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PubMed1997

Silhouette symmetry: an unsupportable histologic criterion for distinguishing Spitz nevi and compound nevi from malignant melanoma.

BACKGROUND: In 1989, Ackerman proposed that pattern analysis can be a more accurate method of evaluating neoplasms than assessment of nuclear morphology. He stated that malignant melanomas tend to be asymmetrical, and benign melanocytic neoplasms tend to be symmetrical. METHODS: We examined a series of typical Spitz nevi, compound nevi, and malignant melanomas with the loupe and with higher magnifications. We also considered pattern analysis from the standpoint of solid geometry. RESULTS: The ratio of symmetrical to asymmetrical lesions (visualized in histologic sections) in malignant melanomas approximated that of Spitz nevi and compound nevi. The configuration seen in sections does not necessarily reflect the three-dimensional configuration of a lesion. Lesions with three-dimensional reflective symmetry cannot be shown to have this property in sections unless cuts are made perpendicular to the plane of symmetry, which is an impossibility. CONCLUSIONS: The presence or absence of symmetry in sections of neoplasms must be considered coincidental or focal. Using symmetry as a criterion to distinguish malignant melanomas from Spitz nevi and compound nevi is without validity on both theoretical and empirical grounds.

Diagnosis, Differential↗

PubMed2001

S100A6 preferentially labels type C nevus cells and nevic corpuscles: additional support for Schwannian differentiation of intradermal nevi.

BACKGROUND: Melanocytic nevi typically show a morphologic sequence of maturation from epithelioid "type A" cells to fusiform, Schwann cell-like "type C" cells with dermal descent. Nevi may also produce Wagner-Meissner-like structures (nevic corpuscles). Previous studies have shown that this maturation of intradermal nevi recapitulates intermediate stages in Schwann cell development. In intradermal nevi, we have evaluated the pattern of S100A6 protein, a form of S100 found in Schwann cells. METHODS: Formalin-fixed, paraffin-embedded archival tissues were evaluated by immunohistochemistry using antibodies specific for S100A6 and S100B in 38 intradermal nevi (IDN). Ten neurofibromas (NF), 3 Schwannomas (SCH), 2 palisaded and encapsulated neuromas (PEN), and 2 granular cell tumors (GCT) were included as positive controls since these lesions have large numbers of Schwann cells. RESULTS: Melanocytic nevi demonstrated preferential anti-S100A6 staining of "type C" cells (36/38; 28 strong, 8 weak) and nevic corpuscles (25/38; 19 strong, 6 weak) compared to "type A" cells (17/38; 17 weak) and "type B" cells (17/38; 4 strong, 13 weak). All NF, SCH, and PEN stained strongly with anti-S100A6. Both GCT were negative with anti-S100A6 but positive with anti-S100B. CONCLUSIONS: The pattern of S100A6 expression in intradermal nevi further supports the hypothesis that maturation in these lesions recapitulates features of Schwann cell differentiation. The lack of S100A6 expression by both GCT suggests that these lesions have lost this feature of Schwann cells, which may play a role in their peculiar phenotypic appearance.

Cell Cycle Proteins↗

PubMed1998

Ancient melanocytic nevus.

Ancient melanocytic nevus is an example of a simulator of malignant melanoma, designated ancient because it shares numerous features with ancient schwannoma. Knowledge of the histopathologic characteristics of this benign melanocytic neoplasm should enable pathologists to avoid overdiagnosis of it as melanoma arising in the intradermal portion of a nevus. Ancient nevi are found most commonly on the face of older persons. The neoplasm is usually a dome-shaped, skin-colored or reddish brown papule, usually with features of a Miescher's nevus. Histopathologically, ancient nevi are exoendophytic, mostly intradermal proliferations of two populations of melanocytes: one with large pleomorphic nuclei and the other with small monomorphous ones. The large melanocytes may resemble those of the epithelioid type of Spitz's nevus. A few mitotic figures may be present in a particular section. The epidermis usually is uninvolved, but sometimes there may be a junctional component. Other important findings are degenerative changes that include thrombi, zones of hemorrhage, pseudoangiomatous changes, thick rims of sclerosis around dilated venules, fibrosis, and mucin. Ancient nevi frequently are misdiagnosed as melanoma arising in an intradermal nevus.

