Biomedical subjects
Publications and source records attributed to P L Myskowski.
Carcinoma of the cervix is a common neoplasm, which annually affects 50,000 women in the United States. When cervical carcinoma metastasizes, it most often involves the lung, bone, and liver; only rarely does it metastasize to the skin. We describe a patient with previously diagnosed carcinoma of the cervix who presented with a lesion on the lateral aspect of her left leg.
OBJECTIVE: To evaluate the efficacy and safety of topical alitretinoin gel (9-cis-retinoic acid [LGD1057], Panretin gel; Ligand Pharmaceuticals, Inc, San Diego, Calif) in cutaneous Kaposi sarcoma (KS). DESIGN: Open-label, within-patient, controlled, dose-escalating phase 1 and 2 clinical trials. In all patients, 1 or more cutaneous KS lesions were treated with alitretinoin gel, and at least 2 other lesions served as untreated controls for up to 16 weeks. Alitretinoin (0.05% or 0.1% gel) was applied twice daily for the first 2 weeks and up to 4 times daily thereafter, if tolerated. SETTING: Nine academic clinical centers. PATIENTS: One hundred fifteen patients with biopsy-proven acquired immunodeficiency syndrome (AIDS)-related KS. MAIN OUTCOME MEASURES: AIDS Clinical Trials Group response criteria. RESULTS: Statistically significant clinical responses were observed in 31 (27%) of 115 patients for the group of treated index lesions compared with 13 (11%) for the group of untreated control lesions (P<.001). Responses occurred with low CD4(+) lymphocyte counts (<200 cells/microL) and in some patients with refractory response to previous systemic anti-KS therapy. The incidence of disease progression was significantly lower for treated index lesions compared with untreated control lesions (39/115 [34%] vs 53/115 [46%]; P =.02). Alitretinoin gel generally was well tolerated, with 90% of treatment-related adverse events confined to the application site and only mild or moderate in severity. CONCLUSIONS: Alitretinoin gel has significant antitumor activity as a topical treatment for AIDS-related KS lesions, substantially reduces the incidence of disease progression in treated lesions, and is generally well tolerated.
Mycobacterium haemophilum is an emerging pathogen in immunocompromised patients. We report the clinical and histologic findings of 16 skin biopsies from 11 patients with culture-proven infections by M. haemophilum. The patients had leukemia or non-Hodgkin's lymphoma. Ten of them had undergone bone marrow transplantation. When the skin biopsy specimens were taken, a portion of the skin was simultaneously submitted to a microbiology laboratory for cultures. The remaining skin was processed routinely. Acid-fast bacilli were found in 11 of 16 lesions. The number of histologically detectable organisms was typically low: nine biopsies had fewer than three bacilli per 50 oil immersion fields. The most common histologic pattern was a mixed suppurative and granulomatous reaction (7 of 16 biopsies). Four biopsies showed well-formed epithelioid granulomas. Two showed necrosis, one of which was ulcerated. One lesion was a subcutaneous abscess. Two biopsies showed a mixed lichenoid and granulomatous dermatitis. In one of them, the granulomatous reaction was focal and small. One biopsy lacked a granulomatous tissue reaction altogether; it showed an interface dermatitis, a perivascular and periadnexal lymphocytic infiltrate, and necrotizing lymphocytic small vessel vasculitis. A subsequent biopsy from the same patient additionally showed a focal granulomatous reaction. Our observation that infections by M. haemophilum can present with nongranulomatous or pauci-granulomatous reactions without necrosis is of note. Failure to suspect mycobacterial infection in such reactions contributes to probable underreporting of M. haemophilum and to misdiagnoses. Furthermore, our findings emphasize the importance of simultaneous biopsies for culture and histology in immunocompromised patients.
KS remains a challenge to clinicians and investigators more than a century after its initial description. Debate continues as to the cell of origin, as well as whether or not it is a true cancer. KS appears to be an opportunistic neoplasm, which in its earliest phase retains some features of a benign hyperproliferative process, but in its late stages behaves like an aggressive malignancy. Pathogenesis seems to involve a predisposed individual (genetically susceptible or immunologically compromised) who comes into contact with an infectious agent, most likely a virus. Cytokines appear to play a major role in the growth of the tumor. The exact role of the KSHV in this process will likely be the subject of much investigation in the future.
A variety of superficial and deep mycoses may affect the immunocompromised patient. Among the superficial mycoses, candidal infections are common in all groups, but dermatophyte and pityrosporum infections may also be found. Although not primarily dangerous, they may lead to secondary bacterial infections and morbidity. Of the systemic mycoses, candidiasis, aspergillosis, and mucor-mycosis are frequently lethal and require early diagnosis and aggressive antifungal treatment. Endemic mycoses, such as histoplasmosis and coccidioidomycosis, may result in severe and often fatal infections in those patients with cellular immune alterations. The identification and prophylaxis of high-risk patients and the development of more effective antifungal therapies are beginning to have an impact on the control of fungal disease in this population.
