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Biomedical subjects

M C Mihm

Publications and source records attributed to M C Mihm.

At least 253 records · Page 14Linked to original sources

Clinical and pathological correlation of malignant melanoma.

We have attempted to review virtually all forms of cutaneous and mucocutaneous melanomas. Superficial spreading, lentigo maligna and nodular melanomas have been more thoroughly investigated and documented in previous studies. Lentigo maligna melanoma appears to have a longer duration and better prognosis than SSM or NM. The overall prognosis probably correlates better with the anatomic level and thickness of invasion than with type (Clark et al. 1975, Breslow 1970, 1975). It appears that certain pitfalls exist in either method of assessing prognosis, and it is recommended that both methods be applied in evaluating a malignant melanocytic lesion when feasible. With regard to in situ melanoma or Level I melanoma, it is our experience that such lesions can achieve a 100% cure rate when completely excised. Hence, we prefer to call such lesions severely atypical melanocytic hyperplasia, and thus avoid labeling these patients with a malignant diagnosis. The most difficult histologic challenge in diagnosing a lesion of malignant melanoma is the Spitz nevus. The pathologist should never be biased by the age of the patient, for a serious mistake can arise. We have seen a case of nodular melanoma in a 13-year-old girl diagnosed as Spitz nevus only to be followed by a lymph node metastasis years later. Other examples of histologic differential diagnoses of malignant melanomas include, for example, halo nevus, soft tissue sarcoma, squamous cell carcinoma with spindle cell proliferation, Paget's disease of metastatic carcinoma, (for example, from the breast). Therefore, the approach to the diagnosis of malignant melanoma necessitates an evaluation of both clinical and pathological features. Histologic study must encompass both the pattern of growth and cellular cytologic detail for successful interpretation.

Conjunctiva↗

Morphologic and functional evidence for release of mast-cell products in bullous pemphigoid.

We studied nine patients with bullous pemphigoid, a generalized cutaneous eruption- for evidence of mast-cell involvement during development of lesions. As in other reports, six of nine patients demonstrated a serum antibody directed against the epidermal basement-membrane zone. Direct immunofluorescence studies of lesions revealed depostion of immunoglobulin and complement proteins at the basement-membrane zone in six of nine and nine of nine patients, respectively. Participation of mast cells was suggested by a sequence of pathologic alterations in which there was progressive mast-cell degranulation and late eosinophil infiltration. In addition, a factor chemotactic for human eosinophils with the size and charge characteristics of the eosinophil chemotactic factor of anaphylaxis was identified in blullous fluid. The data indicate that, in addition to activation of the complement system, involvement of mast cells is an early and continuing event in the development of the cutanenous lesions of bullous pemphigoid.

Autoantibodies↗

Dermatoleukodystrophy with neuroaxonal spheroids.

A Japanese brother and sister, the progeny of healthy parents, were born with thickened, wrinkled skin and died between the age of 2 and 3 years with a progressive cerebral disease characterized by generalized mental and motor impairment. Postmortem neuropathological studies disclosed a remarkable leukodystrophy in which multiple axonal spheroids were the outstanding feature. Ultrastructurally, the spheroids contained granules resembling ceroid-lipofuscin bodies. Similar granules were found in degenerating oligodendrocytes and in Schwann cells. The skin showed hypercellular and sclerotic features, suggestive of a genodermatosis. This combined neurologic and dermatologic syndrome, which, to our knowledge, has not hitherto been recognized, may well result from a genetically determined metabolic disorder, the nature of which still remains undisclosed.

Axons↗

Urticaria associated with acute viral hepatitis type B: studies of pathogenesis.

To determine whether skin deposition of circulating immune complexes contributes to prodromal urticaria of acute hepatitis B, we studied two patients with hepatitis B who presented with urticaria and fever. During the urticarial prodrome but not thereafter, we found activation of both classic and alternative complement pathways. Hepatitis B surface antigen (HBsAg)-antibody complexes were identified (by electron microscopy) in cryoprecipitates from both patients and IgG (by immunodiffusion) in cryoprecipitates of one patient during urticaria. Light and electron microscopy of involved urticarial skin revealed necrotizing venulitis in both patients. Immunofluorescence microscopy showed fibrin within involved cutaneous vessel walls in one patient and C3, IgM, and HBsAg, which were not detected in simultaneously obtained uninvolved skin, in both patients. Our findings suggest that deposition of circulating immune complexes containing HBsAg is important in the pathogenesis of urticaria associated with acute hepatitis B virus infection.

Adult↗

Cutaneous necrotizing venulitis: a sequential analysis of the morphological alterations occurring after mast cell degranulation in a patient with a unique syndrome.

