Heparin-induced haemorrhagic bullous dermatosis.

BACKGROUND: Heparin-induced haemorrhagic bullous dermatosis (HBD) is a rare but probably underdiagnosed reaction to heparin, with 26 cases reported in the English literature. Currently, there is no consensus regarding the treatment. AIM: To assess our new cases of HBD and review the previously reported cases, in order to draw conclusions about this adverse skin reaction to heparin. METHODS: A PubMed search was performed for articles containing the terms '(heparin-induced AND (blister OR bulla OR bullae)) OR (hemorrhagic bullous dermatosis AND heparin) OR heparin bullous dermatosis'. Descriptive statistical data analysis was performed using Microsoft Excel. RESULTS: We assessed five new cases of HBD. In addition, our literature search revealed 26 previously reported patients. Combining these, we found that the mean ± SD age of patients with HBD was 71.4 ± 14 years. HBD affects men more commonly than women (men 22/31; P = 0.02). Patients develop tense bullae most frequently on the extremities, approximately 8 days (mean ± SD 7.5 ± 6.4 days) after starting treatment with a heparin product, usually enoxaparin. CONCLUSIONS: The typical clinical course is spontaneous resolution within days to weeks irrespective of continuation of heparin therapy. Because of its self-limiting nature, interruption of heparin therapy may not be required.

Benign cylindroma causing transcalvarial invasion in a patient with familial cylindromatosis.

OBJECTIVE: To describe a case of scalp cylindroma without features of malignancy invading through the skull and dura, and producing massive intracranial extension. Tumors of epidermis and epidermal appendages rarely show bony invasion, but invasive tendency in some tumor types has been associated with increased TP53 expression. PATIENT AND METHODS: Patient with familial cyindromatosis (Brooke-Spiegler syndrome) who had undergone numerous previous surgical excisions over the past 30 years of his scalp cylindromas. Light microscopic and immunohistochemical characterization of resected tumor, with TP53 immunostaining in the invasive tumor was compared with that seen in five other cutaneous, non-invasive cylindromas. RESULTS: Tumor showed no increase in mitotic rate or increased immunostaining for TP53. CONCLUSION: Multiple previous surgeries down to pericranium may have contributed to local weakening of tissues and facilitated transcalvarial invasion. While an uncommon occurrence, both benign and malignant cylindromas have the capacity to invade bone, particularly in patients with the familial syndrome.

The specialty of the treating physician affects the likelihood of tumor-free resection margins for basal cell carcinoma: results from a multi-institutional retrospective study.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cutaneous malignancy. Surgical experience and physician specialty may affect the outcome quality of surgical excision of BCC. METHODS: We performed a multicenter retrospective study of BCC excisions submitted to the respective Departments of Pathology at 4 major university medical centers. Our outcome measure was presence of histologic evidence of tumor present in surgical margins of excision specimens (incomplete excision). Clinician experience was defined as the number of excisions that a clinician performed during the study interval. The analytic sample pool included 1459 tumors that met all inclusion and exclusion criteria. Analyses included univariate and multivariate techniques involving the entire sample and separate subsample analyses that excluded 2 outlying dermatologists. RESULTS: Tumor was present at the surgical margins in 243 (16.6%) of 1459 specimens. A patient's sex, age, and tumor size were not significantly related to the presence of tumor in the surgical margin. Physician experience did not demonstrate a significant difference either in the entire sample (P <.09) or in the subsample analysis (P >.30). Tumors of the head and neck were more likely to be incompletely excised than truncal tumors in all the analyses (P <.03). Compared with dermatologists, otolaryngologists (P <.02) and plastic surgeons (P <.008) were more likely to incompletely excise tumors; however, subsample analysis for plastic surgeons found only a trend toward significance (P <.10). Dermatologists and general surgeons did not differ in the likelihood of performing an incomplete excision (P >.4). CONCLUSION: The physician specialty may affect the quality of care in the surgical management of BCC.

Pediatric melanoma: are recent advances in the management of adult melanoma relevant to the pediatric population.

