Severe distributive shock, neutrophilic dermatosis, and ST-elevation myocardial infarction in the setting of azathioprine hypersensitivity syndrome.

BACKGROUND: Azathioprine is a purine synthesis inhibitor used as an immunosuppressive therapy for many immune-mediated diseases. Azathioprine hypersensitivity reaction is a rare, life-threatening adverse reaction characterized by a range of multisystem manifestations including fever, abdominal pain, arthralgias, erythematous cutaneous eruption, acute renal failure, neutrophilia, and more rarely, distributive shock. Although acute heart failure has been rarely described in association with azathioprine hypersensitivity syndrome, myocardial infarction has, to our knowledge, never been associated with this entity. CASE PRESENTATION: We describe a case of a 59-year-old male with Crohn's disease who developed severe azathioprine hypersensitivity syndrome that included distributive shock, neutrophilic dermatosis, and acute coronary syndrome with ST-elevation. Clinical improvement was seen after cessation of azathioprine and administration of glucocorticoid therapy. CONCLUSION: Prompt recognition of azathioprine hypersensitivity syndrome, which can manifest as shock and neutrophilic dermatosis, is key to ensure rapid azathioprine cessation.

Blastomycosis presenting as multiple splenic abscesses: Case report and review of the literature.

A 31-year-old Canadian Aboriginal man from northwestern Ontario presented with left upper quadrant pain and a tender left upper quadrant mass. Evaluation with a computed tomography scan showed multiple lesions within the spleen, a collection between the splenic tip and splenic flexure of the colon, and several small adrenal lesions. Computed tomographic-guided needle biopsy showed necrotizing granulomatous inflammation and multinucleated giant cells. Gomori's methenamine silver stain showed broad-based budding yeast consistent with Blastomyces dermatitidis. Abdominal symptoms resolved after two months of oral itraconazole. Multiple splenic abscesses are a rare presentation of blastomycosis and should be considered in the differential diagnosis of left upper quadrant abdominal pain in a patient with a history of travel or residence in a region endemic for B dermatitidis.

Eruptive keratoacanthoma-type squamous cell carcinomas in patients taking sorafenib for the treatment of solid tumors.

BACKGROUND: Protein kinases (PKs) are indispensable for most cellular processes, and deregulation of PKs can lead to activation of oncogenic and anti-apoptotic pathways and immune dysregulation. OBJECTIVE: To report the development of keratoacanthoma (KA)-type squamous cell carcinomas (SCCs) in patients treated with the multikinase inhibitor sorafenib for the treatment of solid tumors, to present the possible mechanisms for induction of these SCCs, and to discuss the implications for discontinuation of therapy and possible cotherapies to decrease this side effect. PARTICIPANTS: Fifteen patients taking the multikinase inhibitor sorafenib for the treatment of solid tumors who developed multiple KA-type SCCs, which continued to develop while the patients were undergoing therapy but stopped with discontinuation of sorafenib. LIMITATIONS: This report is limited because it is a retrospective study that included only patients who developed multiple KA-type SCCs. CONCLUSIONS: Development of cutaneous SCCs appears to be a side effect limited to sorafenib, a multikinase inhibitor that inhibits not only multiple tyrosine kinases (TKs), but also the serine-threonine kinase Raf. The incidence of cutaneous SCCs does not appear greater with multikinase inhibitors that inhibit only TKs.

Does imiquimod histologically rejuvenate ultraviolet radiation-damaged skin?

