Herpes simplex vegetans: atypical genital herpes infection in a patient with common variable immunodeficiency.

Large papillomatous lesions clinically resembling verrucous carcinoma may be caused by viruses other than human papillomavirus. We report a case of recurrent vegetations covering the entire vulva in a pregnant patient with common variable immunodeficiency. Herpes simplex virus was recovered from these lesions. The patient did not respond to intravenous acyclovir, but her lesions dramatically healed with two courses of intravenous foscarnet. Repeated biopsies may prove necessary in cases such as this to ensure proper diagnoses.

Early presentation of pityriasis rubra pilaris.

Pityriasis rubra pilaris (PRP), a disorder of epidermal proliferation and altered keratinization, typically first appears as a scaly, erythematous patch on the upper portion of the body. Its initial appearance is nonspecific and may be confused with other common dermatoses. Subtle clinical findings and histologic changes in the early stage of PRP are helpful in the early diagnosis of this condition. We describe two cases to illustrate the initial manifestations of PRP and review the literature, emphasizing its early presentation and treatment.

Cutaneous histopathology of Rocky Mountain spotted fever.

The dermatologic diagnosis of Rocky Mountain spotted fever (RMSF) is often presumptive; the clinical presentation includes skin rash and febrile illness with or without a clear history of tick bite. The characteristic cutaneous manifestations include a generalized skin eruption with purpuric, blanching or non-blanching macules and papules usually involving the extremities. Although skin biopsies are often performed to confirm the diagnosis, the spectrum of cutaneous histopathology in RMSF has not been well described. We studied a series of 26 cases of RMSF, of which 10 were surgical specimens and 16 were autopsies. The microscopic changes were correlated with the duration of illness. The main histopathologic feature was lymphohistiocytic capillaritis and venulitis with extravasation of erythrocytes, edema, predominantly perivascular and some interstitial infiltrate. Leukocytoclastic vasculitis (LCV) with neutrophilic infiltrate and nuclear dust was seen in 11 of 15 (73%) specimens from involved skin. These lesions with LCV also showed notable epidermal change including basal layer vacuolar degeneration with mild dermoepidermal interface lymphocytic exocytosis. Six lesions with LCV displayed focal fibrin thrombi and capillary wall necrosis. Apoptotic keratinocytes were noted in 3 lesions with LCV. Subepidermal blister was observed in the skin lesion of an autopsied patient with LCV changes. Another lesion of a fatal case with LCV also contained features of acute neutrophilic eccrine hidradenitis. Focal small nerve twig inflammation was noted in a third autopsy case with LCV. Plasma cells were seen in 6 of 34 specimens (18%); and eosinophils were observed in 3 (9%). The subcutaneous fat contained a mild perivascular inflammation and one case revealed focal lobular neutrophilic inflammation. Immunohistologic (IH) staining using polyclonal rabbit anti-Rickettsia rickettsii demonstrated positive staining of the organisms in the affected endothelial cells in all 12 cases tested. The cutaneous histopathology of RMSF is caused by endothelial damage by the rickettsial organisms which elicit an initial lymphohistiocytic small vessel vasculitis with progression to LCV. The vasculitis in RMSF is, therefore, considered to be a form of septic vasculitis.

Tinea caput medusa: an unusual presentation of Trichophyton mentagrophytes on the scalp.

Tinea capitis has a wide variety of clinical presentations in adolescents and adults. However, the occurrence of fingerlike projections in the scalp has not been previously described. A 14-year-old girl presented with a one-year history of a painful scalp mass. Debridement of this mass revealed slender papillomatous growths resembling those seen in elephantiasis nostras verrucosa. A fungal culture grew Trichophyton mentagrophytes. We describe the first case of this unusual clinical variant of tinea capitis and hypothesize on its pathophysiological basis.

Cutaneous malacoplakia: a report of two cases and review of the literature.

