Expression and ultrastructural localization of HMB-45 antigen

HMB-45 is a monoclonal antibody specific for melanoma cells and premature developing melanocytes. We examined the expression and specific subcellular binding sites of HMB-45 in various types of melanocytes including epidermal melanocytes from fetuses and infants with or without tyrosinase-negative oculocutaneous albinism (type IA), melanin-producing and non-producing melanoma cell lines (G361 and MeWo), and in vivo melanoma cells (melanotic and amelanotic malignant melanoma). Subcellular HMB-45 binding was examined by using post-embedding immunogold electron microscopy with rapid freezing and freeze substitution fixation methods without the use of chemical fixatives to preserve the intracytoplasmic delicate antigen property of HMB-45. HMB-45 antigen was detected not only in in vivo melanoma cells and normal fetal melanocytes, but also in melanocytes in the other conditions. Post-embedding immunogold electron microscopy revealed that HMB-45 antigen was exclusively localized to stages I and II melanosomes in the cytoplasm of neoplastic melanocytes, but was detected mainly on stages II and III melanosomes in the melanocytes from fetuses and infants. In tyrosinase-negative oculocutaneous albinism, only stages I and II melanosomes were detected in the cytoplasm, but both stages of melanosomes were HMB-45 positive. We conclude that HMB-45 appears mainly on the immature melanosomes during melanogenesis in both neoplastic and non-neoplastic melanocytes regardless of their tyrosinase activity, but the intracytoplasmic localization of HMB-45 antigen is different by each condition of melanocytes.     

Effects of outcome expectancies and disinhibition on ad lib alcohol consumption

CD95 ligand (CD95L) potently induces apoptosis by activating CD95 on target cells. It has recently been reported that melanoma cells in vivo express a significant amount of CD95L, thereby being immediately able to kill CD95-bearing immunocompetent cells specific for cancer antigens, which infiltrate the lesions. In this study, we employed immunohistochemistry using an antibody directed against CD95L to investigate at which stage the melanoma CD95L expression is turned on. Skin biopsies of 49 lesions from 46 patients were assessed. These included benign and dysplastic naevi, melanoma in situ, stage I melanomas (Clark's level 2 or 3), advance-phase melanomas (Clark's level 4 or 5) and lymph node metastases. CD95L was expressed in all of the advance-phase melanomas as well as lymph node metastases of cutaneous origin, whereas neither melanoma in situ, benign naevi nor dysplastic naevi reacted positively with the antibody. To investigate a link between positivity and tumour size, the data were analysed on the basis of Breslow thickness, and indicated that expression was observed only when tumours were thicker than 0.75 mm. We next compared expression of CD95L and HMB-45. CD95L was positive only in melanomas in a more advanced phase than stage I, whereas HMB-45 was not only expressed in melanoma cells but also in benign pigmented naevi. This indicated the advantage of CD95L staining to diagnose melanoma. The present study indicates the significant correlation between tumorigenicity and expression of CD95L, and thereby raises the possibility that CD95L may be a useful diagnostic marker for malignant melanomas.     

Melanotic neuroectodermal tumour of infancy: an immunohistochemical and ultrastructural study

Two cases of melanotic neuro-ectodermal tumour of infancy (MNTI)--a rare neoplasm arising in the first year of life--are reported, with the results of immunohistochemical and ultrastructural examination. The tumours consisted of a biphasic cell population in a fibrous stroma. The small, darkly staining cells comprising the first population stained positively for synaptophysin, showing them to be neuroblasts, and the large epithelioid cells comprising the second cell population stained positively with the antibodies HMB-45 and NKI-Beteb, showing them to be melanocytes. Ultrastructural examination of the second case confirmed the biphasic nature of the tumour cells, with secretory granules and neurofilaments in the neuroblastic population, and melanosomes in the epithelioid population. These results add to the evidence supporting the neural crest origin of MNTI and confirm its formation from two distinct cell lines. Both cases have responded to local excision, with no recurrence more than a year after initial treatment.     

