myelin-basic-protein and Skin-Neoplasms

Neurothekeoma, a benign cutaneous lesion of probable nerve sheath origin, is divided histologically into two subtypes--myxoid and cellular. However, we believe that neurothekeoma encompasses a wider spectrum of lesions, with the myxoid and cellular subtypes falling at either end of the morphologic spectrum. Because the cellular variant of neurothekeoma sometimes resembles melanoma, it presents a difficult diagnostic problem. We report the histologic and immunohistochemical findings in 14 cases of neurothekeoma and review the findings in 35 additional cases from the literature. A detailed analysis of the histologic spectrum is also included. When examined by immunostains, only the myxoid variants of neurothekeoma stain positively for S-100 protein. We conclude that when the histological differential diagnosis is between cellular neurothekeoma and melanoma, an S-100-positive lesion should be regarded as melanoma.

Topics: Adult; Aged; Cell Nucleus; Child, Preschool; Collagen; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Male; Melanoma; Membrane Glycoproteins; Middle Aged; Mucin-1; Mucins; Myelin Basic Protein; Neoplasm Proteins; Neurothekeoma; S100 Proteins; Skin Neoplasms; Staining and Labeling; Transglutaminases

Topics: Alkaline Phosphatase; B-Lymphocytes; Carcinoembryonic Antigen; Cytoskeleton; Dermatitis, Atopic; Humans; Immunoenzyme Techniques; Immunoglobulins; Langerhans Cells; Lectins; Microscopy, Electron; Myelin Basic Protein; Neoplasms, Nerve Tissue; Nerve Tissue Proteins; Papillomaviridae; Peanut Agglutinin; Plant Lectins; Skin Diseases; Skin Neoplasms; T-Lymphocytes; Tumor Virus Infections

In previous studies, we have obtained a notable anti-tumor efficacy of the recombinant MUC1-MBP vaccine in the process of mouse B16-MUC1 melanoma treatment. However, the tumor cannot be eliminated completely. We found that the tumor inhibition rate decreased from 81.67% (five immunizations) to 43.67% (eight immunizations) after more than five immunizations, indicating persistent vaccine stimulation may activate immunosuppressive factors. In the present study, we revealed that programmed cell death 1 (PD1), an inhibitory molecule suppressing T cell function, expressed on splenic and tumor-infiltrating T cells were up-regulated by the vaccine. Therefore, to optimize the anti-tumor efficacy of the vaccine, we employed combination immunotherapy with MUC1-MBP vaccine and αPD1 (anti-PD1 antibody). Results showed that combination immunotherapy induced a more remarkable anti-tumor efficacy, the tumor clearance being increased to 80% from 20% which obtain by MUC1-MBP vaccine immunizations. To investigate the possible underlying mechanism, IFN-γ secretion and cytotoxic T lymphocyte (CTL) cytotoxicity were measured by enzyme-linked immunosorbent assay (ELISA) and xCELLigence real-time cell analyzer (RTCA) respectively. T cell subsets and immunosuppressive cells in the mouse spleen and tumor microenvironment were analyzed by FACS. Results showed that the proportion of splenic CD8

Topics: Animals; Cancer Vaccines; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Female; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Melanoma, Experimental; Mice; Mucin-1; Myelin Basic Protein; Myeloid-Derived Suppressor Cells; Programmed Cell Death 1 Receptor; Recombinant Fusion Proteins; Skin Neoplasms; Th1 Cells; Tumor Microenvironment; Vaccines, Synthetic