Malacoplakia, an inflammatory disease characterized by accumulations of phagocytic macrophages, occurs primarily in immunocompromised individuals. Cutaneous involvement is rare. Two men, each with a renal allograft, had expanding nodules on the temple and perianal area (case 1) and perianal, inguinal, and scrotal skin (case 2). Lesions resolved after combined surgical and antibiotic therapy. Histopathologic examination showed dense infiltration with large phagocytic macrophages containing round, concentric, laminar Von Kossa stain-positive inclusion bodies. Histiocytes had positive results for CD 68, lysozyme, and alpha 1-antitrypsin. Electron microscopic examination demonstrated rare intracytoplasmic inclusion bodies with concentric electron-dense laminations of calcium (Michaelis-Gutmann bodies.) Cutaneous malacoplakia should be considered in the differential diagnosis of nodules or draining ulcers, particularly in immunocompromised patients. Because Michaelis-Gutmann bodies are difficult to identify, specimens should be evaluated for cutaneous malacoplakia by immunohistochemical or electron microscopic means.

Cutaneous eruptions from suramin. A clinical and histopathologic study of 60 patients.

BACKGROUND AND DESIGN: During a trial of suramin for advanced solid tumors, a high rate of cutaneous adverse reactions was observed. We present a prospective study, describing the clinical, histopathologic, histochemical, and immunochemical findings of the cutaneous reactions observed in 60 patients treated with suramin. RESULTS: Forty-nine (82%) of the 60 patients studied experienced at least one cutaneous reaction attributable to suramin therapy. Although morbilliform reactions predominated, a wide variety of eruptions was observed. Most reactions occurred within the first 24 hours of therapy and were self-limited despite continued drug infusion. Distinctive cutaneous findings included scaling erythematous papules (suramin keratoses) and a predilection of many eruptions for previously sun-exposed areas. Six patients experienced severe cutaneous reactions, but no patient permanently withdrew from therapy because of cutaneous toxic reactions. Common histopathologic findings included hyperkeratosis, parakeratosis, spongiosis, acanthosis, exocytosis, apoptosis, a perivascular lymphohistiocytic infiltrate, upper dermal edema, and increased dermal mucin. Staining with S100 antigen was markedly positive in several specimens. Only trace amounts of suramin were detected in skin samples tested with high-pressure liquid chromatography. CONCLUSIONS: The incidence of cutaneous toxic reactions from suramin greatly exceeds that seen with other medications. A wide spectrum of skin manifestations were observed, including suramin keratoses and UV recall, although serious reactions were infrequent. Cutaneous toxic reactions neither predicted nor correlated with other toxic reactions from suramin. Suramin may soon become more widely used; practitioners should be aware of the high incidence and wide spectrum of cutaneous toxic reactions to this drug.

Quantitative image analysis of p53 protein accumulation in keratoacanthomas.

Keratoacanthomas are benign skin tumors that grow rapidly but eventually regress. They occur most commonly in sun-exposed skin and are histologically remarkably similar to squamous cancers. Since mutations of the p53 tumor suppressor gene are found frequently in cutaneous squamous cell carcinomas, we hypothesized that p53 mutations might contribute to the development of keratoacanthomas. To address this question, we did p53 immunohistochemistry with a polyclonal rabbit antiserum, CM-1, that binds both mutant and wild-type p53 proteins. Although wild-type p53 protein degrades rapidly and is generally undetected by immunohistochemistry, mutant p53 protein has a longer half-life and accumulates to detectable levels. We tested 26 formalin-fixed keratoacanthomas and 4 normal skin biopsies. Positive nuclear staining was detected in 20 of 26 (77%) of the keratoacanthomas and in none of the normal skin samples. Nuclear staining occurred in the outermost layer of the neoplasms and not in the keratin-filled central cores. Since nuclear p53 protein within a cutaneous squamous cell carcinoma usually correlates with missense mutation, these data suggest that p53 mutations contribute to the development of this benign neoplasm. The histologic similarity to squamous cell carcinoma and the accumulation of p53 protein suggest progression toward malignancy, but the invariable regression of these tumors suggests an arrest at some point in multistage carcinogenesis. If this model is correct, then genetic analysis of keratoacanthomas may provide clues to the later stages of squamous carcinogenesis including local invasion and metastasis.

Cutaneous metastasis from a parotid adenocarcinoma. Report of a case with immunohistochemical findings and review of the literature.