Giant plexiform schwannoma: a report of two cases with soft tissue and visceral involvement

We report two cases of massive, solitary, plexiform schwannoma. One was a 9-cm subcutaneous lesion on the hip of a 72-year-old man who had become aware of the slow-growing tumor 50 years earlier; the other is the first reported plexiform schwannoma to arise in a visceral organ: it arose in the ascending colon of a 54-year-old man and exhibited a dumbbell configuration with submucosal and subserosal components. Neither patient had neurofibromatosis or schwannomatosis. Both tumors were well-circumscribed and multinodular, and both showed a plexiform architecture. Microscopically, the nodules were composed primarily of Antoni A tissue, replete with nuclear palisading and Verocay bodies. Examination by immunohistochemistry and electron microscopy demonstrated the features of well-differentiated Schwann cells; nodules were surrounded by attenuated, residual perineurium. Both patients followed a benign clinical course, without recurrence or metastasis. Neither the large tumor size nor the unusual locations affected the biologic behavior of these neoplasms. A massive plexiform schwannoma must be distinguished from a malignant peripheral nerve sheath tumor and from a plexiform neurofibroma, a tumor prone to malignant transformation.     

Choroidal melanoma in an African-American albino

PURPOSE: To report the rare occurrence of choroidal melanoma in an African-American albino. METHODS: A 68-year-old African-American man with oculocutaneous albinism developed an amelanotic choroidal mass in his left eye. A transvitreal fine-needle aspiration biopsy was performed to confirm the diagnosis, and the patient was treated with iodine 125 plaque radiotherapy. RESULTS: The cytology of the needle biopsy showed spindle cells with nuclear atypia and prominent nucleoli. The cells showed positive immunoreactivity for HMB-45, supporting the diagnosis of choroidal melanoma. CONCLUSION: To our knowledge, this is the first reported case of a choroidal melanoma occurring in an African-American albino.     

Primary basal cell carcinoma of the limbal conjunctiva

BACKGROUND: The authors describe a 66-year-old man with primary basal cell carcinoma of the conjunctiva. He presented with a fleshy nodular conjunctival lesion of 4 months' duration, located at the nasal limbus of the left eye. No associated cutaneous lesions were present. RESULTS: The lesion was completely excised, and results of histopathologic examination showed a primary basal cell carcinoma of the conjunctiva. CONCLUSION: This report provides clinicopathologic evidence that primary basal cell carcinoma can rarely occur in the conjunctiva. The authors summarize two well-documented previously reported cases of this unusual lesion.     

Congenital superficial angiomyxoma

Superficial angiomyxomas are rare, benign, dermal and subcutaneous tumours. We describe a 12-year-old girl who presented with a nodular swelling in the midline of her scalp that had been present since birth. Histological examination revealed an ill-defined myxoid lesion within the dermis, comprising spindle cells, blood vessels and occasional multi-nucleate giant cells. Immunohistochemical staining was negative for S-100, cytokeratin and smooth muscle actin, but focally positive for CD34. Our patient is unusual in that the angiomyxoma was present at birth, which has not previously been described. The importance of screening patients with cutaneous myxomas for cardiac lesions is discussed.     

Retinal thickness variation in the diabetic patient measured by the retinal thickness analyser

BACKGROUND: Acral melanomas are uncommon. Due to the thick overlying stratum corneum, accurate estimation of margins is difficult for minimally pigmented or amelanotic melanomas on the palm or sole. OBJECTIVE: To describe the use of Mohs micrographic surgery using frozen sections and HMB-45 immunostaining in the treatment of a multiply recurrent acral melanoma that had failed both standard surgery and Mohs surgery. METHODS: The melanoma was excised by Mohs technique, and the margins were checked by frozen section and HMB-45 immunostaining. RESULTS: The melanoma was completely excised in 11 stages, resulting in a defect that covered much of the plantar surfaces of the ball of the left foot, great, second, third, fourth, and fifth toes. No recurrence has been noted in 22 months of follow-up. CONCLUSIONS: HMB-45 immunostaining is a very valuable adjunct to examination of surgical margins for melanoma, particularly when combined with such histologic features as clustering of cells, melanocyte position within the epidermis, and cytologic atypia.     

Ancient schwannoma of the submandibular gland: a case report

Schwannomas (neurilemmomas) are neurogenic tumors that arise from the Schwann cells of the neural sheath. They are most often benign and solitary. Extracranial schwannomas are rare, and can be mistaken for metastatic disease or other non-neurogenic tumors. Ancient schwannoma is a rare variant of schwannoma with a course typical of a slow-growing benign tumor. Histologically, it can be confused with a malignant mesenchymal tumor. An unusual case of an ancient schwannoma of the submandibular gland is reported. The clinical, histological and surgical aspects of this tumor are discussed, and the literature regarding this rare entity is reviewed.     