We report on eight cases of a distinct variant of cutaneous schwannoma characterized by prominent Verocay body formation (75-100% of the tumor bulk) that may cause considerable diagnostic difficulties. Like ordinary cutaneous schwannomas, these lesions preferred the head and neck region of young adults without sexual predilection and were clinically interpreted as cyst, basal cell carcinoma, or nevus. Histological examination revealed well-circumscribed nodules. Three of them consisted exclusively of nodular or ribbon-like Verocay bodies. A variable admixture of Antoni A or B type of differentiation (< 25%) was seen in five other cases. The following patterns were seen: fascicular spindle-shaped, onion-like epithelioid, myxoid-hypocellular, and degenerated ("ancient") with prominent fibrosis/hyalinosis and occasional bizarre giant cells. Immunohistochemically, the lesions were positive for S-100 protein (and vimentin) but negative for a broad panel of neurogenic and intermediate filament markers. The capsule showed focal labeling for EMA and--when it was markedly thickened--also for SMA. Labeling with E9, an anti-metallothionein marker indicative of cell activity, was negative, underscoring the slow growth potential of these lesions. No recurrence was seen in the six patients with follow-up information. The differential diagnosis includes other lesions with prominent palisading. (Amianthoid) myofibroblastoma and palisading leiomyoma are consistently positive for SMA and desmin, respectively. Palisading cutaneous fibrous histiocytoma and myofibroblastic dermatofibroma are variably positive for Factor XIIIa, SMA, and E9 and/or NK1C3 (CD57). Palisaded encapsulated neuromas are primarilly differentiated by the presence of nerve fibers with myelin sheaths.

Topics: Adolescent; Adult; Aged; CD57 Antigens; Desmin; Female; Glial Fibrillary Acidic Protein; Head and Neck Neoplasms; Humans; Immunohistochemistry; Male; Middle Aged; Myelin Basic Protein; Neurilemmoma; Phosphopyruvate Hydratase; S100 Proteins; Skin Neoplasms; Transglutaminases

We report a case of nevus spilus with neurotized nevus studied by immunohistochemical methods using S-100, leu-6, glial fibrillary acid protein (GFAP), and myelin basic protein (MBP). Histologic findings of the speckled lesion showed irregular rete ridge elongation, increased epidermal melanocytes and melanin in the epidermis, and scattered nevus cell nests in the upper dermis, but showed neurotized nevus in the deep dermis, which has many features of neurofibroma. Diffuse expression of S-100 protein and MBP, focal staining with GFAP, and lack of staining with leu-7 were observed, Leu-7, positive only in neurofibromas and not in neurotized nevus, appears to be the more pertinent method for distinguishing neurotized nevus from neurofibroma.

Topics: CD57 Antigens; Child; Female; Glial Fibrillary Acidic Protein; Humans; Myelin Basic Protein; Nevus, Pigmented; S100 Proteins; Skin Neoplasms; Toes

The primary hyperplastic nature of palisaded encapsulated neuromas (PENs) has been recently challenged by suggesting a traumatic origin. We studied eight cases of traumatic neuroma (TN) and 12 cases of PEN by routine light-microscopic, histochemical, and immunohistochemical methods to assess evidence of previous tissue injury. Sections from the formalin-fixed, paraffin-embedded tissue were stained with hematoxylin-eosin, trichrome, elastic, reticulin, Giemsa, colloidal iron (with and without hyaluronidase), and Bielschowsky silver stains. Antibodies were applied to collagen types I, III, and IV, MAC 387, factor XIIIa, alpha 1-antitrypsin (A1AT), epithelial membrane antigen (EMA), Leu-7, and myelin basic protein using ABC techniques. We found that (a) in TN the individual fascicles were usually surrounded by perineurial cells, whereas in PEN the perineurial cells were observed mainly in the capsular areas and only rarely within the fascicles as evidenced by EMA antibodies; (b) histochemically TN contained considerably larger amounts of collagen (types I and III), acidic mucin, and myelin products than did PEN; and (c) neither PEN nor TN contained increased inflammatory cells or cells positive for factor XIIIa, MAC 387, or A1AT. We conclude that (a) there are substantial structural and histochemical differences between TN and PEN, (b) the changes suggest that the classic form of PEN has a different histogenesis than TN, and (c) on histologic grounds, chronic minor trauma could not be excluded as an etiologic factor for PEN.