PURPOSE: Although melanoma in childhood is a rare condition, there is evidence that it is increasing in frequency. As advances are being made in the understanding and therapy of adult melanoma, we need to consider the relevance of these advances to the pediatric population. PATIENTS AND METHODS: We have reviewed our experience at the University of Colorado Health Sciences Center with the clinical parameters, therapy, and outcomes of melanoma in 27 patients age 16 years or younger and contrasted these to the adult experience. RESULTS: Most cases were diagnosed early with the median thickness of the primary melanoma being 0.75 mm. Six of seven patients who had lymph node metastases develop remain alive at a median follow-up of 62 months. Durable complete responses to a variety of therapies were seen in three of five patients with advanced disease outside the central nervous system. Our experience with sentinel node biopsy, adjuvant interferon, and new therapies for metastatic melanoma were also reviewed and appear to be relevant for younger patients. CONCLUSIONS: The behavior of melanoma in the pediatric population at our center is similar to that seen in adults. The integration of recent advances in the staging and therapy of melanoma in adults would be of benefit to children with this condition.

Primary noncutaneous melanoma.

Primary noncutaneous melanomas are rare neoplasms that affect patients in an older age group than primary cutaneous melanomas. The prognosis is worse than primary cutaneous melanomas because of the advanced stage at the time of diagnosis, the rich vascular and lymphatic supply of mucosal sites, and the lack of clinical suspicion of the tumor because of its rarity. The initial treatment is surgical resection but the location may make it technically difficult to obtain complete tumor removal. Unlike cutaneous melanoma, sun exposure is not a risk factor for noncutaneous melanomas. Darker-skinned individuals may have a higher incidence of some noncutaneous melanomas, such as anorectal melanomas. It is important for clinicians and pathologists to recognize primary noncutaneous melanomas to provide early detection and optimum management.

Sialadenoma papilliferum of the palate: case report and literature review.

Sialadenoma papilliferum (SP) is a rare tumor of salivary gland ducts which bears a strong histologic resemblance to the more common syringocystadenoma papilliferum (SCAP). We report a case occurring on the palate of a 50-year-old man, and review the clinical and histologic features of this tumor. Because of the histologic similarities between these two tumors and squamous papillomas, polymerase chain reaction (PCR) for human papilloma virus (HPV) DNA was performed on this tumor and on two cases of SCAP, with negative results. To our knowledge, this is the first case report of SP in the dermatopathology literature.

Comparison of in vivo and in vitro measures of beryllium sensitization.

Chronic beryllium disease (CBD) diagnosis hinges on demonstrating a cell-mediated immune response to beryllium salts in vitro with the beryllium lymphocyte proliferation test (BeLPT). The BeLPT has found widespread application in screening for CBD and beryllium sensitization in populations of exposed workers. We hypothesized that the in vivo beryllium salt patch test may be of value as an adjunct to the BeLPT, rectifying false negative or ambiguous blood test results. We studied subjects with CBD (n = 11), beryllium sensitization without disease (n = 3), and control subjects with dermatitis (n = 20). Evaluation included completion of a demographic questionnaire, blood BeLPT (if CBD or beryllium-sensitized), and beryllium patch testing with 0.1% and 1% beryllium sulfate (BeSO4) in petrolatum and in aqueous vehicles. Biopsies were performed at abnormal patch test sites in five subjects. The 1% aqueous BeSO4 proved superior either to 1% petrolatum or 0.1% solutions, producing positive reactions in all CBD and beryllium-sensitized subjects. We observed no long-term adverse reactions. Biopsies demonstrated spongiotic changes early, followed by noncaseating granulomas within 18 days. We conclude that the beryllium patch test can be used safely to clarify the sensitization state and diagnosis of CBD.

Hypermelanotic nevus: clinical, histopathologic, and ultrastructural features in 316 cases.

