Extranodal marginal zone B-cell lymphoma of the skin: a morphologic and immunophenotypic study of 11 cases.

Extranodal marginal zone B-cell lymphoma (MZBL) is a recently recognized low-grade lymphoma that has been well described in other organs such as the stomach and salivary gland. It has only recently been described in skin, where it may be difficult to distinguish from reactive processes and other types of B-cell lymphoma such as follicle center lymphoma. These cases may have been classified as pseudolymphomas in the past. Extranodal MZBL was referred to as mucosa-associated lymphoid tissue (MALT) lymphoma before the Revised European-American Classification of Lymphoid Neoplasms was published in 1994. Important histologic features that aid in the diagnosis of MALT lymphoma are atypical lymphocytes (centrocyte-like and monocytoid B cells) often admixed with plasmacytoid lymphocytes, a prominent plasma cell component, lymphoepithelial lesions, intranuclear inclusions (Dutcher bodies), and reactive germinal centers that may be colonized by neoplastic cells. Immunophenotypic studies demonstrating a B-cell phenotype, light chain restriction, coexpression of CD43, and staining of atypical lymphocytes with bcl-2 support a diagnosis of MALT lymphoma. We studied 11 cases of extranodal MZBL of the skin from the Armed Forces Institute of Pathology files. There were six women and five men ranging in age from 30 to 69 years (median, 54 years). The anatomical sites included the trunk, head and neck areas, and upper extremities. There were no other sites of disease besides the skin in any of the cases. The follow-up period ranged from 5 months to 8 years (median, 24 months). Histologic results included an atypical lymphoid infiltrate with B-cell phenotype, reactive germinal centers, and a variable plasma cell component in all cases. No Dutcher bodies or lymphoepithelial lesions were noted. Extranodal MZBL of skin is a diagnostic challenge because of a heterogeneous cellular infiltrate that may be interpreted as a reactive process. The most significant neoplasm with which it is confused is follicular lymphoma. It is important to recognize the characteristic histologic and immunophenotypic features of extranodal MZBL so that the appropriate therapeutic approach may be applied.

Aggressive digital papillary adenocarcinoma (aggressive digital papillary adenoma and adenocarcinoma revisited).

In 1987 a clinicopathologic study by the Armed Forces Institute of Pathology (AFIP) of rare sweat gland tumors, termed aggressive digital papillary adenoma and adenocarcinoma, was published. Since that time, the AFIP has continued to collect these tumors for study. Based on additional follow-up data, we think the original classification of these tumors requires revision. Sixty-seven cases of aggressive digital papillary adenoma and adenocarcinoma were studied according to their clinical characteristics and histologic features. Fifty of these were originally diagnosed as adenoma and 17 as adenocarcinoma. Follow up on 45 (67%) of the patients was obtained. None of the clinical or histologic parameters studied were found to be predictive of recurrence or metastasis, indicating that the originally proposed criteria for distinguishing between benign (adenoma) and malignant (adenocarcinoma) do not predict biologic behavior. When primary tumors were treated by subsequent reexcision or amputation, only one recurred (5%), when not so treated, 11 recurred (50%) regardless of the original diagnosis (p <0.05). Metastasis occurred in six (14%) cases and in three cases led to the death of the patient. Three of these metastatic cases had met the earlier criteria for adenoma. Pulmonary metastases were observed in five cases. No effective treatment for widespread metastatic disease has yet been developed. Because histologic features with prognostic significance could not be demonstrated in this retrospective review, we propose that all aggressive digital papillary tumors be designated aggressive digital papillary adenocarcinoma.

Primary cutaneous Ki-1(CD30) positive anaplastic large cell lymphoma in childhood.

