Grace F. Kao

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‐positivc 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 sub‐cutaneous 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 ob‐served.

Cutaneous mucormycosis with subsequent visceral dissemination in a child with neutropenia: A case report and review of the pediatric literature

Primary cutaneous mucormycosis is a rare opportunistic fungal infection that is usually limited to the skin. We describe a primary cutaneous Rhizopus infection occurring at a site occluded by a sterile adhesive dressing in which the disease was viscerally disseminated at the time fo diagnosis. Mucormycosis should be considered in all ecthyma-like lesions in immunocompromised patients. It may be rapidly diagnosed by examination of hematoxylin-eosin and PAS-stained sections of the eschar base and a culture of a leading edge tissue aspirate. We review 21 cases of primary cutaneous mucormycosis in children and compare them with the present case.

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

Ultrastructural studies of Kaposis 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 μm 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.

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.

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 fetal 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.

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 Dariers 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.

Nephrogenic systemic fibrosis with a spectrum of clinical and histopathological presentation: a disorder of aberrant dermal remodeling

Background: Nephrogenic fibrosing dermopathy (NFD) has emerged as a clinicopathologic entity since 1997 and recently renamed as nephrogenic systemic fibrosis (NSF). The etiology and pathogenesis remain uncertain. Characteristic clinical presentation is described as diffuse thickening and hardening of the skin occurring in patients with renal insufficiency. Typical histological features include proliferation of CD34 positive fibrocytes, increased thick collagen bundles and mucin deposition, without significant inflammatory infiltrate. Variations in clinical presentations have been reported, including papular and plaque‐like skin lesions, focal lesion only, as well as systemic involvement. Histological changes can be subtle and non‐specific, overlapping with other disease processes and harboring features including calcification and osteoclast‐like giant cells with osseous metaplasia.

Specific detection of trichodysplasia spinulosa–associated polyomavirus DNA in skin and renal allograft tissues in a patient with trichodysplasia spinulosa

BACKGROUND Trichodysplasia spinulosa (TS) is a rare, disfiguring skin condition that affects immunosuppressed patients, universally involving the central face. New data point to the recently discovered TS-associated polyomavirus (TSPyV) as the causative agent. OBSERVATIONS We report a case of TS in a 48-year-old African American man after renal transplant; via polymerase chain reaction and sequencing, confirm the detection of TSPyV in lesional skin; and report the novel detection of TSPyV DNA in renal allograft tissue. Results of polymerase chain reaction analysis were negative for Merkel cell polyomavirus in lesional skin. Fifteen months later, urine cytologic findings showed morphologic evidence of a urinary tract polyomavirus infection. Results of SV40 immunohistochemical analysis were negative in lesional skin, renal allograft, and urine specimens. CONCLUSIONS To our knowledge, this is the first reported case in which TSPyV DNA has been detected in extracutaneous tissues and the third with combined ultrastructural and molecular confirmation of the presence of TSPyV in lesional skin. Lack of detection of other pathogenic human polyomaviruses in this patients skin supports the specific role of this polyomavirus in the genesis of TS. Further basic science studies are needed to determine the exact pathomechanisms of this polyomavirus and to explore possible tumorigenic roles in other skin diseases.

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.

Quantitative image analysis of p53 protein accumulation in keratoacanthomas

&NA; 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.