Topics: alpha 1-Antitrypsin; Antigens, Differentiation; Antigens, Neoplasm; Collagen; Humans; Immunohistochemistry; Membrane Glycoproteins; Mucin-1; Myelin Basic Protein; Neuroma; Skin; Skin Neoplasms; Transglutaminases

Neurofibromas are often clinically, as well as histologically, indistinguishable from completely neurotized melanocytic nevi. We tested the hypothesis that immunologic markers would differentiate the perineural fibroblasts and Schwann cells of neurofibromas from the neurotized cells of melanocytic origin. We examined eight partially neurotized acquired melanocytic nevi, three partially neurotized congenital melanocytic nevi, and five neurofibromas, with antibodies directed against S-100 protein, Leu-7(HNK-1), glial fibrillary acid protein (GFAP), and myelin-basic protein (MBP). A histologic diagnosis of neurofibroma was based on identification of a dermal proliferation of spindle-shaped cells with wavy nuclei, in a background of loose reticulated collagen. Neurotized nevi were diagnosed upon recognition of scattered nests of type A or B nevus cells, surrounded by basement membrane, present in the papillary dermis of lesions otherwise indistinguishable from neurofibromas. The congenital nevi were all large melanocytic nevi known to be present at birth. S-100 stained the majority of neoplastic cells in all neurofibromas, neurotized acquired nevi, and neurotized congenital nevi. Neurofibromas showed focal staining for Leu-7, GFAP, and MBP. In contrast, neurotized acquired and congenital nevi failed to express these markers. We believe that Leu-7, GFAP, and MBP may be helpful in differentiating neurofibromas from completely neurotized melanocytic nevi. The differences in the immunohistochemical profiles of neurofibromas and neurotized nevi support the concept that these neoplasms are histogenically distinct, despite their similar histologic appearance.

Topics: Antigens, Differentiation; Antigens, Surface; Biomarkers, Tumor; Cell Transformation, Neoplastic; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Killer Cells, Natural; Melanocytes; Myelin Basic Protein; Neurofibroma; Nevus, Pigmented; S100 Proteins; Skin Neoplasms; Staining and Labeling

Fourteen nevi with neuroid zones were examined and compared with nine nevi without neuroid structures. At light microscopic level, nevus cells from the neuroid nevi and the control nevi show the same staining pattern with polyclonal antibodies against S-100 protein. Around the cells of the neuroid zones is a more intensive immunoreactivity with monoclonal antibodies against laminin and collagen type IV than around the nevus cells in the upper dermis and the nevus cells in the control nevi. Also, the Gordon-Sweet stain for reticulin shows a dense network around the cells of the neuroid zones. No immunoreactivity in the neuroid zones was found with monoclonal antibodies against myelin-basic protein, myelin-associated protein, and glial fibrillary acidic protein. At the electron microscopic level, nevus cells from the neuroid zones show stacks of elongated cytoplasmic processes surrounded by basal lamina material. This pattern explains the presence of the abundant cytoplasm seen at light microscopy. Because no features of neural or neurolemmal differentiation could be found, the exactitude of the term neurotization can be questioned.

Topics: Antigens, Surface; Biomarkers, Tumor; Cell Transformation, Neoplastic; Collagen; Cytoplasm; Histocytochemistry; Humans; Laminin; Melanocytes; Microscopy, Electron; Myelin Basic Protein; Myelin Proteins; Myelin-Associated Glycoprotein; Nevus; S100 Proteins; Schwann Cells; Skin Neoplasms