We present a rare case of metastatic adenocarcinoma of the parotid gland to the skin. Reviewing the histologic features of the primary parotid gland and comparing the microscopic sections and immunohistochemical studies, we concluded the skin tumor to be metastases from the parotid adenocarcinoma. By histologic examination alone, it is difficult to distinguish an eccrine sweat gland carcinoma from a metastatic carcinoma of the salivary gland. Immunohistochemical analysis may not be conclusive. Therefore, clinical history and clinicopathologic correlation are essential in arriving at an accurate diagnosis in these cases.

Multiple eruptive dermatofibromas in an HIV-positive man.

Multiple dermatofibromas (DFs) may occur in association with altered immunity, including systemic lupus erythematosus and iatrogenic immunosuppression. We report a case of multiple eruptive DFs which occurred in a patient positive for human immunodeficiency virus (HIV). The association of eruptive DFs and HIV infection has not been previously reported. The mechanism for the development of DFs in the setting of immune disturbance remains unclear. In the setting of HIV infection, DFs may clinically mimic Kaposi's sarcoma.

Eccrine angiomatous hamartoma (nevus): immunohistochemical findings and review of the literature.

Eccrine angiomatous hamartoma (nevus) is a rare form of congenital tumorous malformation with proliferation of eccrine secretory coils and ducts, surrounding capillary angiomatous channels and occasionally other minor elements. To date, there have been only about 24 cases reported in the literature. We report an additional case with more detailed description of the microscopic findings, including immunohistochemical observations. The patient was a 28-year-old female who presented with painless, flesh- to reddish brown-colored, violaceous or bluish subcutaneous nodules on the extremities and trunk. The tumors did not show sweating following exertion. The histologic features were comparable to the previously reported cases. The hamartomatous eccrine sweat glands and ducts and a few apocrine glands demonstrated qualitatively diminished antigens commonly found in the eccrine sweat apparatuses, such as carcinoembryonic antigen (CEA) and S-100 protein. The findings of CD34, CD44, human nerve growth factor receptor and Ulex europaeus antigens have not been previously reported. The histologic features suggested a "hamartomatous" growth rather than a true neoplastic process.

Primary cutaneous CD30-positive anaplastic large cell lymphoma. Report of 27 cases.

The clinical, morphological and immunohistochemical features of 27 patients with anaplastic large cell lymphoma (ALCL) of CD30-positive type, with cutaneous lesions as the sole initial clinical manifestation, were analyzed. The neoplasm presented as solitary or multiple, usually ulcerated skin lesions, affecting predominantly elderly patients (median age: 67 years) with a male preponderance (male to female ratio of 6:1). In most patients, there was an excellent response to chemotherapy. The cardinal histological features included diffuse dermal and subcutaneous infiltration by large, anaplastic tumor cells, all or nearly all of which showed diffuse, strong membrane staining and frequently a paranuclear, dot-like reaction with the CD30 marker (Ber-H2). Epidermal ulceration, pseudo-epitheliomatous hyperplasia and dermal vascular proliferation were also observed.

Balloon cell malignant melanoma of the skin. A clinicopathologic study of 34 cases with histochemical, immunohistochemical, and ultrastructural observations.

Balloon cell malignant melanoma (BCMM) is a rare histologic variant of malignant melanoma (MM). Thirty-four patients with BCMM from the files of the Armed Forces Institute of Pathology (AFIP) were studied by means of clinicopathologic correlation and histochemical, immunohistochemical, and ultrastructural methods to better define this entity. The cytoplasmic features of the balloon cells observed in BCMM resemble those noticed in balloon cell nevus (BCN), but the presence of nuclear pleomorphism, atypia, and mitoses and the absence of intervening stroma help distinguish BCMM. The cells also show many histochemical, immunochemical, and ultrastructural features of conventional melanoma cells. Although it is generally believed that balloon melanoma cells represent a degenerative change, the immunohistochemical and electron microscopic findings suggest that the balloon tumor cells are most likely metabolically active melanocytic cells. Microscopically, BCMM also must be differentiated from other clear cell tumors such as clear cell sarcoma (MM of soft parts), hibernoma, xanthoma, sebaceous neoplasms, metastatic renal cell carcinoma, (malignant) clear cell acrospiroma, (malignant) granular cell tumor, granular (clear) cell basal cell carcinoma, clear cell syringoma, and atypical fibroxanthoma. The prognosis of BCMM usually correlates with the tumor thickness similar to that in other histologic types of cutaneous MM. Nineteen (57.5%) of 33 patients with adequate follow-up information died of disseminated tumors from 2 months to 12 years after the initial treatment. Six (18.2%) patients developed local recurrences: four of these patients died of metastasis and two were alive with metastatic tumor at last contact. Five (15.2%) patients were alive with metastatic tumors, and seven (21.2%) were alive without evidence of disease at last contact. Recognition of BCMM is important because of its malignant biologic behavior.

