Destructive granuloma annulare of the skin and underlying soft tissues--report of two cases.

Two cases of extensive cutaneous granuloma annulare (GA) associated with severe deformity and impairment of function in the involved extremity are described. In the first patient a mutilating, destructive arthritic condition and infiltrative oedema of upper extremities developed over the years along with florid disseminated GA of the tendons and overlying skin. In the second patient disseminated GA of one lower extremity resulted in diffuse induration and chronic lymphoedema. In both cases, histology showed palisading granulomas typical of GA at all levels of the dermis, subcutaneous tissues, fascia, and synovium. The unique clinical features of GA in both presented cases emphasize the local destructive potential and, as yet, poorly understood progression of GA to a soft-tissue disease.

Clinicopathologic spectrum of cutaneous manifestations in systemic follicular lymphoma. A study of 11 patients.

Follicular lymphoma is rarely diagnosed on the basis of only a cutaneous biopsy. Eleven patients with primary follicular lymphoma of lymph nodes who developed skin lesions were studied. Skin lesions involved the scalp, head and neck, trunk, and buttocks and were small cleaved cell type in four cases, large cell type in three cases, and mixed type in four cases. The follicular pattern with a bottom-heavy distribution was identified in only six of the 11 cases. One case showed a nodular, perivascular pattern in the deep dermis and subcutaneous tissue. Four cases were characterized by a diffuse pattern of lymphocytic infiltrate. One patient with a diffuse pattern had an isolated subepidermal band of lymphoma cells representing primary cutaneous T-cell lymphoma. Cutaneous involvement by lymphoma previously diagnosed as low-grade (follicular growth pattern) transformed to higher grade disease in five of ten asynchronous cases. The 5-year survival rate was 60% among the transformed cases and 100% among the nontransformed cases. Extranodal cutaneous involvement in follicular lymphoma occurred in 3.8% of cases. The correct histologic diagnosis in a skin biopsy specimen can be established in cases with a follicular pattern (60%) with conventional histologic criteria such as redundancy of follicles, uniformity of follicular center cell composition, lack of interspersed phagocytic histiocytes, and absence of immunosecretory cellular elements such as plasma cells and immunoblasts.

Generalized granuloma annulare: histopathology and immunopathology. Systematic review of 100 cases and comparison with localized granuloma annulare.

Some form of collagen alteration (necrobiosis) was observed in 53% of patients with generalized granuloma annulare and in 79% of patients with localized granuloma annulare. Fragmentation of collagen bundles was the most common single type of collagen abnormality in both groups. Collagen sclerosis, accompanied by a strong palisading pattern of histiocytes, was more frequent in localized granuloma annulare. Results of microdroplet lipid staining were positive in 80% of annulare cases and 39.3% of nonannulare cases of generalized granuloma annulare. Inflammatory cells were confined to peripheral perivascular lymphocytes; bandlike granuloma below the epidermis was observed. Positive results of direct immunofluorescence tests in 12 of 23 patients with generalized granuloma annulare suggested that fibrin deposition in areas of altered collagen is less frequent in the generalized than in the localized form, a possible reflection of the lower rate of histologic collagen alteration in that group. Lymphohistiocytic granuloma with various degrees of collagen degeneration, microdroplet lipid accumulation, and mucin deposition form the basic pathologic description of granuloma annulare.

Generalized granuloma annulare: clinical and laboratory findings in 100 patients.

Clinical and laboratory records of 100 biopsy-proved cases of generalized granuloma annulare seen at the Mayo Clinic between 1966 and 1986 were reviewed. The skin eruption involved predominantly annular lesions in 67 patients and predominantly nonannular papules in 33. The ratio of female-to-male patients was 2.9:1 in the annular group and 1.4:1 in the nonannular group. The mean age at onset was 51.7 years. The eruption was symptomatic in 34 patients, and specific precipitating factors could be implicated in 16 patients. No consistently associated systemic disorders were identified. Diabetes mellitus was diagnosed in 21% of our referral group of generalized granuloma annulare cases, compared with 9.7% in 1350 cases of localized granuloma annulare and 10.3% in 1383 cases of all forms of granuloma annulare seen at the Mayo Clinic in the same period. Serum lipid abnormalities were more common in the generalized annular group. Follow-up data indicated a chronic, relapsing course in most patients.