BACKGROUND: Imiquimod (IMI) 5% is believed by some to result in an improved cosmetic appearance of chronically ultraviolet radiation (UV)-damaged skin. OBJECTIVE: The objective was to determine what histologic and immunohistologic changes were present in actinically damaged skin after treatment with IMI. METHODS AND MATERIALS: Pre- and posttherapy biopsies of 12 patients with histories of actinic keratoses were evaluated with routine histology and immunohistochemical stains including p53, p63, proliferating cell nuclear antigen (PCNA), c-kit, and Factor XIIIa. RESULTS: After IMI therapy there was less compact hyperkeratosis, a more uniform rete ridge pattern with a more ordered proliferation of the epidermis, and a decrease in sun-damaged melanocytes. The papillary dermis showed a more uniform cellularity, and there was increased cellularity within the area of solar elastosis. After therapy, staining for p53, p63, and PCNA was decreased within the epidermis; staining for c-kit was decreased but more uniform in the basal cell; and Factor XIIIa expression was increased within the papillary dermis with a more ordered pattern of staining. CONCLUSION: These morphologic and immunohistochemical patterns may explain some of the improvement in overall skin appearance after IMI therapy and may be related to the spectrum of signaling pathways induced by the imidazoquinolines.

Unusual thromboses associated with protein S deficiency in patients with acquired immunodeficiency syndrome: case reports and review of the literature.

Recent reports indicate that patients infected with HIV are at increased risk for the development of thrombosis. Among other possibilities, an acquired deficiency of protein S (PS), one of the plasma's natural anticoagulants, might explain this tendency. PS deficiency can be classified in three types depending on the levels of total and free protein (antigenic assays) as well as anticoagulant activity (functional assay). Although the prevalence of inherited PS deficiency is not known because of its rarity, several conditions can lead to acquired forms of the disease. We report two AIDS patients with coexistent type III PS deficiency and thrombosis. Our first patient presented with bilateral chronic leg ulcers and a skin biopsy revealed dermal microthromboses. On laboratory evaluation he had PS deficiency and was started on anticoagulation, but was lost to follow-up. The second patient presented with hepatic vein thrombosis (Budd-Chiari syndrome) and was also PS deficient. On long-term anticoagulation, she experienced resolution of the thrombosis. Neither patient had prior personal or family history of venous thrombosis, nor acquired risk factors such as immobility, acute infection, recent surgery, or hormonal therapy. The literature contains a few reports of skin ulcers and Budd-Chiari syndrome associated with PS deficiency, although none in AIDS patients. While a larger number of studies describe an association between PS deficiency and HIV infection, the causal effect of this deficiency on the thrombophilic tendency in AIDS has not been established. We propose that awareness of the increased risk for thrombosis in HIV infection is important to the understanding of disease pathophysiology and management of these patients.

Unexplained hypereosinophilia and the need for cytogenetic and molecular genetic analyses.

BACKGROUND: Idiopathic hypereosinophilic syndrome (HES) is a diagnosis made after the exclusion of other causes of eosinophilia. However, differentiation of idiopathic HES from eosinophilic leukemia is sometimes difficult. In some cases, these diagnoses can be differentiated by cytogenetic or molecular findings, as illustrated in the patients described herein. OBSERVATIONS: We describe 3 patients with HES and associated pruritus; 1 patient also had recurrent lesions of eosinophilic cellulitis. All 3 patients were initially diagnosed as having idiopathic HES, but after evaluation and demonstration of molecular abnormalities, they were classified as having eosinophilic leukemia. CONCLUSIONS: Patients with a diagnosis of idiopathic HES should be evaluated for cytogenetic or molecular genetic abnormalities. These abnormalities can establish a diagnosis of chronic eosinophilic leukemia and may provide clues for emerging therapies.

Digital image acquisition using a consumer-type digital camera in the anatomic pathology setting.

Imaging is central to anatomic pathology. The captured images are used for documentation, archiving, teaching, and publication. The advent of low-cost, consumer-type, high-end digital cameras has provided a convenient, easy-to-use alternative for routine image acquisition. The various applications for digital image acquisition in anatomic pathology include, among others, digitizing conventional photographs, digital gross photography and digital macrophotography, digitizing radiographic images, and digital photomicrography. This article reviews digital image acquisition in the anatomic pathology setting using a consumer-type digital camera. The camera type chosen as an example for the discussion was selected for its popularity and wide use among pathologists and for its potential to function as a sole image input device in all applications combined. Techniques and accessories to further increase the functionality of the camera and help overcome some of the commonly encountered problems in some applications are described.