Aged↗

PubMed1997

Agminated intradermal Spitz nevi arising on an unusual speckled lentiginous nevus with localized lentiginosis: a continuum?

We report an 18-year-old boy with a congenital pigmented lesion measuring 2 x 6 cm on his right thigh. About a third of the lesion was composed of numerous lentiginous macules superimposed on histologically normal and clinically nontan skin; in the remainder of the lesion, several macules and papules with histologic features of junctional and compound nevi were superimposed on clinically normal skin, which had a lentiginous pattern histologically. Some years later, eruptive intradermal Spitz nevi developed at one corner of the lesion. The combined clinical and histological features of the lesion fulfill descriptions for both segmental lentiginosis and an unusual variant of speckled lentiginous nevus. Our case points out the limitations of using strict diagnostic criteria to define speckled lentiginous nevus and offers an opportunity to consider the natural history of the lesion as a continuum from lentigines to melanocytic nevi. Moreover, the presence of eruptive intradermal Spitz nevi arising within the area of speckled lentiginous nevus lacking a distinct tan background, suggests the possibility that the entire area of the lesion per se constitutes an environment where development of nevi is enhanced.

Adolescent↗

PubMed2002

Persistent (recurrent) Spitz nevi: a histopathologic, immunohistochemical, and molecular pathologic study of 22 cases.

This report describes 22 Spitz nevi that seemed to have been clinically removed but persisted and clinically recurred at the biopsy site. These were evaluated in terms of histopathology, immunohistochemistry, and molecular pathology using comparative genomic hybridization (CGH) and fluorescent in situ hybridization. One of these 22 lesions was originally reported as an atypical melanocytic proliferation with some features of a Spitz nevus and was included in the study set at an early stage but was later recognized as melanoma after metastasis to regional lymph nodes 3 years after the local recurrence. We noted four histopathologic patterns in the recurrent lesions: 1) a predominantly intraepidermal pattern resembling "pseudomelanoma" as seen in recurrent "common" melanocytic nevi, 2) a compound, mostly nested pattern above or within a scar that was nearly identical to the originally biopsied Spitz nevus, 3) a nodular growth pattern that closely simulated invasive melanoma, and 4) a desmoplastic pattern resembling an intradermal desmoplastic Spitz nevus. Although the majority of recurrent lesions exhibited asymmetry and pagetoid spread, the dermal component usually had a low mitotic rate and retained architectural and cytologic maturation, which allowed distinction from invasive melanoma. Except for the metastasizing melanoma, the immunostaining pattern with S-100 and HMB-45 was identical to that previously reported for Spitz nevi. Ki67 revealed a very low proliferation rate in all cases, including the melanoma. CGH performed in 10 cases yielded results consistent with Spitz nevi in eight cases. The remaining two cases showed CGH profiles more typical of melanoma, and one of these was the above-referenced case of melanoma, proven by metastasis. Although ancillary molecular techniques such as CGH are of great help in distinguishing these from melanoma, until such techniques become widely available we advocate complete but conservative excision of any recurrent Spitz nevus.

Adolescent↗

PubMed1996

Congenital plantar melanocytic nevus with satellite lesions.

We report a case of a congenital melanocytic nevus accompanied by a mucous cyst and satellite pigmented macules on the undersurface of the left great toe in a 17-year-old Japanese man. Myxoid change was confirmed by the discharge of viscous liquid when conducting biopsy of the tumor. Besides such an unusual clinical feature of the tumor, accompanying satellite lesions led us initially to consider the possibility of malignant melanoma. However, a biopsy specimen obtained from the tumor revealed the typical features of intradermal type melanocytic nevus. In a specimen obtained from the satellite pigmented lesion, there was a small mass of nevus cells underneath the basement membrane zone, suggestive of having originated from the spread of nevus cells through lymphatic vessels.

Adolescent↗

PubMed1998

Which direction do nevus cells move? Abtropfung reexamined.

In 1893, Unna published his theory of Abtropfung in which he suggested that melanocytic nevus cells originate in the epidermis and drop off into the dermis. We studied 3,534 nevi from patients of all ages to reassess this almost sacred concept. If Unna was correct, one would expect that in childhood most nevi would be junctional, while in late adult life almost all nevi would be intradermal. In our series, no child under age 10 had a purely junctional nevus, 52% had compound nevi, and 48% had dermal nevi. In patients older than age 60, 12% had junctional nevi, 23% had compound nevi, and 65% had dermal nevi. Our data fail to support the concept of Abtropfung; they fit better with the contradictory theory of upward migration of nevus cells.