Eleven cases of palisaded, encapsulated neuroma (PEN) were studied by routine light microscopic and immunohistochemical methods. PEN showed the following staining reactions: strong, diffuse for S-100 protein (11/11) and collagen Type IV (Col. IV) (11/11); moderately strong, focal for myelin basic protein (MBP) (9/11) and Leu-7 (9/11); weak, focal for MBP (2/11), Leu-7 (2/11), neuron specific enolase (NSE) (4/11), neural filaments (NF) (5/11), epithelial membrane antigen (EMA) (6/11), and negative for glial fibrillary acidic protein (GFAP). Bielschowsky silver stain was positive in 11/11, but only four cases contained numerous axons. Col. IV and EMA stains showed a complete capsule in 1/11, incomplete capsules in 5/11 and no discernible capsules in the remainder. We concluded that (1) the immunologic profile of PEN is not specific; (2) conventional silver stain remains a suitable method to demonstrate axon-like structures; (3) the ratio of axons to Schwann cells is variable and generally less than 1:1, as previously assumed; (4) MBP and Leu-7 coexpression in Schwann cells suggests myelinization of some of the nerve fibers; (5) the pattern of EMA reaction supports perineurial cell involvement in PEN; and (6) despite the current definition of PEN, they are usually not completely encapsulated as evidenced by Col. IV and EMA strains.

Topics: Antigens, Differentiation; Antigens, Neoplasm; CD57 Antigens; Collagen; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Intermediate Filaments; Membrane Glycoproteins; Mucin-1; Myelin Basic Protein; Neuroma; Phosphopyruvate Hydratase; S100 Proteins; Skin Neoplasms

One hundred and two cases of benign nerve sheath tumors (NSTs) were studied with a combined approach using routine light microscopy (LM), immunohistochemistry (IH) for myelin basic protein (MBP) and S-100 protein as well as transmission electron microscopy (TEM) with the aim of obtaining greater insight into the true nature of these neoplasms, and also to establish the importance of IH and TEM in their diagnosis. Myelin basic protein was not identified in any of these tumors, whereas S-100 protein was positive to a variable degree in both schwannomas and neurofibromas. TEM revealed that Schwann cells predominated in tumors which were strongly positive for S-100 protein and appeared as schwannomas by LM. However, neurofibromas showing a variable patchy positivity for S-100 were composed of an admixture of Schwann cells, fibroblast-like cells and intermediate cells considered to be modified Schwann cells. Perineurial cells in typical form were not seen. It is concluded that all NSTs are basically of Schwann cell origin and that the intermediate cells and fibroblast-like cells are variants of Schwann cells. The different morphological appearances and biological behaviour of schwannomas and neurofibromas may be related to some other factors like micro-environment or genetic predisposition. Further, both IH, especially for S-100 protein, and TEM play an important role in establishing their diagnosis.

Topics: Cranial Nerve Neoplasms; Humans; Immunohistochemistry; Microscopy; Microscopy, Electron; Myelin Basic Protein; Neoplasms, Nerve Tissue; Neurilemmoma; Neurofibroma; S100 Proteins; Schwann Cells; Skin Neoplasms; Spinal Cord Neoplasms

Topics: beta 2-Microglobulin; Glial Fibrillary Acidic Protein; Histocytochemistry; Humans; Immunochemistry; Microscopy, Electron; Myelin Basic Protein; Neoplasms, Muscle Tissue; S100 Proteins; Schwann Cells; Serotonin; Skin Neoplasms

Substance P (SP), S-100 protein, methionine-enkephalin, serotonin and myelin basic protein were studied in two solitary glomus tumours of the skin by peroxidase-antiperoxidase immunohistochemistry. Multiple SP-containing nerve fibres were distributed in the parenchyma of the tumour among proliferating glomus cells, and in the oedematous stroma of the tumour. Positive staining for myelin basic protein was detected in nerve fascicles in the capsule of the tumour, but not within the glomus tumour. S-100 protein immunoreactivity was found in nerve fascicles in the capsule of the tumour, and in addition, a few cells positive for S-100 protein were scattered throughout the stroma of the tumour. No positive staining for methionine-enkephalin and serotonin was found. The present finding may explain the clinical experience that the tumour is tender and can cause severe paroxysmal pain, because SP is known to be a primary sensory afferent neurotransmitter for mediating nociception. A possible role of SP for vasodilation in the glomus tumour is also discussed.