Granulomatous reactions in mycosis fungoides.

Granulomatous reaction characterized by the formation of noncaseating accumulations of epithelioid histiocytes and multinucleated giant cells of the foreign-body type is a rare, poorly understood, and generally ignored phenomenon seen in various types of lymphoma. Its presence in cutaneous infiltrates of mycosis fungoides is equally unusual, but some favorable prognostic significance has been ascribed to it previously. In this paper, four patients with typical mycosis fungoides and granulomas demonstrated histologically in their cutaneous infiltrates are presented. All four died of disseminated disease with evidence of central nervous system involvement in three of them. These clinical histories lend no support to the notion that granulomatous mycosis fungoides is a benign variant of this lymphoma. Relevant literature is reviewed and discussed.

Large cell lymphocytoma: follow-up, immunopathology studies, and comparison to cutaneous follicular and Crosti lymphoma.

Thirteen cases of large cell lymphocytoma are reviewed. All cases are alive or dead free of lymphoma. The histology and immunoreactivity of B cells. Peripheral or small central masses of T cells are present. The microscopic and clinical findings suggest that this tumor is a benign lymphadenoid proliferation which is readily treated by X-ray or surgery.

Squamous cell carcinoma complicating late chronic discoid lupus erythematosus.

Two cases of squamous cell carcinoma developing in lesions of chronic cutaneous discoid lupus erythematosus are presented. One of the patients was white and the other was black. The squamous cell carcinoma in the black patient proved to be rapidly metastatic and eventually fatal. The white patient developed seven squamous cell carcinomas over 8 years with no evidence of metastatic spread. The role of ultraviolet light in inducing skin cancer in these patients is discussed.

Dysplastic nevus syndrome: association with multiple primary neoplasms.

A 65-year-old white man with dysplastic nevus syndrome is presented. The patient also developed an extramammary Paget's disease of the scrotum, two malignant melanomas of the skin of the arm and abdomen, two squamous cell carcinomas in the mouth, and several benign tumors such as lentigo maligna, dermatofibroma, and a cavernous hemangioma. Besides the well-established tendency of patients with the dysplastic nevus syndrome to develop malignant melanomas of the skin, their possible propensity to develop other primary malignant neoplasms is discussed.

Skin cancer caused by grenz rays.

A 30-year-old woman developed chronic radiodermatitis and five squamous cell carcinomas within 7 years following a 16-year period of repeated grenz irradiations given to her psoriasis. The estimated cumulative dose of grenz radiation was approximately 3,000 rads (r) to each treated area. This case, illustrating a rather underestimated carcinogenic potential of grenz rays, is interpreted in light of the available literature on the subject. The technical bases of grenz ray therapy are also briefly reviewed.

Chromosome changes in mycosis fungoides in an XYY male.

A 32-year-old white male was diagnosed as having mycosis fungoides in 1976; bone marrow biopsy and aspiration in August 1984 revealed infiltration with neoplastic cells. Cytogenetic analysis of the cells from the bone marrow specimen showed that 48 of 50 metaphases contained an extra Y chromosome (i.e., 47,XYY). The remaining two cells were hypotetraploid and hyperpentaploid, respectively, with a common marker derived from chromosome #2. The metaphases obtained by PHA stimulation of peripheral blood cells showed a 47,XYY pattern. An interleukin 2 (IL-2) dependent T-cell line was established from the patient's blood mononuclear cells; all metaphases of this line had an extra Y chromosome. Thus, this case is one of a mycosis fungoides developing in an XYY male.

Paget's disease of the breast presenting as a cutaneous horn.

A 67-year-old woman developed a cutaneous horn on the nipple of her right breast. Biopsy of the skin underlying the horn disclosed Paget's disease of the breast. An intraductal adenocarcinoma of the same breast was found on mastectomy. High index of suspicion is mandatory in evaluating all nipple lesions.

Breast carcinoma metastatic to eyelids: case report and review of the literature.

Violaceous, indurated plaques around both eyes were found to be cutaneous metastases and the initial clinical presentation of a lobular carcinoma of the breast in an 80-year-old woman. Available literature indicates that breast carcinoma is the most common metastatic tumor of the eyelid and the onset of a palpebral mass may precede the diagnosis of the primary tumor in the breast.

Unusual clinical presentation of epidermotropic cutaneous lymphoma. Small hypopigmented macules.