Adolescent↗

PubMed1985

Inherited corneal snowflake dystrophy with oculocutaneous pigmentation disturbances and other symptoms.

A new type of corneal dystrophy with various oculocutaneous symptoms and other signs is described. Snowflake dystrophy is characterized by hundreds of small, round, oval or cork-screw-like white opacities in the endothelium and Descemet's membrane. The length of the opacities is 5-20 mu and they form an even layer throughout the posterior membrane. 44% of the patients above the age of 70 years had also pseudoexfoliation of the lens capsule. Corneal endothelial pigmentation advance with the age but are not even in elderly patients necessarily present. A wide range of cutaneous disturbances of melanin metabolism was noted in 4/5 of the cases: intradermal nevi, lentigines, nevus spilus, melasma, vitiligo, early alopecia and early graying of the hair. Photosensitivity reactions like solar urticaria were noted in 5 cases. The skin was often wrinkled, dry and inelastic. Conjunctival wrinkling and Bitot's spots, ovarial cysts, frequently recurrent tonsillitis and several cholecystectomies suggest a generalized involvement of mucous membranes in this syndrome. Degenerative joint disease was constated in 2/5 of cases. The genetic analysis of 59 persons revealed an autosomal dominant mode of inheritance. The prevalence of the gene was high in the province of Satakunta in western Finland.

Adult↗

PubMed1984

A survey of cutaneous neural lesions for the presence of myelin basic protein. An immunohistochemical study.

The presence of myelin basic protein (MBP) within a skin neoplasm would support its derivation from Schwann's cells, since this substance is routinely present within Schwann's cells in the peripheral nervous system. Using a monoclonal antibody prepared against MBP and an unlabeled antibody peroxidase-antiperoxidase assay, we surveyed a variety of skin lesions suspected of being derived from Schwann's cells to determine whether MBP was present. Myelin basic protein was detected within the cytoplasm of cells composing benign solitary schwannoma (neurilemmoma) and neurofibroma, confirming the association of these lesions with proliferation of Schwann's cells. Myelin basic protein was not found in a variety of intradermal and compound nevus cell nevi nor in malignant melanoma. This negative finding supports electron microscopic evidence suggesting that nevus cells have no relationship to Schwann's cells even though some nevus cell arrangements suggest Schwann's cell derivation under the light microscope.

Animals↗

PubMed1992

Epithelioid cell histiocytoma. A clinicopathologic and immunohistochemical study of eight cases.

BACKGROUND: Epithelioid cell histiocytomas histologically resemble the intradermal form of Spitz nevus. OBJECTIVE: We have studied eight patients with epithelioid cell histiocytoma. METHODS: In addition to the routine stains, histologic sections were prepared by immunohistochemical techniques for S-100 protein, HMB-45, vimentin, alpha 1-antitrypsin, and common leukocyte antigen. RESULTS: Epithelioid cell histiocytoma is characterized by proliferation of angulated epithelioid cells with abundant eosinophilic cytoplasm. Immunostaining for S-100 protein and HMB-45 were negative. The majority of cells had positive reactions to staining for vimentin and alpha 1-antitrypsin. Approximately 20% to 25% of cells also gave positive reactions to common leukocyte antigen. CONCLUSION: Immunostainings are useful in the differential diagnosis of epithelioid cell histiocytoma from the intradermal form of Spitz nevus.

Adult↗

PubMed1997

Spitz's nevi with halo reaction: a histopathologic study of 17 cases.

