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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.
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PMID:Spitz's nevi with halo reaction: a histopathologic study of 17 cases. 944 88

A seventeen-year-old Korean girl had a reddish-brown papular lesion on the nose. Histopathologically, it proved to be a "hyalinizing Spitz nevus" with the characteristic features of a discohesive growth pattern of nevus cells and hyalinized stroma. Immunohistochemical stains showed positive reactivity of nevus cells with S-100 protein and Vimentin and negative stainings with HMB45, CD68, CEA and low molecular weight cytokeratin. Hyalinizing Spitz nevus may represent a variant in the spectrum of Spitz nevus.
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PMID:Hyalinizing Spitz nevus. 1082 93

Histiocytic tumors can be confused with melanocytic nevi and malignant melanoma and vice versa. To explore the use of immunohistochemistry for this diagnostic problem, we examined the expression of S-100 protein, gp100 (the antigen recognized by HMB-45), tyrosinase (T311), Melan-A (A103), Factor XIIIa (FXIIIa), and CD68 in 10 juvenile xanthogranulomas (JXGs), five epithelioid histiocytomas (EHs), and 15 melanocytic nevi composed of large epithelioid cells. All epithelioid melanocytic nevi were immunoreactive for Melan-A, tyrosinase, and S-100 protein in most melanocytes. Four nevi were completely negative with HMB-45. Nine nevi had only a minor HMB-45-positive component in the superficial dermis. Two nevi were diffusely HMB-45-positive. Melanocytes in all nevi were completely negative for FXIIIa. Thirteen nevi were completely negative for CD68. Two nevi contained rare cells with weak staining for CD68. All 15 histiocytic proliferations were completely negative for Melan-A, tyrosinase, and gp100. They lacked expression of S-100 protein or had at most 10% immunopositive cells. In JXGs, most cells were strongly reactive for CD68, although only a few were positive for FXIIIa. In EHs, 40% to 60% of cells were immunoreactive for FXIIIa, and only 20% to 30% were positive for CD68. Our results demonstrate that Melan-A and tyrosinase are sensitive and specific markers to distinguish epithelioid melanocytic nevi from epithelioid histiocytic tumors.
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PMID:Immunohistochemical distinction of epithelioid histiocytic proliferations from epithelioid melanocytic nevi. 1087 Oct 66

A 54-year-old man presented with a recurrent swelling on the right occipital region of the scalp. Two months earlier, the patient had undergone an initial local excision of the lesion which had enlarged progressively over the previous 2 years on a hairless patch which had been present since birth. On examination, a 5 x 4-cm, pinkish, firm, ulcerated swelling was seen on the right occipital region with a scar running over it. The lesion was not fixed to the underlying bone and there was no regional lymphadenopathy. X-Ray of the skull was normal and no evidence of metastatic disease was identified. Wide local excision of the tumor was performed and it was sent for histopathologic examination. Specimens and slides of the earlier surgery performed elsewhere were also studied. The specimen of the initial surgery consisted of skin-covered tissue with an exophytic firm growth measuring 6 x 5 x 4 cm. The skin surface was rough with areas of ulceration. No necrosis was noted grossly. Microscopically, three distinct lesions were seen. One was a well-circumscribed tumor located in the superficial dermis with lobules of basaloid cell aggregates with peripheral palisading and with no epidermal connection. The lobules were surrounded by cellular fibrous tissue (Fig. 1). Unlike basal cell carcinoma, however, no cleft between the cellular aggregates and stroma was noted. Foci of pigmentation were seen within cellular lobules and these features were consistent with a diagnosis of tricho-blastoma. The second tumor was seen adjacent to the first, and consisted of duct-like structures and cystic spaces with papillary projections. These were lined by double-layered epithelium with stromal infiltration by plasma cells, which are features of syringocystadenoma papilliferum (Fig. 2). The third lesion was a spindle cell sarcoma which formed the major part of the lesion, diffusely infiltrating the dermis and subcutaneous tissue, elevating and ulcerating the overlying skin. The tumor consisted of interlacing fascicles of spindle cells with oval to elongated nuclei having finely dispersed chromatin and inconspicuous nucleoli. The tumor cells were seen encircling the sweat glands, without destroying them (Fig. 3). Nuclear pleomorphism was minimal, with a mitotic rate of 9-10 per high-power field. A small area of epidermal hyperplasia with acanthosis and papillomatosis overlying malformed highly placed sebaceous glands was the only evidence of a pre-existing nevus sebaceus. The status of the surgical margins was not clearly discernible. The wide excision specimen of the recurrent swelling consisted of a skin-covered nodule with ulceration, measuring 3 x 4 x 3 cm, with a gray-white whorled cut surface. No necrosis was noted grossly. Multiple sections showed only spindle cell sarcoma infiltrating the skin and subcutaneous tissue, morphologically similar to the earlier tumor, with ulceration of the overlying skin. The surgical margins were free from tumor. Immunohistochemical stains on the spindle cell sarcoma showed positive staining for smooth muscle actin (SMA) (Fig. 4), vimentin, epithelial membrane antigen (EMA), and S100. The tumor cells were negative for cytokeratin (CK), HMB45, desmin, glial fibrillary acidic protein (GFAP), CD34, and CD68. Correlating the histomorphology and immunohistochemical findings, a diagnosis of cutaneous leiomyosarcoma with tricho-blastoma and syringocystadenoma papilliferum arising on nevus sebaceus was made. The patient received postoperative radiotherapy and is disease free 8 months after diagnosis.
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PMID:Cutaneous leiomyosarcoma, trichoblastoma, and syringocystadenoma papilliferum arising from nevus sebaceus. 1734 92