Primary cutaneous Ki-1(CD30) positive anaplastic large cell lymphoma (ALCL) is an unusual tumor in the pediatric population. However, the nodal-based form of the disease compared with other histologic subsets of childhood non-Hodgkin's lymphomas (NHL) more frequently involves skin, soft tissue, and bone. The objective of this article is to determine the histologic and immunologic characteristics of childhood primary cutaneous Ki-1(CD30) positive ALCL and its prognosis. The clinical data, histologic features and immunohistochemical profiles of skin biopsy specimens from 3 children with cutaneous Ki-1(CD30) positive lymphoma were reviewed. A literature search was performed and disclosed information on 5 childhood cases. The 3 patients with primary cutaneous Ki-1(CD30) positive ALCL all presented similarly as rapidly growing masses initially and clinically believed to be infectious/reactive processes. The diagnosis was established on the basis of histopathologic examination and immunohistochemical studies. Histologic sections revealed an extensive infiltrate of tumor cells extending throughout the entire dermis into the subcutaneous fat with frank ulceration in 1 patient. No significant epidermotropism was noted. Tumor cells exhibited striking cellular pleomorphism and a high mitotic rate with numerous atypical mitoses. Inflammatory cells were present in all patients. The tumor cells stained positively for Ki-1 antigen (CD30), epithelial membrane antigen, and for T-cell markers (UCHL-1, CD3). One of 3 cases, however, failed to stain for leukocyte common antigen (LCA). No clinically apparent adenopathy was observed in any of the patients. In all instances the patients developed recurrent disease in the skin at sites separate from the primary location. None of the patients demonstrated any involvement of lymph nodes, bone marrow, or other organ systems. All patients were treated with chemotherapy with good response. Primary cutaneous Ki-1(CD30) positive lymphoma is rare in children and is characterized by recurrences. The prognosis seems to be favorable.

Eosinophilic globules in spindle cell and epithelioid cell nevi: composition and possible origin.

The presence of eosinophilic globules has been described as a helpful sign for the histologic differentiation of Spitz's nevus from malignant melanoma. The origin of these bodies is not clear, and they have been likened to Civatte or colloid bodies of lichen planus. This would suggest that they might originate from degenerating keratinocytes or melanocytes or both. These eosinophilic globules and the colloid bodies of lichen planus have been reported to be similar in that they both stain positively for type IV collagen and laminin. These previous reports have failed to include, or have not emphasized, the staining for keratin that separates these two bodies. We stained 10 spindle cell and epithelial cell (S&E) nevi for S-100 protein, keratin, vimentin, type IV collagen, and laminin. In all 10 cases of S&E nevi, the eosinophilic globules showed a positive reaction for type IV collagen and laminin and a negative reaction for keratin, S100 protein, and vimentin, unlike the colloid bodies of lichen planus, which showed a negative reaction for type IV collagen and laminin and also a strong positive reaction for keratin. These results suggest that the eosinophilic globules of Spitz's nevi are basement membrane material, perhaps synthesized by either basal cells, melanocytes or both, and are not degenerated basal cells or melanocytes.

Unusual expression of S-100 protein in histiocytic neoplasms.

Twenty-nine cases of histiocytic neoplasms, some resembling juvenile xanthogranuloma (JXG) and others resembling reticulohistiocytoma (RH), were evaluated. Immunohistochemical stains were performed. In this series, seven cases were identified that expressed S-100 protein positive cells. The S-100 positive cells were predominantly large mononuclear and multinucleated histiocytes with eosinophilic cytoplasm, but also in some cases xanthomatous cells and Touton giant cells. These cells also expressed a positive reaction for vimentin, KP-1, and Factor XIIIa. There was no reactivity observed for monoclonal antibody 010(CD1a). A positive reaction for S-100 protein is conventionally accepted as a useful differentiating feature between histiocytosis X and non-X histiocytosis such as JXG and RH. The conflicting results of the immunohistochemical stains in the lesions we studied could be potential pitfalls in diagnosing histiocytic neoplasms.

Nodular melanosis due to epithelial neoplasms: a finding not restricted to regressed melanomas.

Nodular or tumoral melanosis consists of nodular or sheetlike deposits of melanophages in the dermis. When nodular melanosis is present, a completely regressed malignant melanoma is a major diagnostic consideration. We present a case of nodular melanosis due to regression of a pigmented basal cell carcinoma with pilar differentiation. In addition to this case, we present five additional cases of epithelial neoplasms with melanin deposition in the stroma. In each case, the source of the melanin was non-neoplastic dendritic melanocytes intermingled among the tumor cells. Therefore, if nodular melanosis is found, pigmented epithelial neoplasms should also be considered in the differential diagnosis.

Cytokeratin 7 staining in mammary and extramammary Paget's disease.