Halo reactions to melanocytic nevi are a well-recognized phenomenon. In contrast, halo reactions to Spitz's nevi have been reported only infrequently. Halo reactions may cause misdiagnosis of an otherwise benign nevus as melanoma because inflammatory cells sometimes obscure the architectural features of the underlying nevus, and may induce cytologic atypia. For Spitz's nevus where the distinction between malignancy and benignancy is already challenging, halo reactions compound the problem. We describe 17 examples of Spitz's nevus with halo reaction, and compare their immunohistochemical features with those of "ordinary" halo nevi. Only 2 of 17 lesions demonstrated clinically apparent halos. Clinical follow-up was available for 12 of 17 cases. None of the 12 has persisted at the biopsy site or metastasized after an average 3.6-year follow-up period. Junctional, compound, intradermal, and combined types of Spitz's nevi were represented. All were characterized by symmetrical lymphocytic infiltrates which permeated the full thickness of the nevus, including junctional nests. Combined Spitz's nevi constituted more than one-half of examples in this series (9/17 cases). The combined Spitz's nevus included a combination of Spitz's nevus with either an ordinary (common, banal) nevus or a superficial congenital type nevus. In these combined Spitz's nevi, the lymphocytic response was often directed exclusively to the Spitz's nevic component. Important distinguishing features from malignant melanoma arising in a pre-existing nevus included symmetry and lateral circumscription of the spitzoid component, no large expansile-appearing aggregates of melanocytes, a decrease in size of nests with increasing dermal depth, a lack of mitotic figures among melanocytes at the base, and a symmetrical and diffusely permeative lymphocytic response. Although the combined Spitz's nevus with halo reaction sometimes appeared asymmetrical at scanning magnification, each component of the combination was symmetrical, when examined independently. Probably because of reactive atypia, nuclear maturation with progressive descent into the dermis was sometimes absent. There were no obvious differences in immunohistochemical staining patterns among 4 Spitz's nevi with halo reaction, 5 regressing melanomas, and 5 benign halo nevi when stained with antibodies to S100, HMB-45, OPD4, CD8, TIA-1, CD1a, CD68, and Ki-67.

Adolescent↗

PubMed2000

Congenital spitz nevus.

BACKGROUND: Congenital Spitz nevus has been reported previously in the literature, but the histopathologic features have not been examined in detail. OBJECTIVE: To histologically examine and report on congenital Spitz nevus. METHOD: We examined 10 clinically submitted congenital melanocytic nevi that were histopathologically identified as congenital Spitz nevi and compared them to the characteristics seen in acquired Spitz nevus and superficial congenital melanocytic nevus. RESULTS: Of the 10 congenital Spitz nevi, 9 were compound and 1 was dermal. Two showed features of combined Spitz nevus (Spitz and blue). Six cases showed all 16 listed characteristics of acquired Spitz nevus, with two cases having 15 and two cases having 14 characteristics. Of the superficial congenital melanocytic nevus characteristics, all except three cases had all 12 attributes. The one dermal lesion had all the characteristics of the acquired Spitz nevus and all but one of the characteristics of the superficial congenital melanocytic nevus in regards to intradermal findings. CONCLUSIONS: Congenital Spitz nevi are true congenital lesions, with histopathologic features of both acquired Spitz nevus and superficial congenital melanocytic nevus.

Adolescent↗

PubMed2004

Comparison of characteristics of acquired bilateral nevus of Ota-like macules and nevus of Ota according to therapeutic outcome.

Both acquired bilateral nevus of Ota-like macules (ABNOM) and nevus of Ota are characterized by the presence of dermal melanocytes. There are no differences in the method of treatment, however, postinflammatory hyperpigmentation (PIH) develops more often in ABNOM than in nevus of Ota following treatment. We investigated the differences in the development of PIH after treatment between ABNOM and nevus of Ota, and the histopathologic differences in the PIH. A total of 82 patients with ABNOM (n=47) and nevus of Ota (n=35) were treated with Q-switched alexandrite laser and followed up 2 weeks and 3 months later. Biopsies were performed on lesional skin before treatment. The distribution and the amount of melanin pigments were visualized with Fontana-Masson stain, and the distribution and the depth of melanocytes were measured by GP-100 (NK1-beteb) stain. Clinically, there was more erythema and PIH in ABNOM than in nevus of Ota. Histopathologically, intradermal melanocytes were clustered in groups and dispersed perivascularly in ABNOM, while melanocytes were scattered evenly throughout the dermis in nevus of Ota. Both groups show that when there is a statistically significant number of melanocytes in the perivascular area, erythema and PIH occur after laser therapy. In conclusion, indirect vessel injury in addition to perivascular clustering melanocytes might be considered the cause of increased PIH after treatment in ABNOM.