A 35-year-old black woman developed numerous vitiligo-like small hypopigmented macules on the upper and lower extremities. Histologically the lesions were consistent with epidermotropic mycosis fungoides or pagetoid reticulosis. The patient is presented because of a clinical picture unusual for either of the above microscopic diagnoses.

In vitro effects of enzymes of polymorphonuclear leukocytes on the antigenicity of stratum corneum.

Anti-stratum corneum (SC) antibodies of human serum bind in vitro to the SC of frozen sections of normal skin of psoriatic patients and of healthy controls. Pretreatment of skin sections with selected dilutions of acid extracts from polymorphonuclear leukocytes (PMN) prior to the incubation with serum containing anti-SC autoantibodies enhances this binding in comparison with binding to untreated sections. Pretreatment of at least some specimens with higher concentrations of the same PMN extracts brings about a reduction in their reactivity with anti-SC autoantibodies. These findings indicate that enzymes of PMN are capable of altering SC antigens by first increasing and then decreasing their reactivity with SC autoantibodies.

Demonstration of allospecific differences in human stratum corneum autoantibodies by blocking immunofluorescence.

Stratum corneum antibody titers of six normal human sera were determined by indirect immunofluorescence on three different epidermal substrates with and without preincubation of the substrates with one monkey serum. In three out of six human sera the reaction of stratum corneum antibodies was inhibited on all three substrates, in one serum the inhibition was noted on two out of three substrates and no effect was observed in two sera. These findings provide further evidence for the existence of allospecific stratum corneum antibodies in human sera and for the presence of both species-specific and species-nonspecific glycoprotein stratum corneum antigens in human epidermis.

A standardized method of detecting antibodies to extractable nuclear antigens (RNP and Sm) by gel precipitation.

Because of the importance of the detection of antibodies to RNP and Sm in the diagnosis of mixed connective tissue disease, systemic lupus erythematosus and certain forms of systemic sclerosis, the various factors which influence the sensitivity of the gel precipitation method for the detection of these antibodies were investigated. The agarose concentration, thickness, well sizes and distance between wells influence the sensitivity of the precipitin reactions. Suitable conditions for a sensitive and reproducible test system are specified. Because of variations in the antigenic composition of extractable nuclear antigen preparations made by different methods and from different tissue sources, a two-dimensional "chessboard titration" using serial twofold dilutions of a reference serum to test doubling dilutions of antigen preparations is recommended for standardizing different lots of antigen. Using the above-mentioned standardized agarose plates and appropriate reference serum with anti-Sm and/or anti-RNP antibodies in a chessboard titration, it is recommended that acceptable use dilution of antigen preparation be two doubling dilutions before reaching an endpoint. The reference sera selected should be compared to US reference standards supplied by the Center for Disease Control.

Studies in immunodermatology. X. Detection of glycoprotein- and carbohydrate-type stratum corneum antigens by immunofluorescence: conversion effects of enzymes and trauma.

Normal human sera contain stratum corneum (SC) antibodies to two biochemically distinct antigens of normal skin as demonstrated by indirect immunofluorescence (IF) staining with selectively absorbed sera. Absorption of normal human sera with ground callus removed the SC antibodies reactive with the horny layer of normal skin but did not affect the SC antibody titers on cut edges of trypsin-digested callus or lesions of monkey skin induced by scratching. Conversely, absorption of the same sera with a carbohydrate-type SC antigen reduced SC antibody titers on the cut edges of trypsin-digested callus and on lesions of monkey skin induced by scratching but did not alter titers of SC antibodies on normal skin sections.

Studies in immunodermatology. XI. Demonstration of allospecificity of stratum corneum antibodies and antigens by indirect immunofluorescence.

The presence of allospecificities of stratum corneum (SC) antibodies was suggested by the observation that 5 normal human sera tested by indirect immunofluorescence (IF) on 5 unrelated normal human skins yielded variable titers on some skin specimens. Titers of SC antibodies of normal sera absorbed with ground callus collected from one donor in IF tests on 5 unrelated normal human skin specimens provided further evidence that allospecific SC antibodies are present in human sera and that SC antigens in different human skins are not identical. Since SC antibodies in human sera do not give significantly different titers on autologous skin substrates as compared to homologous ones, they behave both like auto- and alloantibodies.