An unusual patient, with dermal nodules, flexion contractures of the fingers and toes, cold-induced urticaria, dermographism and serum hypocomplementaemia, had necrotizing cutaneous venulitis underlying the spontaneous lesions. Since necrotizing cutaneous venulitis could be experimentally induced by the physical stimuli of cold or trauma, the time-course of histopathological events was documented in the skin of this patient. The histopathological alterations were studied in 1 micron thick, Epon-embedded skin biopsy specimens over an interval of 6 days. The early massive degranulation of the mast cells was followed by the sequential infiltration of neutrophilic, eosinophilic and basophilic polymorphonuclear leucocytes, by the development of venular endothelial cell necrosis and by the deposition of fibrin. The persistent serum hypocomplementaemia involved the classic activating and amplification pathways. It seems possible that the unusual combination of pathobiological processes involving the mast cells and the complement system in this patient has created a unique syndrome, in which venules are damaged and the sheaths of the extensor tendons of the hands and feet become affected in time.

Adult↗

Mannosidosis. New clinical presentation, enzyme studied, and carbohydrate analysis.

Mannosidosis is a rare inborn error of metabolism characterized by deficiency of the lysosomal enzyme alpha-mannosidase and widespread storage of complex carbohydrate, which is enriched in mannose. Two affected unrelated males, aged 6 and 26 years, are reported. Both had a nonprogressive encephalopathy with moderately severe mental retardation. The older patient showed several unique features, including massive gingival hyperplasia associated with histiocytes containing large amounts of a material with the staining characteristics of glycoprotein. The best determinant of mannose storage proved to be the ratio of mannose to other carbohydrates in urinary polysaccharides. The enzyme deficiency in this disease is most convincingly demonstrated at pH values below 4.0. The ability of zinc to activate the mutant enzyme in vitro offers a possible mode of therapy for this disease. Retarded individuals with a Hurler-like appearance and gum hyperplasia of unknown cause should be screened for alpha-mannosidase deficiency.

Adult↗

Multiple granulocytic tumors of the skin: report of six cases of myelogenous leukemia with initial manifestations in the skin.

The clinical and pathologic findings in six patients with myelogenous leukemia presenting initially as multiple granulocytic tumors of the skin were reviewed. The skin of the trunk was most commonly involved with multiple, confluent erythematous plaques and soft, tender, non-ulcerated, violaceous nodules. Two patients had been treated for malignant lymphoma eight and nine years prior to the onset of skin lesions (Hodgkin's disease and nodular lymphocytic lymphoma, respectively), and cutaneous granulocytic leukemia developed in sites of irradiated skin. The skin biopsies in all cases were originally misinterpreted by the pathologist as malignant lymphoma and the correct diagnosis of granulocytic leukemia was not established in any of the cases until overt extracutaneous involvement was detected. The interval in the six patients from skin biopsy to definite involvement of blood and bone marrow by acute granulocytic leukemia ranged from three weeks to six months with a mean interval of 3.8 months. The mean duration of survival from the diagnosis of extracutaneous dissemination was 12.7 months (range of three months to two and one-half years). Poorly differentiated myelogenous leukemia was demonstrated at postmortem examination in all cases. Cytochemical stains of formalin-fixed, paraffin-embedded tissues confirmed the granulocytic origin of the neoplasm: leukemic cells in skin biopsies, bone marrow aspirates, and autopsy specimens contained abundant naphthol AS-D chloracetate esterase. The findings indicate that granulocytic leukemia may rarely present with skin tumors as the original manifestation of the disease. Recognition of the distinctive clinical, histopathologic, and enzyme histochemical features of the lesion provide a basis for distinguishing granulocytic sarcoma of the skin from mycosis fungoides and other cutaneous malignant lymphomas.

Acetates↗

Early detection of malignant melanoma.

Case examination of the skin is the first and foremost tool in the detection of skin cancer. Early diagnosis of malignant melanoma is possible with appreciation of certain color changes, surface changes, and border changes in pigmented lesions. Emphasis is placed upon these criteria for diagnosis and other associated phenomena that may lead to suspicion of early malignant melanoma.

Diagnosis, Differential↗

Malignant lymphoma of the skin: a clinicopathologic study of lymphoma other than mycosis fungoides.

The clinical and histopathologic findings in 25 cases of malignant lymphoma of the skin other than mycosis fungoides were reviewed. All patients had skin lesions as a primary manifestation of the disorder, and none had histopathologic evidence of extracutaneous involvement at the time of skin biopsy. The majority of patients had solitary nodules involving the skin of the head and neck region. Twenty-two of the skin biopsy specimens were interpreted as lymphocytic lymphoma, well or poorly differentiated, nodular or diffuse. Only three cases of histiocytic lymphoma (reticulum cell sarcoma) were encountered, and there were no cases of Hodgkin's disease of the skin. Twenty-two patients (88%) subsequently developed extracutaneous lymphoma: the interval from the occurrence of apparently localized skin lesions to involvement of lymph nodes and/or viscera ranged from 6 months of 5 years (mean duration of 21 months). Sixteen patients (64%) died of disseminated lymphoma, with survivals that ranged from 8 months to 12 years (mean survival of 3.7 years). Only three patients survived without disease for greater than 1 year. There was no definite relationship between either the histologic subtype of the tumor or the mode of therapy and prognosis. The patholoic findings indicate that a definite diagnosis of malignant lymphoma can be made by skin biopsy in patients with disease apparently confimed to the skin. Careful, detailed examination of the skin biopsy specimen provides a basis for distinguishing malignant lymphoma from cutaneous lymphoid hyperplasia. The clinical findings and survival data support the conclusion that malignant lymphoma with skin lesions as a primary manifestation almost invariably disseminates to extracutaneous organs and usually has a fatal outcome.