Eccrine spiradenoma occurring in infancy mimicking mesenchymal tumor.

Eccrine spiradenoma (ES) rarely (less than 1%) occurs in infancy. These tumors differ from the conventional ES by the presence of superficial dermal nodules which display a less distinct two-cell pattern of immature adnexal epithelial cells and rarely ductule formation. These tumors may be mistaken for mesenchymal neoplasms involving the skin and subcutis of infants and young adults. Recognition of the histopathologic features and immunostains are required to make a definite diagnosis. We describe 2 cases of ES occurring in patients younger than one year. Detailed histopathologic and histochemical differential features of these tumors and mesenchymal neoplasms of the skin and subcutis commonly occurring in infants and young adults are discussed. The biologic behavior of infantile ES is benign, but complete excision is recommended to prevent recurrence. We speculate that these tumors may represent congenital hamartomatous growths.

Familial multiple eccrine spiradenomas with cylindromatous features associated with epithelioma adenoides cysticum of Brooke.

Four cases of rare familial multiple eccrine spiradenomas showing features of dermal cylindromas and associated with epithelioma adenoides cysticum of Brooke are reported. Skin biopsy specimens were obtained from three generations of this family and routine histochemical and immunoperoxidase stains were used. The eldest affected family member had multiple disfiguring facial and scalp tumors, which precipitated episodes of depression. Unlike other cutaneous genetic disorders, such as neurofibromatosis and tuberous sclerosis, the cutaneous adnexal tumors occurring in these patients continue to erupt and grow during their lifetimes.

The nature of hyaline (eosinophilic) globules and vascular slits of Kaposi's sarcoma.

Ultrastructural studies of Kaposi's sarcoma (KS) from skin biopsies of 24 patients (eight with acquired immunodeficiency syndrome (AIDS) and 16 without) were performed to delineate the nature of hyaline globules and vascular slits. These structures have been regarded as one of the important criteria for the recognition of KS under light microscopy. Histochemical and immunochemical studies were also performed to correlate with the electron microscopic (EM) observations. The most remarkable EM findings of KS were the intracytoplasmic lumen formation and erythrophagocytic activities of the neoplastic cells, particularly in the mature nodular, or neoplastic stage. The spindle-shaped or ovoid neoplastic cells frequently contained one to several intact and fragmented red blood cells. The intracellular and extravasated erythrocytes were often arranged in single files, giving these vascular slits an elongated appearance on longitudinal sections. The phagocytic activities of the neoplastic cells were demonstrated by the presence of membrane-bound lysosomes containing phagocytized erythrocytes and their partially digested forms (erythrophagosomes) adjacent to pinocytotic vesicles, prominent rough endoplasmic reticulum, and Golgi apparatus, as well as scattered, small, membrane-bound lysosomal granules, some of which were attached to the erythrophagosomes. The erythrophagosomes underwent various stages of disintegration. The partially digested red cells varied from 0.4 to 10 microns in diameter. The results of histochemical and immunochemical findings also strongly suggested that erythrophagosomes were most likely the hyaline globules (bodies) seen in light microscopy. The exact mechanism of erythrophagocytosis is uncertain. However, its consequences, erythrophagosomes, and intracytoplasmic lumen formation, particularly in the nodular or neoplastic stage in patients with and without AIDS, are among the important histologic features of KS.