Taurolithocholate can inhibit the biliary discharge of lysosomes in the rat

This report concerns a 66-year-old man with a melanocytoma arising at the foramen magnum. Magnetic resonance imaging disclosed a well-circumscribed tumor extending from the medulla oblongata to C1 with gadolinium enhancement. A heavily pigmented tumor located under the leptomeninges was removed surgically. Although the patient died 8 months later of renal cell carcinoma, no recurrence or metastasis of the melanocytoma was detected by radiographic examination. Microscopically, the resected tumor was composed of polygonal to spindle-shaped cells containing large amounts of melanin. The bland nuclei of the tumor cells were of uniform size. No mitotic figures were seen. The tumor cells were positively immunostained for S-100 protein and by antibody HMB-45. They were not stained using the Ki-67 (MIB-1) antibody, indicating low proliferative activity. The ultrastructural examination revealed numerous mature melanosomes and basal laminae surrounding nests of cells. The tumor was diagnosed as a melanocytoma on the bases of its microscopic features and the lack of Ki-67 immunoreactivity. The ultrastructural and immunohistochemical features of melanocytomas are distinct from those of meningiomas. It is likely that melanocytomas and melanotic schwannomas represent opposite extremes of the continuous spectrum of neuroectodermal tumors derived from the neural crest.     

Tyrosinase, melan-A, and KBA62 as markers for the immunohistochemical identification of metastatic amelanotic melanomas on paraffin sections

The authors retrospectively tested the potential value of paraffin-reactive monoclonal antibodies (A103 against melan-A, T311 against tyrosinase) and antibody KBA62 as immunohistochemical markers for amelanotic metastatic melanomas. The study cases included 72 amelanotic metastases of known cutaneous melanomas, 59 poorly differentiated carcinomas, 73 sarcomas of varying histogenesis, 4 Leydig cell tumors, 10 high-grade lymphomas, and 6 plasmoblastic/anaplastic myelomas. The results were compared with immunostainings for S-100 protein and HMB-45. HMB-45, antimelan-A, and antityrosinase showed almost identical staining results, with a sensitivity of 0.85 for HMB-45 and of 0.86 for both antimelan-A and for antityrosinase. HMB-45 and antityrosinase both had a specificity of 1.00; the specificity of antimelan-A was 0.95 as a result of a positive reaction in three of three adrenocortical carcinomas and four of four Leydig cell tumors. KBA62 stainings resulted in a sensitivity of 0.86 for melanomas. A positive immunoreactivity of KBA62 alone had a specificity of only 0.83, but in conjunction with anti-S-100 protein (sensitivity, 1.00; specificity, 0.87) and anticytokeratin 8/18/19 (CK), a KBA62+/S-100+/CK- immunophenotype identified all except one of the melanoma cases that were negative for the three melanocyte-specific markers with a specificity of 0.99. In conclusion, we found comparable immunohistochemical sensitivities of HMB-45, antityrosinase, and antimelan-A for a highly specific identification of approximately 85% of amelanotic metastatic melanomas on paraffin sections. Melanomas that were negative for all of these specific markers might be sensitively and specifically detected with anti-S-100 protein and KBA62.     

Activation of epidermal melanocytes is independent of epithelial proliferation and vascularization. Immunohistologic study using HMB-45 antibody with review of the literature

Antibodies against HMB-45 antigen are widely used in the immunohistochemical investigation of melanocytic tumours as a marker of activation. While malignant transformation is one explanation for HMB-45 expression, we searched for other factors by investigating 252 biopsies of non-melanocytic skin lesions with 21 different diagnoses for the presence of HMB-45, using both single and double staining techniques. Epidermal melanocytes in lesions with an increased epithelial proliferation-either neoplastic or reactive-and lesions with a prominent vasculature showed an enhanced expression of HMB-45. The results indicate that the presence of HMB-45 is not only influenced by primary melanocytic changes but also may be dependent on epithelial proliferation and vascular factors. These mechanisms should be considered when interpreting HMB-45 staining of melanocytic lesions.     

