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.

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.

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.

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.

Clinical, histologic, and immunofluorescent distinctions between subacute cutaneous lupus erythematosus and discoid lupus erythematosus.

Subacute cutaneous lupus erythematosus (SCLE) was originally described and distinguished from discoid lupus erythematosus (DLE) on the basis of clinical examination of the skin, but subsequent reports have questioned the concept of SCLE as a marker of a unique subset of LE patients. We classified 27 lupus patients, on the basis of cutaneous exam, as having discoid lupus skin lesions, subacute cutaneous skin lesions, or systemic lupus erythematosus (SLE) without DLE or SCLE lesions. Clinical features most characteristic of SCLE rather than DLE were superficial, non-indurated, non-scarring lesions, and photosensitivity, with lack of induration being the single most helpful finding. Histologic examination of lesional skin showed a relatively sparse, superficial infiltrate in SCLE and a denser, deeper infiltrate in DLE. A distinctive pattern of staining with direct immunofluorescence, particulate epidermal IgG deposition, was found in seven of seven SCLE patients (all anti-Ro/SSA positive) and none of the other patients. This distinctive pattern can be reproduced experimentally when anti-Ro/SSA autoantibodies are infused into human skin-grafted mice. Particulate dermal-epidermal junctional staining was the pattern seen in the patients who did not have SCLE. Clinically defining SCLE as a superficial inflammatory form of cutaneous lupus (i.e., considering lesions to be DLE if they are indurated) results in a meaningful segregation of SCLE and DLE patient groups. The epidermal IgG deposits unique to SCLE provide independent evidence that the clinical findings that were used to identify the patient groups actually identify distinctive cutaneous lupus subsets. The observation that antibodies are present in a different location in the skin in SCLE than in DLE indicates that SCLE and DLE are likely to have different pathomechanisms.

Papulonodular dermal mucinosis in lupus erythematosus.

We report two cases of lupus erythematosus (LE) in which a truncal papulonodular eruption predominated. Histologically the lesions were characterized by diffuse dermal mucin without the usual inflammatory or epidermal changes of LE. It is uncommon in LE for dermal mucin to be present in a sufficient quantity to produce a papulonodular eruption in the absence of typical epidermal changes.

L-tryptophan syndrome: histologic features of scleroderma-like skin changes.

The eosinophilia-myalgia syndrome (EMS) associated with the ingestion of L-tryptophan (LT) containing products has recently been recognized in the United States. We report the histologic features of the cutaneous scleroderma-like changes in four patients. All of the patients met the Center for Disease Control criteria for EMS and had a history of LT ingestion. Skin biopsies showed increased dermal mucin and dermal sclerosis, with trapping of adnexal structures. There are clinical and histologic similarities between EMS, scleroderma, the toxic oil syndrome, and fasciitis with eosinophils.

Cutaneous macroglobulinosis. A case report with unique ultrastructural findings.

BACKGROUND: Cutaneous macroglobulinosis is a rare cutaneous manifestation of Waldenström's macroglobulinemia. Lesions result from the direct deposition of macroglobulin in the skin and have been called IgM storage papules. A case of cutaneous macroglobulinosis with unique ultrastructural findings was studied. OBSERVATIONS: Cutaneous macroglobulinosis is characterized by multiple flesh-colored papules on extensor skin surfaces. Histologically, there are dermal collections of eosinophilic hyaline material, simulating amyloid. The material is positive on periodic acid-Schiff staining. Amyloid stains are negative or equivocal. Electron microscopy reveals thick, nonbranching, 56-nm-wide, linear material with cross striations at 12-nm intervals. These ultrastructural findings differ from the three previously reported cases. CONCLUSIONS: Cutaneous macroglobulinosis may be a rare presenting sign of Waldenström's macroglobulinemia. Deposits of macroglobulin in the skin result in a histologic picture that greatly resembles amyloid. Histochemical stains, direct immunofluorescence microscopy, and electron microscopy are useful tools that enable accurate diagnosis and help to distinguish cutaneous macroglobulinosis from other deposition disorders.

Rheumatoid neutrophilic dermatitis.

Rheumatoid neutrophilic dermatitis is a rare entity reported to occur in association with severe rheumatoid arthritis. Three patients with seropositive rheumatoid arthritis and rheumatoid neutrophilic dermatitis are described. Clinically, the eruption is characterized by symmetric erythematous papules, plaques, and rarely vesicles on extensor skin surfaces. Light microscopy reveals a dermal neutrophilic infiltrate without vasculitis. Spongiotic intraepidermal blisters, subepidermal bullae, or papillary neutrophilic microabscesses may be seen. The histologic differential diagnosis includes the other dermatoses in which neutrophils predominate. Rheumatoid neutrophilic dermatitis is one of several neutrophilic dermatoses seen in association with rheumatoid arthritis, suggesting that it may be part of a spectrum of neutrophilic cutaneous reaction patterns in a predisposed host.