Klaus F. Helm

Cutaneous metastases in patients with metastatic carcinoma: A retrospective study of 4020 patients

BACKGROUND Most previous studies have found that cutaneous metastases occur infrequently and are rarely present at the time the cancer is initially diagnosed. OBJECTIVE We studied patients with metastatic cancer to determine the overall frequency of skin metastases, the frequency that these were the first sign of extranodal disease, and the clinical and histologic features of the cutaneous lesions. METHODS A 10-year period of tumor registry files was searched for patients with metastatic carcinoma and melanoma. For patients with skin metastases, medical records and pathology reports were also examined. RESULTS Of 4020 patients with metastatic disease, 420 (10%) had cutaneous metastases; in 306 of them the skin metastases were the first sign of extranodal metastatic Breast cancer and melanoma were the most common. Nodules were the most frequent clinical presentation, although inflammatory, cicatricial, and bullous lesions were also noted. Incisional metastases were common. Histologic findings most frequently revealed adenocarcinoma that was sometimes suggestive of the site of origin. After recognition of skin metastases, mean patient survival ranged from 1 to 34 months depending on tumor type. CONCLUSION Cutaneous metastases are not uncommon and frequently are the first sign of extranodal metastatic disease, particularly in patients with melanoma, breast cancer, or mucosal cancers of the head and neck.

Cytokeratin 20: a marker for diagnosing Merkel cell carcinoma.

Merkel cell carcinoma is an aggressive cutaneous neoplasm that is often difficult to diagnose because of its histologic and immunohistochemical similarity to metastatic oat cell carcinomas and other cutaneous neoplasms. Our purpose was to determine the utility of immunoperoxidase staining of cytokeratin 20 (CK 20), a newly discovered intermediate filament protein, in Merkel cell carcinomas and other cutaneous tumors. Sixty-one tumors were sectioned and stained with antibodies directed at CK 20. The staining of Merkel cell carcinomas was compared with metastatic oat cell carcinomas, lymphomas, squamous cell carcinomas, basal cell carcinomas, melanomas, metastatic carcinoids, spiradenomas, eccrine carcinomas, adenoidcystic carcinoma, sebaceous carcinomas, hidradenomas, sebaceous epitheliomas, trichoblastomas, mixed tumors, and metastatic adenocarcinomas. Nine of 10 Merkel cell carcinomas stained with antibody to CK 20. Two metastatic carcinomas to the skin were also positive. One hidradenoma and one squamous carcinoma exhibited focal staining, but were otherwise negative. All other tumors were nonstaining. Cytokeratin 20 is a sensitive and specific marker for Merkel cell carcinoma and is helpful in distinguishing between Merkel cell carcinoma and other malignant and benign neoplasms.

A clinical and histopathologic study of granulomatous rosacea.

A retrospective clinical and histopathologic study of 53 patients with granulomatous rosacea was undertaken. The patients had a broad clinical spectrum of lesions that ranged from primarily erythema to papulonodular lesions. Extrafacial lesions occurred in 15% of patients. Histologic examination showed mixed lymphohistiocytic inflammation (primarily lymphocytic inflammation in 40% of patients and primarily histiocytic with a few giant cells in 34%), epithelioid granulomas in 11% of patients, and epithelioid granulomas with caseation necrosis in 11%. Most patients had a good response to oral antibiotic therapy. Granulomatous rosacea is not a distinct disease but can be regarded and treated as a subtype of rosacea.

Interstitial granulomatous dermatitis with arthritis

BACKGROUND Interstitial granulomatous dermatitis with arthritis is an uncommon systemic disorder involving the cutaneous and musculoskeletal systems. The eruption may mimic other dermatoses including granuloma annulare, erythema chronicum migrans, and the inflammatory stage of morphea. Key histopathologic characteristics, along with clinical correlation, allow accurate diagnosis. OBJECTIVE We describe the clinical, serologic, and histologic features in three patients with interstitial granulomatous dermatitis with arthritis. METHODS Skin biopsy specimens were examined and correlated with the clinical and laboratory findings. RESULTS Erythematous, annular, indurated plaques on the extremities were present in two women. An erythematous, papular eruption on the head and neck was present in a third patient. All patients had myalgia and migratory polyarthralgias of the extremities along with various serologic abnormalities. Histologic examination revealed a dense lymphohistiocytic interstitial infiltrate involving primarily the reticular dermis. Foci of necrobiotic collagen were present. Vasculitis was absent. CONCLUSION Interstitial granulomatous dermatitis with arthritis is unique multisystem disease with variable cutaneous expression. Abnormal serologic findings indicate a possible connection to collagen vascular disease.

Detection of HSV-specific DNA in biopsy tissue of patients with erythema multiforme by polymerase chain reaction

Formalin‐fixed paraffin‐embedded skin biopsies of lesions of erythema multiforme (EM) from 32 patients and 13 controls were examined for the presence of herpes simplex virus (HSV) by polymerase chain reaction (PCR) and for histological findings by direct immunofluorescence and staining with haematoxylin and eosin. HSV‐specific DNA was detected in 23 (72%) patients. A history of recurrent skin rash was present in 59% of the PCR‐positive cases, while 55% had had suspected HSV infections. Only two PCR‐positive specimens were found in patients without a history of recurrent rash and/or previous oral lesions. One biopsy was positive for HSV by conventional cell cultures. There was no significant difference in histology between HSV‐related and HSV‐negative cases of EM. In the 13 control specimens [bullous pemphigoid (3), dermatitis herpetiformis (2), lichen planus (1), aphthous ulcer (1), fixed‐drug eruption (1), varicella‐zoster (1), hypereosinophilic syndrome (1), photocontact dermatitis (1), contact dermatitis (1), and cellulitis (1)], no HSV‐DNA was detected.