Topics: Enkephalin, Methionine; Glomus Tumor; Humans; Immunoenzyme Techniques; Myelin Basic Protein; Nerve Fibers; S100 Proteins; Serotonin; Skin Neoplasms; Substance P

Immunohistochemical localization of tissue specific or cell-specific antigenic markers in neoplastic cells has become an increasingly important tool in the pathologic diagnosis of tumors. The myelin-specific proteins of peripheral nervous system myelin, because they are normally synthesized in Schwann cells, are potentially useful markers for neoplasms arising from peripheral nerves. The authors carried out immunohistochemical studies on 18 cases of Schwann cell neoplasms, including schwannomas, neurofibromas, and granular cell tumors, to determine whether two myelin-specific proteins, myelin basic protein and P2 protein, were present in neoplastic Schwann cells. None of these tumors showed immunostaining for either myelin basic protein or P2 protein in neoplastic cells. In contrast, S-100 protein, which is a well established marker for normal and neoplastic Schwann cells, was localized by immunohistochemistry to neoplastic cells in all 18 neoplasms. Therefore, although myelin basic protein and P2 protein are known to be Schwann-cell-specific proteins, they do not appear to be expressed commonly in neoplastic Schwann cells.

Topics: Histocytochemistry; Humans; Immunologic Techniques; Myelin Basic Protein; Myelin P2 Protein; Neoplasms, Muscle Tissue; Neurilemmoma; Neurofibroma; S100 Proteins; Schwann Cells; Skin Neoplasms; Soft Tissue Neoplasms

A malignant spindle cell tumor with features of a malignant schwannoma presented as a skin mass in the neck of a 13-year-old child. The histologic diagnosis was supported by the demonstration of myelin basic protein within the atypical cells using a monoclonal antibody to myelin basic protein and an unlabelled antibody peroxidase-antiperoxidase technique.

Topics: Adolescent; Cytoplasm; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Myelin Basic Protein; Neck; Neurilemmoma; Skin Neoplasms

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.

Topics: Animals; Antibodies, Monoclonal; Histocytochemistry; Humans; Immunoenzyme Techniques; Melanoma; Mice; Mice, Inbred BALB C; Myelin Basic Protein; Neurilemmoma; Neurofibroma; Nevus, Pigmented; Skin Neoplasms; Swine

Myelin basic protein, a substance found in neural structures, has been demonstrated in cutaneous granular cell tumors using a monoclonal antibody generated against myelin basic protein and an immunoperoxidase method. The substance was not found in fibrohistiocytic skin lesions. The presence of myelin basic protein in granular cell lesions of the skin supports the concept that this lesion is related closely to nerve structures.

Topics: Animals; Antibodies, Monoclonal; Humans; Immunoenzyme Techniques; Mice; Mice, Inbred BALB C; Myelin Basic Protein; Neurilemmoma; Skin Neoplasms

The electrophoretic mobility test (EMT) is an in vitro assay for demonstrating cellular immunity. In the presence of tumor antigens lymphocytes of tumor patients liberate lymphokines, which reduce the charge of indicator particles resulting in a measurable reduction of their eletrophoretic mobility. Lymphocytes of 174 patients were tested by EMT. The antigens used were a basic myelin protein termed encephalitogenic factor (EF) and a 3M KCl extract from melanoma tissue. In 91% of the cancer patients there was a positive lymphocyte response. In contrast to this the controls and non-malignant diseases showed a positive result in only 8.7% of the cases. Using the 3M KCl extract from melanoma tissue as tissue as antigen 1 of the benign controls, 3 patients with nonmalignant diseases and none of the 49 patients with malignant diseases reacted positively, whereas in the melanoma group 86% showed a positive lymphocyte response. The results show the possibility of demonstrating tumor specific immune reaction in the EMT.

Topics: Antigens; Antigens, Neoplasm; Female; Humans; Immunity, Cellular; Immunoelectrophoresis; In Vitro Techniques; Lymphocytes; Lymphokines; Male; Melanoma; Myelin Basic Protein; Skin Neoplasms