Atypical angiomyolipoma of the kidney: a distinct morphologic variant that is easily confused with a variety of malignant neoplasms

BACKGROUND: The purpose of this study was to fully characterize and emphasize the salient features of an unusual variant of angiomyolipoma that the authors believe has been underrecognized. METHODS: Five cases of atypical angiomyolipoma (AAML) of the kidney, two of which were reported previously, were retrieved from the consultation files of one of the authors. In one patient a small extrarenal tumor was examined in addition to the primary renal tumor. The histopathologic features of all six tumors, the immunohistochemical findings of five tumors (including the extrarenal tumor), and the ultrastructure of three tumors were analyzed. Clinical follow-up was obtained for all patients. RESULTS: Two tumors occurred in children and presented as large masses (> or = 15 cm), and 2 tumors were small (< 5 cm) and affected middle-aged adults; the remaining tumor, of intermediate size (6 cm), occurred in an adolescent. One child with tuberous sclerosis also had a small (2 cm) extrarenal lesion. All tumors were circumscribed and had a red-brown cut surface. The largest tumors showed areas of hemorrhage and necrosis. The tumors were highly cellular and composed of various types of multinucleated and mononuclear cells. The most distinguishing of these, and virtually pathognomonic of this entity, were huge cells with abnormal strap-like and ameboid configurations having copious eosinophilic hyaline cytoplasm and myriad nuclei disposed peripherally in a ring-like fashion. Ganglion-like cells, polygonal cells, and spindle cells also were observed. For the most part, all cell types shared the same nuclear features, and except for one tumor, mitoses were negligible. The cells displayed a perivascular arrangement, and grew as loosely organized sheets oriented around abnormally dilated vascular channels or in a hemangiopericytic pattern; glomeruloid vessels were variably present. Notably, adipose tissue was inconspicuous. The tumors stained positive for HMB-45 protein, smooth muscle specific actin, and muscle specific actin antibodies, with a tendency for immunoreactivity to segregate along with individual cell phenotypes. Immunoperoxidase stains also disclosed a prominent and consistent intratumoral histiocytic component and a T-cell lymphoid infiltrate. Ultrastructurally, the tumor cells were replete with organelles showing highly electron-dense granules. All patients underwent radical nephrectomy; three patients with significant follow-up remain free of disease. CONCLUSIONS: AAML exhibits unusual but distinctive "pseudomalignant" histomorphologic features that facilitate its recognition, and a singular immunohistochemical profile that allows diagnostic confirmation. It occurs both sporadically and in association with tuberous sclerosis, affects both the adult and pediatric populations, and has shown an indolent behavior. AAML attests to the biologic and morphologic diversity that characterizes tuberous sclerosis hamartomata in general, and to the plasticity of the yet unclarified precursor of angiomyolipoma in particular.     

High-Na+ low-K+ UW cold storage solution reduces reperfusion injuries of the rat liver graft

Pure sarcomas of the uterine cervix are rare; most of those reported have been leiomyosarcomas or rhabdomyosarcomas. Minimal data exists on malignant nerve sheath tumors in this site; only one typical example and one melanocytic example have been reported. We report three additional examples here in three patients 25, 65, and 73 years of age. The two older patients had vaginal bleeding and underwent hysterectomy as initial treatment. The youngest patient initially underwent only polypectomy. The tumors were 1.3, 4.4, and 5.0 cm in greatest dimension. The tumors were red-grey to white: two were polypoid and the third was ulcerated. The dominant microscopic appearance was that of cellular fascicles of spindle cells with hyperchromatic nuclei and eosinophilic cytoplasm. However, hypocellular areas were striking in each case; the hypocellular areas were fibromatous in two tumors and two had areas with a myxoid stroma (prominent in one). One tumor focally had cellular aggregates with a swirling pattern within a hypocellular background. Epithelioid foci in which tumor cells were rounded with conspicuous eosinophilic cytoplasm were focally prominent in one case. Mitoses were readily identified in each case. All three tumors were positive for S-100 protein and vimentin and negative for cytokeratin. HMB-45, and desmin. One case is recent and one patient had multiple metastases in the abdomen 2 years after hysterectomy. The patient treated initially by polypectomy underwent repeat local excision, followed by cone biopsy with positive margins, and then hysterectomy. She is clinically free of disease 15 months after diagnosis. Although the diagnosis of malignant schwannoma was suggested by the histologic features of the tumors, other diagnoses were entertained and immunohistochemistry was crucial in confirming the diagnosis. These tumors should be distinguished from other malignant spindle cell tumors of the cervix, such as leiomyosarcoma, endocervical "stromal sarcoma," and spindle cell melanoma, so their features, behavior, and optimal therapy can be further delineated.     

