was asymptomatic, dome-shaped, symmetrical, firm, and dark brown, and measured 4 × 4 mm (Fig 1). She believed that it was unsightly and requested that it be removed. It was excised and sent for histopathologic examination (Figs 2 through 4). What is your diagnosis? DIAGNOSIS: Combined Spitz nevus. DISCUSSION Spitz nevus, commonly known as benign juvenile melanoma or as spindle and epithelioid cell nevus, was originally thought to be a malignant neoplasm of childhood. 1 Since it was first described over 40 years ago, it has become evident that this melanocytic neoplasm has no malignant potential, is not confined to children, and may be pink, red, tan, or dark brown. 2,3