Histologic features in primary cutaneous squamous cell carcinomas in immunocompromised patients focusing on organ transplant patients.

BACKGROUND: In organ transplant recipients (OTR) there is an increased incidence of cutaneous squamous cell carcinomas (CSCC), and they may be aggressive. OBJECTIVE: We wanted to determine whether any histologic features were characteristic or more common in CSCC of OTR. METHODS: A total of 518 immunocompetent individuals with 601 primary CSCC were examined. Seventy-nine OTR with 231 primary CSCC, 53 renal OTR, 25 heart/heart lung OTR, and 1 liver OTR were examined. RESULTS: In all patient populations, CSCC occurred dominantly in chronically sun-exposed skin. In OTR, however, a greater percentage occurred on the extremity, particularly the upper extremity, and they occurred at an earlier age. Features that were significantly more common in OTR were acantholytic changes, early dermal invasion, an infiltrative growth pattern with or without desmoplasia, and Bowen's disease with carcinoma. In OTR primary CSCC were also significantly deeper at time of diagnosis. CONCLUSIONS: Our findings confirmed the association of ultraviolet radiation exposure with development of CSCC in OTR. The increased depth of the primary CSCC in OTR is surprising because these patients are followed closely for skin cancer compared with immunocompetent patients. The other morphologic features that were significantly more common in OTR may theoretically reflect not only the type of iatrogenic immunosuppression in these patients, but also other procarcinogenic effects of their medications.

Topical application of dimethylbenz[a]anthracene results in the generation of multiple melanocytic nevi in C3H/HeN mice.

Melanocytic nevi are a common dermatological problem for which there are few in vivo models. It has been postulated that environmental factors contribute to their development. Experiments were therefore conducted to determine whether application of dimethylbenz[a]anthracene (DMBA) to the skin of mice would result in the development of melanocytic nevi. One hundred microliters of a 0.1%, 0.5%, or 1.0% solution of DMBA was applied to the dorsal skin of C3H/HeN mice. The mice were then observed for the appearance of pigmented lesions. Histological examination revealed perifollicular accumulations of nevus cells, which were S-100-protein and HMB-45-positive, confirming their melanocytic origin. Pigmented lesions did not occur in animals treated with vehicle alone. Dose response studies revealed both greater numbers of nevi and lesions with larger diameters as the dose of DMBA was increased from 0.1% to 0.5%. In no instance was an invasive melanoma observed even after 40 weeks. The fact that melanocytic nevi can be produced by topical application of DMBA suggests that xenobiotics may play a previously unrecognized role in the development of this common benign neoplasm. Because this is one of the only animal models for melanocytic nevi, further examination of this model may facilitate identification of the molecular and biochemical mechanisms that lead to the development of pigmented nevi and the factors that promote their evolution into invasive melanomas.

Giant basal cell carcinoma associated with human papillomaviruses infection.

Different criteria have been used to define giant basal cell carcinoma (BCC). However, the majority of tumors of 10 cm or greater in diameter have a characteristic clinical and histopathologic presentation. As a group, these tumors often show metastatic spread as opposed to all other BCCs that rarely metastasize. We present an additional patient with a giant BCC greater than 100 cm2. This tumor had a characteristic location and infiltrative growth pattern. Unusual features of this tumor included a lack of expression of BCL-2 with a greater proportion of cycling tumor cells expressing proliferation markers than conventional BCC, as well as expression of anogenital human papillomaviruses (HPV) subtypes with oncogenic potential. The association of HPV with BCCs has rarely been studied and may not be identical to HPV-induced genital squamous cell carcinomas. However, the findings in this patient suggest that HPV may play a role in the development of some chronic giant BCCs.