Dimethylnitrosamine and nitrosopyrrolidine in fumes produced during the frying of bacon

An unusual case is reported of an occult, spontaneously rupturing, hemorrhagic, metastatic melanoma of the liver treated by hepatic lobectomy, resulting in short-term survival. A long, symptom-free interval (13 years) after excision of the primary cutaneous lesion (stage I) preceded the appearance of the hepatic metastasis. This case illustrates the need for a careful and thorough history as well as the benefit of prompt hepatic resection for bleeding from ruptured hepatic malignancies.     

Both the tool and the carpenter are important

A 67-year-old woman with a history of a skin melanoma that was excised 7 years previously had a 6-month history of decreased vision in her right eye. A choroidal melanoma was diagnosed clinically, and the eye was enucleated. The results of a histopathological examination revealed a primary uveal melanoma. Slides of the skin melanoma were obtained, and the initial diagnosis was confirmed. In an attempt to illustrate a biological difference between the 2 melanomas, immunohistochemical studies were performed on sections of the 2 specimens using S-100 protein, HMB-45, and S-100-beta. Primary cutaneous and choroidal melanomas appearing in a patient with no predisposition are rare; this is believed to be only the fifth such case reported in the literature.     

Metastatic pulmonary, gastric, and renal calcification demonstrated on bone scintigraphy in a patient with malignant melanoma and renal failure

PURPOSE: This case report describes the clinical, scintigraphic, and pathologic findings in a patient with an unexpected finding of a cutaneous malignant melanoma. METHOD: Multiple imaging studies were done, as was a pathologic examination of a suspicious pigmented lesion on the patient's back. RESULT: A Tc-99m MDP bone scan showed diffuse uptake in the skeleton, lungs, kidneys, and stomach. CONCLUSION: Metastatic calcification, as shown by isotope scintigraphy, is an unusual manifestation of metastatic cancer from a primary cutaneous melanoma.     

Comparison of several mouse and rat monoclonal antibodies against human fibrinogen

A rare case of desmoplastic melanoma arising from the maxillary gingiva of a 66-year-old woman is reported. This tumour metastasised to the submandibular lymph node 5 years after extirpation, and local recurrence was observed 2 years later. The gingival tumour showed the histopathological characteristics of desmoplastic melanoma and the metastasised tumour cells were immunohistochemically positive for S-100 protein, neuron specific enolase, HMB-45 highly specific for conventional melanoma, and Fontana-Masson staining. The gingival tumour, originally regarded as benign clinically, was actually a desmoplastic melanoma.     

A rapidly enlarging neck mass

We presented an unusual case of cutaneous and bilateral ovarian metastases of malignant melanoma. There was no previously identifiable cutaneous or mucous lesion or teratoid element. Past history revealed that the patient had undergone removal of a blackish, elevated, irregular shaped tumor from the right arm eleven years previously. This lesion was considered to be the primary melanoma; therefore, it was thought to be very unusual as metastasis occurred in both the skin and ovaries after an eleven year disease-free interval.     

Clear cell "sugar" tumor of the lung: association with lymphangioleiomyomatosis and multifocal micronodular pneumocyte hyperplasia in a patient with tuberous sclerosis

We report the unique association of a clear cell "sugar" tumor of the lung (CCTL) in a 32-year-old woman with tuberous sclerosis (TSC), lymphangioleiomyomatosis (LAM), and multifocal micronodular pneumocyte hyperplasia (MMPH). Chest radiographs demonstrated a peripheral solitary 1.0-cm lingular nodule, diffuse emphysematous changes, and bilateral pneumothorax. Microscopic examination of the coin lesion showed an unencapsulated tumor composed of round to oval to focally spindled cells with distinct cellular borders, abundant clear to eosinophilic granular cytoplasm, prominent thin-walled blood channels, and focal hyaline stroma. Rare multinucleated cells were identified, and neither necrosis nor mitotic figures were seen. Tumor cells contained abundant diastase-sensitive intracytoplasmic glycogen, as demonstrated with periodic acid-Schiff stains. Tumor cell immunoreactivity for HMB-45 and nonreactivity for cytokeratin supported the diagnosis. The lung tissue also contained MMPH and smooth muscle proliferations diagnostic of LAM. The histogenesis of CCTL remains controversial, and similarities between this lesion and both LAM and angiomyolipoma (AML) raise the possibility that these lesions are related not only to each other, but that CCTL should be added to the spectrum of pulmonary manifestations of TSC.