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Cutaneous disorders occur with great frequency in patients with HIV infection and increase in number and severity as the disease progresses and immune function declines. In addition, the first findings related to HIV infection are often on the skin. Cutaneous infections with herpesviruses may be severe and atypical in their presentations; papillomaviruses and MC are common as well. Bacterial infections may be primary or secondary to other skin diseases; superficial and deep fungal infections are also prevalent. Papulosquamous disorders, including seborrheic dermatitis, psoriasis, and eczema, may be disfiguring and result in secondary complications. Neoplastic disorders, especially Kaposi's sarcoma, demand early diagnosis, to afford the patient maximal treatment options. All physicians must be aware of these cutaneous manifestations to decrease morbidity and improve quality of life in the HIV-infected individual.
PURPOSE: Cellulitis is a previously unreported complication of conservative surgery and radiation therapy for early stage breast cancer. Patients who presented with breast cellulitis after conservative therapy are described. METHODS AND MATERIALS: Eleven patients that developed cellulitis of the breast over a 38-month period of observation are the subject of this report. Clinical characteristics of patients with cellulitis and their treatment and outcome are reported. Potential patient and treatment-related correlates for the development of cellulitis are analyzed. RESULTS: The risk of cellulitis persists years after initial breast cancer therapy. The clinical course of our patients was variable: some patients required aggressive, long-duration antibiotic therapy, while others had rapid resolution with antibiotics. Three patients suffered from multiple episodes of cellulitis. CONCLUSION: Patients with breast cancer treated with conservative surgery and radiotherapy are at risk for breast cellulitis. Systematic characterization of cases of cellulitis may provide insight into diagnosis, prevention, and more effective therapy for this uncommon complication.
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The relationship between 22 histologic variables and survival was investigated in 93 patients with acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). All the patients were homosexual men in whom KS was the initial manifestation of AIDS. All patients were followed for at least 12 months or until death. Histologic specimens of the initial KS biopsy were reviewed in a blind manner by two of the authors and were evaluated for the presence of a number of histologic features. In a univariate analysis nodular lesions of KS (upsilon patch or plaque lesions), the absence of hemosiderin, the absence of irregular vascular spaces, and the presence of spindle cell nodules were all significantly associated with increased length of survival. Two variables previously shown to be related to survival (CD4:CD8 cell ratio, initial lesion on lower extremities) were included in a multivariate analysis (Cox model) in addition to the histologic variables. Complete data were available from 85 patients. In the multivariate analysis a higher helper to suppressor T-cell ratio, initial lesion on lower extremities, presence of spindle cell nodules, and nodular histology (upsilon patch or plaque histology) were all significantly associated with increased length of survival. These data suggest that in AIDS-associated KS, as in reticuloendothelial neoplasms, histologic features may be useful in identifying prognostically different subgroups of patients.
BACKGROUND: Molluscum contagiosum (MC) is a common and at times severely disfiguring cutaneous viral infection in patients with human immunodeficiency virus (HIV) infection. OBJECTIVE: The purpose of this study was to describe the clinical course of MC in patients with HIV infection and to examine the relation between presentation of MC and the stage of HIV infection, as measured by T-cell subsets. METHODS: This is a retrospective case study of 27 patients with MC and HIV infection who had T-cell subset determination within 60 days of diagnosis of MC. RESULTS: The overall mean CD4+ count, CD4+ percentage, and CD4+/CD8+ ratio were 85.7/mm3, 5.9%, and 0.10, respectively. An inverse relation between CD4+ count and the number of MC lesions was observed (p = 0.0023). Fourteen patients (52%) had facial and neck lesions alone, and seven (26%) had lesions in areas associated with sexual transmission. Pneumocystis carinii pneumonia had occurred in 8 patients (31%) and Kaposi's sarcoma in 15 patients (56%). CONCLUSION: MC can occur as a late manifestation of HIV infection and is a cutaneous correlate of cellular immune deficiency.
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Kaposi's sarcoma (KS) presents with variable severity in the context of HIV infection. Various therapeutic approaches can be taken, and these are determined by the extent and location of KS lesions and the severity of tumor-related symptoms. New insights into the pathogenesis of KS lesions may provide innovative treatment strategies and a more rational basis for the control of this neoplasm.
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During cryosurgery of different types of lesions in patients with human immunodeficiency virus infection, it is crucial that the possibility of secondary bacterial infection be reduced. The use of disposable attachments during cryosurgery can reduce this risk of transmission of infectious agents. These attachments are discussed.