We report on a series of benign melanocytic nevi that have unique clinical, histopathologic, and ultrastructural features. Between March 1993 and February 1994, 316 examples of hypermelanotic nevi were received by the dermatopathology laboratory at Denver General Hospital. Our study identified the clinical characteristics, histopathologic criteria, and ultrastructure of this lesion. Clinically, the lesions were dark brown to black macules or papules. The most common location was the back. There was a slight female predominance, and the mean age of our patients was 40 years. Histopathologically, the nevus showed the following characteristics: (a) melanin within a compact stratum corneum, (b) small nests of nevus cells at the dermal-epidermal junction and (in 52% of the cases), nests within the papillary dermis, (c) heavy melanin within keratinocytes in the lower epidermis, (d) a sparse to moderate lymphocytic infiltrate and melanophages in the superficial dermis, and (e) an absence of cytologic atypia. Electron microscopy revealed that abundant melanin was packaged in melanosome complexes within keratinocytes. Less pigmented melanocytes and nevus cells contained well-developed dendritic processes and golgi, indicative of efficient melanin transfer. According to our retrospective case control analysis, patients with hypermelanotic nevi were older and more likely to be male than those with ordinary nevi. Hypermelanotic nevi were more likely than controls to be junctional nevi; they were smaller, dark brown or black in color, and clinically suspicious for melanoma. We propose the name "hypermelanotic nevus" to describe this benign lesion, which is often biopsied to exclude melanoma.

Detection of human papillomavirus DNA in squamous cell carcinomas of a patient with mycosis fungoides: report of a case.

Human papillomaviruses (HPV) have been associated with squamous cell carcinomas (SCC) of the skin in both the immunocompetent and the immunocompromised individual. A paucity of literature, however, exists concerning the presence of HPV in SCCs from patients with mycosis fungoides (MF)-[cutaneous T-cell lymphoma (CTCL.)]. We describe a case of multiple SCCs in which HPV DNA was detected over a 9-year period from a patient with MF. This patient with a long history of MF developed 7 small red scaly indurated lesions of sun and non-sun-exposed areas during a 9-year period (1981-1989). Histologic examination of all the lesions revealed that they were SCCs. The patient had no recorded history of arsenic exposure. To investigate the possible role of HPV as a co-carcinogen, we tested the 7 cases of SCC for HPV. Polymerase chain reaction (PCR) was performed on formalin-fixed tissue sections using HPV L.1 consensus sequence primers. Four of the 7 SCCs were positive for HPV DNA. These results suggest a possible role for HPV as a co-carcinogen in the development of SCCs in this patient.

Eosinophilic and neutrophilic spongiosis: clues to the diagnosis of immunobullous diseases and other inflammatory disorders.

When eosinophils or neutrophils are found within the epidermis in concert with edema, the pattern is known as eosinophilic or neutrophilic spongiosis. Although eosinophilic spongiosis has been accepted as a clue to the diagnosis of blistering disorders for some time, the fact that either pattern can serve as a clue to the diagnosis of a variety of disorders, including immunobullous diseases, is less widely known. Herein, we review the types of inflammatory skin diseases, including spongiotic dermatitides, subepidermal vesicular dermatitides, intraepidermal vesicular dermatitides, and perivascular or diffuse dermatitides, that display intraepidermal eosinophils and neutrophils. We also review the known mechanisms that explain in part why intraepidermal granulocytes are commonly found in this diverse group of skin diseases.

Sweat gland carcinoma in a human immunodeficiency virus-infected patient.

Eccrine (sweat gland) carcinoma is a rare form of skin cancer that may be locally destructive. It is known to recur after resection and can metastasize to regional or distant lymph nodes. There have been two reported cases in association with patients immunocompromised as the result of organ transplantation (I. Penn: Prog Allergy. 37: 259, 1986). We report here the first case of sweat gland carcinoma in a patient infected with the human immunodeficiency virus.

Systemic therapy of cutaneous T-cell lymphomas (mycosis fungoides and the Sézary syndrome).

OBJECTIVE: To review recent studies of systemic therapy for mycosis fungoides and the Sézary syndrome (cutaneous T-cell lymphomas). DATA SOURCES: English-language articles indexed in MEDLINE from 1988 through 1994. STUDY SELECTION: All therapeutic studies were selected. DATA EXTRACTION: The data were abstracted without judgments on response criteria or patient numbers. Data quality and validity were assessed by independent author reviews. DATA SYNTHESIS: No systemic therapy cures patients with cutaneous T-cell lymphomas. Single and combined chemotherapeutic agents produce high response rates. Whether any of these is preferred is not established. A randomized trial comparing combination chemotherapy plus radiation therapy with topical therapy showed no survival benefit for the combination. Several adenosine analogs and retinoids were active, but their optimal use is uncertain. Interferons are as active as chemotherapeutic agents and may be less toxic. Interferon combined with psoralen plus ultraviolet A light therapy produces high complete response rates and long-lasting remissions. Combinations with other systemic therapies do not increase response rates. Photopheresis therapy should be regarded as experimental. Promising preliminary results were seen with interleukin-2 fusion toxins and several antibody conjugates. CONCLUSIONS: Systemic therapy should be considered effective and palliative. The principles of treating all low-grade lymphomas can be applied. Randomized trials are needed to evaluate new agents (such as a comparison of psoralen plus ultraviolet light with or without interferon), and large phase II trials are needed for new agents such as photopheresis, interleukin-2 fusion toxin, temozolomide, and others.