Fibrous papule of the face is a common benign lesion located most often on the nose. It presents usually as a single small, firm, skin-coloured papule and is often misdiagnosed as melanocytic naevus, wart or small nodular basal cell carcinoma. Histopathologically, the lesions are characterized by involvement of the upper dermis by a fibrovascular proliferation and scattered triangular or stellate, often multinucleated cells. Uncommon histopathologic variants of fibrous papule of the face include hypercellular, clear-cell, pleomorphic, pigmented, inflammatory and granular-cell types. We present here a patient with the syndrome of familial cancer and fibrous papule of the face with granular cells. The granules stained strongly with PAS stain, as well as with CD68 and NKI/C3 immunostains, whereas S-100 protein resulted negative. In our patient the mutations in the 2 most often affected DNA mismatch repair genes of Muir-Torre syndrome were not found, therefore the origin of the familial cancer syndrome remains unknown. Probably the occurrence of the granular-cell fibrous papule of the face was coincidental.
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PMID:Fibrous papule of the face with granular cells. 1838 5

PU.1 is a transcription factor restricted to the hematopoietic system. It is expressed in myeloid lineage and B lymphocytes but is absent in mature T cells and nonhematopoietic cells. Among myeloid lineage-derived cells, PU.1 is overexpressed in monocytes, histiocytes, and dendritic cells. We evaluated PU.1 expression in 78 cases of primary skin neoplasms, including 9 reticulohistiocytomas, 9 Langerhans cell histiocytoses, 7 juvenile xanthogranulomas, 9 fibrous papules, 8 dermatofibromas, 12 dermatofibrosarcoma protuberans, 9 Spitz nevi, and 15 malignant melanomas. Strong nuclear staining for PU.1 was seen in all cases of histiocyte and dendritic cell origin, including 9/9 reticulohistiocytomas, 9/9 Langerhans cell histiocytoses, and 7/7 juvenile xanthogranulomas. No staining for PU.1 was seen in any studied cases of fibrous papules, dermatofibrosarcoma protuberans, dermatofibromas, Spitz nevi, or malignant melanomas. This study indicates that PU.1 is a valuable immunohistochemical marker for identifying cutaneous histiocyte- and dendritic cell-derived lesions. PU.1 staining is easily interpreted due to the sharp nuclear staining as compared with the irregular and often variable cytoplasmic staining seen with CD68.
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PMID:The utility of PU.1 as an immunohistochemical marker for histiocytic and dendritic lesions of the skin. 1954 15

Cutaneous clear cell proliferations and degenerative change have been seen in a variety of entities including nevi, dermatofibromas, fibrous papules, atypical fibroxanthomas, basal cell carcinomas, and squamous cell carcinomas, to name a few. However, there have been no reports of clear cells within neurofibromas. We received a biopsy and excision from a 61-year-old man with a papule on his right lateral clavicle. The initial biopsy showed a proliferation of clear cells that stained positive with S-100 and focally with CD68. A clear cell granular cell tumor was favored. Subsequent excision showed the same population of clear cells as seen on the initial biopsy. Interestingly, a neurofibroma was also present immediately beneath the clear cells with areas of transition. A p75 stain highlighted both populations of cells. This is the first case of neurofibroma with clear cells reported in the literature. We postulate that the clear cells are due to degenerative change.
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PMID:Neurofibroma with clear cell change. 1954 19