Focal acantholytic dyskeratosis occurring in pityriasis rubra pilaris.

Focal acantholytic dyskeratosis (FAD) is a distinctive histologic pattern characterized by suprabasilar clefts surrounding dermal papillae (villi), acantholytic and dyskeratotic cells at all levels of the epidermis, hyperkeratosis, and parakeratosis. The features of FAD are typically seen in Darier's disease, warty dyskeratoma, and transient acantholytic dermatosis; they are also present in a variety of cutaneous neoplastic and nonneoplastic lesions. FAD, however, has not been previously described in lesions of inflammatory dermatoses. We report a case of FAD occurring in lesions of pityriasis rubra pilaris (PRP). To the best of our knowledge, this is the first reported case of this kind. We also review the pertinent literature.

Solitary cutaneous plexiform neurilemmoma (schwannoma): a clinicopathologic, immunohistochemical, and ultrastructural study of 11 cases.

Plexiform neurilemmoma (PN) is a rare benign peripheral nerve sheath tumor. The tumor is an uncommon nodular variant of schwannoma. Eleven cases of cutaneous plexiform neurilemmoma (CPN) were studied by clinicopathologic correlation, immunohistochemistry, and electron microscopy. The patients' ages ranged from 6 to 80 yr; the median age was 37 yr. The tumors were presented as single, soft to rubbery, movable, nontender, and sometimes painful nodules ranging from 0.5 cm to 2.5 cm. in diameter. The lesions were most commonly located on the extremities. The overlying skin surface was intact. These tumors were not associated with von Recklinghausen's neurofibromatosis or neurilemmomatosis. On gross examination the cut surface of the tumors showed grayish-white to yellow or tan coloration and had a well-defined border, but there was no evidence of a plexiform growth pattern. The microscopic features were characterized by single or multiple well-circumscribed nodules of spindle-shaped tumor cells. The nuclei were irregular and elongated, and the cytoplasm was eosinophilic and fibrillary without distinct cytoplasmic borders. Nuclear palisading was prominent, and Verocay bodies were present. Mitotic figures were rare (fewer than 2 per 20 high-power fields). Bodian stain showed presence of nerve fibers at the periphery of the tumor. The adjacent tissue showed wavy, spindle-shaped cells and collagen fibers in a myxoid stroma rich in hyaluronic acid, a pattern reminiscent of neurofibroma. The tumor cells showed positive reactivity with anti-S-100 protein in both the nuclei and cytoplasm. Glial fibrillary acid protein was focally positive, and neuron-specific enolase was negative. Electron microscopy displayed features of Schwann cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Squamous-cell carcinoma of the scalp arising in lesions of discoid lupus erythematosus.

Squamous-cell carcinoma may arise in scars of chronic discoid lupus erythematosus. Although there have been 19 cases reported previously, detailed histopathologic features of this entity have not been recorded. We report a patient with extensive chronic discoid lupus erythematosus involving the scalp with subsequent development of multiple squamous-cell carcinomas. The tumors were locally aggressive with recurrences and invasion into the underlying skull and dura. The patient died of respiratory failure 4 1/2 years after initial surgical treatment. There was no clinical evidence of metastasis. Squamous carcinoma arising in discoid lupus erythematosus can be regarded as a low-grade carcinoma. Although about 20% of patients developed local recurrences and metastasis developed in about 30%, fatality occurred in only two patients (10.5%). Pertinent literature is reviewed, and the histopathologic findings, differential diagnosis, and biologic behavior of this tumor are discussed.

Kaposi's sarcoma in a renal transplant patient receiving cyclosporine.

A patient of Middle-Eastern descent developed Kaposi's sarcoma of the skin and lymph nodes after renal transplantation while receiving medical immunosuppression, including the use of cyclosporine. The clinical presentation of this patient resembled that of the HTLV-III-associated Kaposi's sarcoma. The tumors totally regressed seven weeks after cessation of immunotherapy. This case, along with other recently reported cases of Kaposi's sarcoma in postrenal transplant patients receiving cyclosporine, illustrates a rare complication of current immunosuppressive therapy.