There are a variety of routine and immunohistochemical stains used to diagnose mammary and extramammary Paget's disease (MPD and EMPD). Most of the stains commonly used, however, show a positive reaction in the Paget's cells in all cases. We wanted to assess which immunohistochemical stain is the best for the diagnosis of MPD and EMPD, as well as the best stain for identifying small foci of tumors in evaluating tumor margins. We evaluated nine cases of MPD and nine cases of EMPD, which were randomly chosen, with a battery of immunohistochemical stains. These stains included cytokeratin 7, cytokeratin 20, carcinoembryonic antigen, Ber-EP4, and CAM 5.2. Cytokeratin 7 was the only immunohistochemical stain that stained all of the cases diffusely, and, in all of the cases, the staining of the Paget's cell was intense and specific within the epidermis. We concluded that cytokeratin 7 is the immunohistochemical stain of choice in the diagnosis of Paget's disease. Because cytokeratin 7 seems to identify single cells, it might also be valuable in evaluating surgical margins for small foci in a tumor such as EMPD, which might have a multifocal origin.

Merkel cell carcinoma: analysis of clinical, histologic, and immunohistologic features of 132 cases with relation to survival.

BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon malignancy of the skin and has a high rate of recurrence and metastasis. There have been few large studies of the biologic behavior of MCC. OBJECTIVE: Our purpose was to determine whether there were clinical or histologic features of MCC that predict its biologic behavior. METHODS: We reviewed 132 cases of MCC. Clinical and histologic features were correlated with follow-up information to determine whether any of these were associated with prognosis. RESULTS: Clinical information was available on 126 patients; 57 were alive, 1 was alive with tumor, 28 died of tumor, 27 died from other causes, and 14 were lost to follow-up. MCC on the buttock/thigh area or trunk had the worst prognosis, and those on the distal extremities had the best prognosis; however, the difference was not statistically significant. Sex and age were not significant factors. Small cell size, high mitotic rate, and large tumor size were associated with a low survival rate. When cell size was excluded, male sex and depth of invasion were associated with a worse survival, although these were not statistically significant. CONCLUSION: Cell size, mitotic rate, and tumor size are significant factors in relation to the biologic behavior of MCC.

Cutaneous angiosarcomas with a starry-sky pattern.

OBJECTIVE: A subgroup of epithelioid angiosarcomas, which we have identified, has a prominent starry-sky histologic pattern. All these neoplasms were evaluated with routine histopathology and with immunohistochemical stains. Clinical follow-up was also obtained to determine whether these angiosarcomas' had any other distinctive properties. DESIGN: Histopathologic features and immunohistochemical stains, including cytokeratin, epithelial membrane antigen, CD34, LCA, factor VIII-related antigen, KP-1, vimentin, HMB-45, and S100 protein were performed on all four neoplasms. PATIENTS: These angiosarcomas occurred on the extremities of patients with chronic edema as well as on the scalp of elderly patients. MAIN OUTCOME: All patients were dead within 5 years of diagnosis. Of the three patients where angiosarcoma was listed as the cause of death, all were dead within 30 months. RESULTS: All tumors showed a similar immunohistochemical staining pattern. Vimentin, factor VIII-related antigen, and CD34 were positive in all tumors. The remaining immunohistochemical stains including cytokeratin, which may be positive in other epithelioid angiosarcomas, were negative. CONCLUSIONS: We present a distinctive starry-sky histologic pattern in epithelioid angiosarcomas. Knowledge of this pattern may be important in the early diagnosis of this rapidly fatal neoplasm.

Atypical fibroxanthoma. An unusual variant with osteoclast-like giant cells.

We report three cases of an unusual variant of atypical fibroxanthoma with numerous multinucleated osteoclast-like giant cells. Histologically, the lesions were composed of uniformly dispersed multinucleated osteoclast-like giant cells within a pleomorphic cellular proliferation with microscopic and histochemical features of atypical fibroxanthoma. Multinucleated osteoclast-like giant cells, however, stained with KP-1, a macrophage-associated antigen only. These cells are not necessarily an integral part of the tumor and may represent a reactive histiocytic component.

HMB45 negative spindle cell malignant melanoma.