Epidermal tissue repair represents a complex series of temporal and dynamic events resulting in wound closure. Matricellular proteins, not normally expressed in quiescent adult tissues, play a pivotal role in wound repair and associated extracellular matrix remodeling by modulating the adhesion, migration, intracellular signaling, and gene expression of inflammatory cells, pericytes, fibroblasts and keratinocytes. Several matricellular proteins show temporal expression during dermal wound repair, but the expression pattern of the recently identified matricellular protein, periostin, has not yet been characterized. The primary aim of this study was to assess whether periostin protein is present in healthy human skin or in pathological remodeling (Nevus). The second aim was to determine if periostin is expressed during dermal wound repair. Using immunohistochemistry, periostin reactivity was detected in the keratinocytes, basal lamina, and dermal fibroblasts in healthy human skin. In pathological nevus samples, periostin was present in the extracellular matrix. In excisional wounds in mice, periostin protein was first detected in the granulation tissue at day 3, with levels peaking at day 7. Periostin protein co-localized with alpha-smooth muscle actin-positive cells and keratinocytes, but not CD68 positive inflammatory cells. We conclude that periostin is normally expressed at the cellular level in human and murine skin, but additionally becomes extracellular during tissue remodeling. Periostin may represent a new therapeutic target for modulating the wound repair process.
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PMID:Periostin localizes to cells in normal skin, but is associated with the extracellular matrix during wound repair. 1954 15

Endothelin-1 (ET-1) is a vasoactive peptide that also plays a role in the tanning response of the skin. Animal and cell culture studies have also implicated ET-1 in melanoma progression, but no association studies have been performed to link ET-1 expression and melanoma in humans. Here, we present the first in-vivo study of ET-1 expression in pigmented lesions in humans: an ET-1 immunohistochemical screen of melanocytic nevi, melanoma in situ lesions, invasive melanomas, metastatic melanomas, and blue nevi was performed. Twenty-six percent of melanocytic nevi and 44% of melanoma in situ lesions demonstrate ET-1 expression in the perilesional microenvironment, whereas expression in nevus or melanoma cells was rare to absent. In striking contrast, 100% of moderately to highly pigmented invasive melanomas contained numerous ET-1-positive cells in the tumor microenvironment, with 79% containing ET-1-positive melanoma cells, confirmed by co-staining with melanoma tumor marker HMB45. Hypopigmented invasive melanomas had reduced ET-1 expression, suggesting a correlation between ET-1 expression and pigmented melanomas. ET-1-positive perilesional cells were CD68-positive, indicating macrophage origin. Sixty-two percent of highly pigmented metastatic melanomas demonstrated ET-1 expression in melanoma cells, in contrast to 28.2% of hypopigmented specimens. Eighty-nine percent of benign nevi, known as blue nevi, which have a dermal localization, were associated with numerous ET-1-positive macrophages in the perilesional microenvironment, but no ET-1 expression was detected in the melanocytes. We conclude that ET-1 expression in the microenvironment increases with advancing stages of melanocyte transformation, implicating a critical role for ET-1 in melanoma progression, and the importance of the tumor microenvironment in the melanoma phenotype.
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PMID:Endothelin-1 in the tumor microenvironment correlates with melanoma invasion. 2682 37

A 4-month-old infant presented with asymptomatic soft nodules on his right forearm, which had developed since birth. On the suspicion of nevus lipomatosus superficialis (NLS), biopsy was performed. Histopathologic findings showed monomorphic polygonal cells with abundant granular cytoplasm. Immunohistochemical stains for CD68 and vimentin were strongly positive, but were negative for S-100 protein. Based on the pathologic findings, the patient was diagnosed as non-neural granular cell tumor (NN-GCT). GCT can be divided into conventional and non-neural GCT by immunoreactivity for S-100 protein. NN-GCT is typically manifested as a well-circumscribed, papulo-nodular dermal mass, and is known to occur in a younger group than does in conventional GCT, but is rare among children. To our knowledge, there have been no case reports of NN-GCT which appeared at birth and presented as grouped nodules. Therefore, we report this interesting case of congenital NN-GCT clinically mimicking NLS.
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PMID:Congenital Non-Neural Granular Cell Tumor Mimicking Nevus Lipomatosus Superficialis. 2920 Jul 68


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