Aged↗

Two distinct cellular patterns in cutaneous necrotizing angiitis.

Two distinct cellular patterns of necrotizing angiitis involving venules in skin of patients with clinically identical cutaneous lesions were appreciated by the 1 -mum-thick section technique. In those individuals with serum hypocomplementemia, there was a perivenular inflitrate composed predominantly of neutrophils with fibrin deposition and nuclear debris. In patients with normal serum complement levels, in addition to an infiltrate of neutrophils and fibrin deposition, perivenular lymphocytes in various stages of activation were prominent. In both patterns the venules and not the arterioles were affected, mast cells exhibited various degrees of hypogranulation, and basophils and eosinophils were recognized only rarely. Lesions of different clinical age obtained from one hypocomplelmentemic patient and one normocomplementemic patient exhibited consistent cellular patterns, as did a single crop of lesions biopsied twice, 24 hr apart, in a patient with hypocomplementemia. No patient with hypocomplementemia became normocomplementemic or vice versa with persistence of lesions.

Adult↗

Morphology of delayed-type hypersensitivity reactions in man.

The new morphologic findings reviewed here substantially alter prevalent conceptions of delayed hypersensitivity as a simple cutaneous infiltration of lymphocytes and macrophages. By assigning an integral role of basophils, mast cells, the microvasculature, and the clotting system, the findings have far-reaching implications for an understanding of these clinically important reactions. Morphologic observations, of course, represent only a first step, a foundation on which subsequent immunologic, physiologic, and biochemical experiments can build. Much further work will be required to interrelate these new findings and to integrate them with older observations into a coherent sequence of events which can explain the pathogenesis of cell-mediated reactions. A preliminary attempt in this direction, based on present, rather incomplete information, is presented in Figure 8 as a basis for further investigation.

Anaphylaxis↗

Morphology of delayed-type hypersensitivity reactions in man. II. Ultrastructural alterations affecting the microvasculature and the tissue mast cells.

Profound alterations in the dermal microvasculature and the closely related fixed tissue mast cells were observed in allergic contact dermatitis reactions to dinitrochlorobenzene and urushiol in man. The vascular changes were of two types. The superficial capillary venule, a distinct anatomical and functional vessel system in the dermal papillae, developed interendothelial cell gaps, maximal at 3 days after skin test, which very likely were responsible for locally increased vascular permeability and consequent dermal edema. The products of degranulating tissue mast cells and infiltrating basophils may have been partly responsible for these changes. By contrast, vessels of the superficial venular plexus, oriented parallel to the cutaneous surface at the junction of the papillary and reticular dermis, were the site of diapedesis and perivascular cuffing by lymphocytes and other inflammatory cells. The superficial venular plexus vessels exhibited striking endothelial cell and pericyte hypertrophy, occasional necrosis of endothelial cells, endothelial cell mitoses, and an extensive and progressive laying down of new and abnormally disposed basal lamina. These changes, somewhat slower to develop than those affecting the superficial capillary venule, were present in all biopsies taken at 3 days or later and were accompanied by mast cell mitoses and the appearance of immature dermal mast cells. The basal lamina-alterations persisted and evolved for at least several weeks. The mechanisms initiating these vessel and mast cell changes have not been identified, but circumstantial evidence suggests that lymphocytes or their products or both may have been responsible.

Administration, Topical↗

Degranulation of basophilic leukocytes in allergic contact dermatitis reactions in man.

Basophilic leukocytes participating in allergic contact dermatitis in man underwent progressive degranulation over the course of several days after skin test. Less than 10% of basophils were degranulated in 24-hr reactions, but more than 60% were degranulated by 72hr. In electron microscopic individual basophil granules developed looser packing of particles by finely granular material, and eventual loss of all visible granule contents, changes that were progressive between 2- and 3-day reactions.

Adolescent↗

Bullous dermatosis of hemodialysis.

Five patients with chronic renal failure who were undergoing maintenance hemodialysis developed a self-limited bullous dermatosis restricted to light exposed areas, primarily involving the dorsa of the hands. Porphyrin levels and phototesting were normal, but histologic sections of the bullae showed thickening of venule walls, hypogranulated mast cells, and perivenular deposition of immunoglobulins. This combination of features has not previously been described and may reflect a pathologic process unique to chronic hemodialysis.

Adult↗

The clinical diagnosis of malignant melanoma.

The diagnosis of malignant melanoma thus rests upon an appreciation of sometimes subtle but definite signs detectable by careful observation of color, border, and surface of the lesions. Differential diagnosis lies among several cutaneous lesions, neoplastic and nonneoplastic. At times the lesions that are most difficult to distinguish from malignant melanomas are certain pigmented basal cell carcinomas, thrombosed hemangiomas, and certain types of moles. An attempt has been made in this review to describe and illustrate those features of pigmented lesions that are most helpful in diagnosis.

Basal Cell Carcinoma↗