Immunohistochemical stains in extramammary Paget's disease

The histologic and immunohistochemical characteristics of 49 skin biopsy specimens from 49 patients with extramammary Pagets disease were studied. Patients with extramammary Pagets disease with and without underlying malignant disease were identified. Associated malignant lesions, present in 16 patients (33%), were transitional cell carcinoma of the bladder (n = 8), adenocarcinoma underlying the skin (n = 3), adenocarcinoma of the anus (n = 1), adenocarcinoma of the vulva (n = 1), apocrine carcinoma (n = 1), prostate carcinoma (n = 1), and carcinoma metastatic to the lung (n = 1). The main histologic feature was the presence of Pagets cells, predominantly at the base of the epidermis. In 6% of the cases, well-defined nests of large Pagets cells mimicked melanocytic nests. Carcinoembryonic antigen and Cam 5.2 (a monoclonal antibody that stains 40-kDa, 45-kDa, and 52.5-kDa low molecular weight keratins) were localized to the Pagets cells in 42 of 45 (93%) and 29 of 41 cases (71%), respectively. Forty-four of 46 lesions (96%) were mucin positive, as determined by Hales colloidal iron stain. Absence of staining for colloidal iron and carcinoembryonic antigen occurred somewhat more frequently in patients with underlying malignant disease than in patients without tumors (13% vs. 0% mucin negative and 13% vs. 3% carcinoembryonic antigen negative, respectively). Although immunohistochemical staining for low molecular weight keratin may be used to confirm the diagnosis of extramammary Pagets disease, Cam 5.2 is not as sensitive as the colloidal iron or carcinoembryonic antigen stain.

Granulomatous slack skin: a clinicopathological and immunohistochemical study of three cases.

Three cases of granulomatous slack skin (GSS), a rare variant of T‐cell lymphoma, are reported. Immunohistochemical studies using a panel of 16 antibodies were carried out on both frozen tissue and tissue embedded in paraffin wax to characterize the infiltrate. A routine immunoperoxidase technique was used to identify T cells (UCHL1, CD45RO), B cells (L26, 4KB5 [CD45R]). S100 protein‐positive cells, monocytes/macrophages (Mac‐387, KP1 [CD68]), and dermal dendrocytes (factor XIIIa) in paraffin sections. A close association was found between UCHL1‐positive T cells and KP1‐positive giant cells. A number of S100‐positive cells and factor XIIIa‐positive cells were present in the infiltrate from all three patients. The lymphocytes in two of the patients were predominantly of the helper T‐cell phenotype. Giant cells from all three patients stained with KP1 (CD68) and Leu M3 (CD14). These studies confirm that the infiltrate in GSS is predominantly a T‐cell disorder associated with monocyte‐derived cells rather than with resident dendritic macrophages.

Immunohistochemistry of pigmented actinic keratoses, actinic keratoses, melanomas in situ and solar lentigines with Melan‐A

Distinguishing lentigo maligna from solar lentigo, and pigmented actinic keratosis can sometimes be problematic. Melan‐A is an immunohistochemical marker which that can be helpful in decorating the melanocytes of pigmented lesions. A recent report has suggested that Melan‐A may spuriously label nests of junctional keratinocytes, potentially leading to the misdiagnosis of melanoma in situ. We compared Melan‐A immunohistochemical staining in pigmented actinic keratosis , non‐pigmented actinic keratoses , melanoma in situ of lentigo maligna type and solar lentigines. We found a statistically significant increase of Melan‐A staining in melanoma in situ, but no statistical difference in the number of junctional Melan‐A positively staining cells, in solar lentigines, pigmented actinic keratoses, and non‐pigmented actinic keratoses, respectively. In the non non‐melanoma samples, the Melan‐A A‐positive cells located at the dermal‐epidermal junction were interspersed and not observed in clusters. Increased staining with Melan‐A, in an actinic keratosis, or solar lentigo should raise the possibility of a contiguous melanoma in situ.

Multiple familial trichoepitheliomas: a folliculosebaceous-apocrine genodermatosis.

We reviewed the pathologic findings on a family with multiple hereditary trichoepitheliomas. Although the majority of the lesions were trichoepitheliomas, basal cell carcinomas, spiradenomas, and spiradenomas with cylindromatous foci (spiradenocylindroma) were present, representing a spectrum of lesions exhibiting folliculosebaceous (trichoepithelioma, basal cell carcinoma) and apocrine (spiradenoma, spiradenocylindroma) differentiation. Multiple familial trichoepitheliomas may be a syndrome whereby tumors develop from undifferentiated germinative cells of the folliculosebaceous-apocrine unit. Published findings regarding the genetics of this syndrome and solitary trichoepitheliomas are reviewed; although the molecular basis for the tumors has yet to be determined, current data suggest that a tumor suppressor gene may be involved.

Malignant melanoma with clinical and histologic features of Merkel cell carcinoma

We describe a patient with malignant melanoma that resembled a Merkel cell carcinoma both clinically and histologically. Immunohistochemical studies showed focally positive staining with S-100 protein and strongly positive staining with HMB-45. Ultrastructural study confirmed the diagnosis by demonstrating premelanosomes and melanosomes. Although the tumor appeared to be clinically unimpressive, it was a deep melanoma with a Breslow level of 3.8 mm that necessitated aggressive treatment. Small cell melanoma must be considered in the differential diagnosis of small cell tumors, which also includes lymphoma, eccrine carcinoma, squamous cell carcinoma, and Merkel cell carcinoma. The diagnosis of amelanotic melanoma, including the small cell variant, may require electron microscopic studies.