Adolescent↗

PubMed1983

Fibrous papule: an immunohistochemical study with an antibody to S-100 protein.

We studied twenty biopsies taken from fibrous papules which were located in the central part of the face. The lesions, which were characteristic histologically, did not contain S-100 protein within the stellate cells in the papillary dermis, nor was this substance found in mesenchymal cells with some features of nevus cells. In control studies, S-100 protein was found using an unlabeled antibody peroxidase-antiperoxidase technic within nevus cells composing junctional intradermal, and compound nevi, Spitz nevi, and halo nevi. It therefore seems unlikely that fibrous papule represents a form of degenerated nevus as some investigators have proposed.

Biopsy↗

PubMed1994

Mucinous eccrine nevus.

We report a solitary lesion with histologic characteristics of an organoid nevus occurring on the lower extremity of a forty-seven-year-old woman. This lesion is thought to represent a variant of eccrine nevus composed of an intradermal proliferation of hyperplastic eccrine sweat glands with associated mucinous change.

Eccrine Glands↗

PubMed1987

Immunohistochemical localization of melanoma-associated antigen p94 kd200 with the use of a modified avidin-biotin-complex lectin method.

The immunohistochemical localization of melanoma-associated antigen p94 kd200 was investigated in frozen sections of 3 congenital nevi, 4 benign intradermal nevi, 1 regressing nevus, 1 blue nevus, 1 dysplastic nevus, 1 lentigo maligna, 1 superficial spreading melanoma and 2 metastatic melanomas. The original avidin-biotin complex lectin method (Hsu SM, Raine L, Fanger H: Am. J. Clin. Pathol., 75: 734-738, 1981) was modified to detect the antigen. The sections were exposed to the monoclonal antibody to p94 kd200 (Hybritech Inc.), the linking biotin-labelled anti-mouse IgG, the avidin-biotin peroxidase complex and the 3-amino-9-ethylcarbazole solution in an incubator at 37 degrees C and 100% humidity. We found that the percentage of cells expressing p94 kd200 varied between 0 and 100% in congenital nevi, between 80 and 100% in benign intradermal nevi, between 0 and 20% in the regressing, blue and dysplastic nevi, and in the lentigo maligna, 80 to 100% in the superficial spreading melanoma, and between 0 and 40% in the metastatic melanomas. Positive cells were found to be hypomelanotic (did not have heavy melanin content). The intensity of labelling or the degree of antigen expression on benign and malignant hypomelanotic cells was also found to vary. These findings 1) reinforce the concept of quantitative rather than qualitative antigenic differences in benign and malignant cells 2) suggest that kd200 is lost with increasing pigment production 3) offer a potentially significant tool to investigate the antigenic changes during cell differentiation.

Antigens, Neoplasm↗

PubMed1986

Increased nevus estrogen and progesterone ligand binding related to oral contraceptives or pregnancy.

Melanocytic nevi excised from women who were pregnant or had given birth less than 1 month previously or from women who were taking oral contraceptives were studied with the use of a fluorescent estrogen and progesterone ligand binding assay. All nevi from these patients had markedly increased numbers of estrogen- and progesterone-binding cells, similar to those observed in melanoma and melanoma precursor lesions. In contrast, nevus cells in acquired intradermal nevi from women who were not pregnant nor taking oral contraceptives had few or no detectable estrogen- or progesterone-binding cells. The induction of increased hormonal receptors by pregnancy or oral contraceptives may be related to an increased risk of melanoma and melanoma precursor lesions in specific subsets of patients, as well as to the pigmentary changes observed in female patients in general.

Adult↗

PubMed1986

Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes.

The authors have generated monoclonal antibodies to an extract of melanoma. When tested on a variety of fixed, embedded sections of malignant tumors, one antibody (HMB-45) reacted with 60 of 62 melanomas and none of 168 nonmelanomas (carcinomas, lymphomas, and sarcomas). The antibody reacts with junctional nevus cells but not intradermal nevi, and recognizes fetal and neonatal melanocytes but not normal adult melanocytes. This antibody thus demonstrates absolute specificity for melanocytic tumors and thus has great utility for the surgical pathologist in distinguishing among poorly differentiated tumors of uncertain origin. It also identifies differences among populations of melanocytes which may be useful in understanding the biology of and interrelationships between these cells.

Animals↗