Melanocytic nevi with focal atypical epithelioid cell components: a review of seventy-three cases.

BACKGROUND: We report a variant of melanocytic nevus that may be confused with melanoma. OBJECTIVE: The purpose of this study is to describe the clinical, histologic, and biologic features of nevi with focal atypical epithelioid cell components (clonal nevi). METHODS: Seventy-three cases were retrieved by reviewing lesions previously diagnosed as clonal, combined, deep penetrating, and inverted type-A nevi. Histologic features were assessed and referring physicians received a questionnaire about the presentation and outcome of each case. RESULTS: Histologically, all cases had a biphasic pattern characterized by an ordinary nevus that contained a darkly pigmented collection of large distinct epithelioid melanocytes in the superficial dermis. Immunostains identified mutant p53 proteins in 50% of dermal clones (9 of 18) but not in ordinary nevus cells adjacent to the clones. We are not aware of any patient developing a malignant melanoma (mean follow-up 24.5 months), including 41 cases that were initially incompletely excised. CONCLUSION: Clonal nevi are a distinct variant of melanocytic nevi and should be distinguished from malignant melanoma arising in a preexisting nevus.

Ras mutations in human melanoma: a marker of malignant progression.

In this study we address whether there is an association between ras mutations and disease progression in malignant melanoma. DNA was extracted from 100 paraffin-embedded melanomas and sequences around the 12th, 13th and 61st codons of N-, H-, and K-ras were amplified using the polymerase chain reaction and probed for single base pair mutations using synthetic oligonucleotide probes. Thirty-six melanomas contained mutations, which in 25 cases (69%) occurred at the 61st codon of N-ras. The results from dot blot hybridizations were confirmed by subcloning and sequencing the polymerase chain reaction products from two tumors. No ras mutations were found in Clark's level I melanomas, whereas 19% of level II and 45% of the more advanced primary tumors contained ras mutations (Chi squared test: p < 0.05). The median Breslow thickness of primary melanomas with ras mutations was 0.72 mm, significantly thicker than the 0.42 mm of melanomas without mutations (Mann-Whitney U test, p = 0.042). Ras mutations were found more frequently in primary tumors from continuously exposed skin (56%) than tumors from intermittently or non-sun exposed sites (21%). Fifty percent of locally recurrent and 47% of metastatic melanomas had ras mutations. We conclude that ras mutations occur in a subset of melanomas from sun-exposed skin as a feature of tumor progression.

Examination of cutaneous T-cell lymphoma for human herpesviruses by using the polymerase chain reaction.

The etiology of cutaneous T-cell lymphoma remains unknown, although an association with viral infection, in particular certain retroviruses and human herpesviruses, has been suggested. The purpose of this study was to examine skin biopsies of cutaneous T-cell lymphoma for the presence of Epstein-Barr virus, herpes simplex virus type 1 and type 2, and human herpesvirus-6 by using the polymerase chain reaction. Lesional skin biopsies from 30 patients with cutaneous T-cell lymphoma were studied. Control specimens included biopsies from 9 patients with lymphomatoid papulosis and 10 patients with pityriasis lichenoides et varioliformis acuta. DNA extracted from each specimen, as well as from a known positive control for each virus, was examined by using the polymerase chain reaction with viral-specific primers. Each DNA specimen was also amplified with control primers for human beta globin. The specificity of the amplified products was confirmed by Southern analysis. Neither Epstein-Barr virus nor herpes simplex virus was detected in any of the patient specimens examined. Human herpesvirus-6 was detected in one specimen of cutaneous T-cell lymphoma and one specimen of lymphomatoid papulosis. These results do not support a role for any of these herpesviruses in the pathogenesis of cutaneous T-cell lymphoma.