Desmoplastic malignant melanoma (DMM) and spindle cell malignant melanoma (SCMM) form a continuum without a discrete separation. One feature characteristic of DMM is a negative reaction for HMB45, a marker for premelanosomes. Fifty-six cases of SCMM were stained with HMB45. The clinical features, histologic features, and survival data for HMB45(+) and HMB45(-) SCMM were compared. Thirty cases were HMB45(-), and 26 were HMB45(+). In the HMB45(-) cases, there was a 1.4:1 ratio of males to females, and in the HMB45(+) cases the ratio was 1:1.5. Only 12.9% of the HMB45(-) cases occurred on the trunk compared with 40% of the HMB45(+) cases. The average ages for the HMB45(-) and the HMB45(+) cases were 65.6 and 61 years, respectively. Follow-up was obtained on 22 cases: 11 HMB45(-) and 11 HMB45(+). Of the 11 HMB45(-) cases, four had a 5-year disease-free survival. Of the 11 HMB45(+) cases, only one had a 5-year disease free survival. HMB45(-) SCMM appear to have a less aggressive biologic potential than HMB45(+) SCMM.

Protection from radiation-induced alopecia with topical application of nitroxides: fractionated studies.

PURPOSE: Hair loss resulting from irradiation of the head and neck or from whole brain irradiation often leads to cosmetic, social, and psychological problems for the radiotherapy patient. Few successful clinical interventions are available. We have shown that nitroxides (stable free radicals) afford radiation protection against single-dose radiation-induced alopecia in a guinea pig model. Here we determine if topical nitroxide application provides protection from fractionated radiation treatment. MATERIALS AND METHODS: Two symmetrical and contralateral areas (3 x 5 cm) of skin on the dorsal trunk of guinea pigs were shaved to a hair length of 0.25 cm. A 2 mL solution containing 70 mg/mL nitroxide (Tempo or Tempol) in 70% ethanol was topically applied to the skin surface of one side; 70% ethanol was applied to the contralateral (control) side 10 minutes before irradiation. Animals were placed in a special jig that held skin without decreasing blood flow to the treatment area and fractionated external beam radiation (7 Gy) was delivered daily for eight fractions over 10 days via a 4 MeV linear accelerator. Alopecia (hair density) was scored weekly for 13 to 14 weeks after radiotherapy, using a standardized reference with respect to hair loss and regrowth in the treatment field. RESULTS: After radiation treatment, dry desquamation and gradual hair loss were observed for both control and nitroxide-treated skin; however, over weeks 4 to 11 postirradiation hair loss was much more pronounced in control animals when compared with nitroxide-treated animals. Hair density measurements for Tempol treatment over weeks 9 to 13 were approximately 75% compared with measurements in controls of approximately 25%. Tempo-treated animals exhibited hair density values of approximately 90% compared with 12% in controls over weeks 11 to 14. Tempol and Tempo treatments resulted in significant radioprotection. Histologic evaluation showed that radiation treatment alone in ethanol controls resulted in a marked decrease in the number of hair follicles and poor development of remaining follicles; however, nitroxide pretreatment resulted in no appreciable decrease in hair follicles and hair follicles appeared mature. This was also observed in unirradiated ethanol controls. Electron paramagnetic resonance studies revealed that topical nitroxide application did not result in measurable systemic concentrations of either drug. CONCLUSIONS: The results of this study suggest that topical application of nitroxides may be useful in a clinical setting to reduce the undesirable toxicity of radiation-induced alopecia.

A comparison of clinical, morphological and immunohistochemical features of lymphomatoid papulosis and primary cutaneous CD30(Ki-1)-positive anaplastic large cell lymphoma.

The advent of immunoperoxidase technique on paraffin embedded tissue has identified a number of shared immunologic markers present in various lymphoproliferative cutaneous disorders. Two such disorders are the recently described primary cutaneous CD30-positive anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis; both entities are characterized by CD30-positive large atypical cells predominantly of T cell origin. We have compared the clinical, morphological and immunohistochemical features of 50 patients with lymphomatoid papulosis to a group of 27 patients with cutaneous CD30-positive ALCL. There are clear differences between the clinical presentation in these two diseases, and although both are characterized by similar atypical cells, the histologic pattern and distribution of atypical cells is sufficiently different to allow distinction and specific diagnosis based on hematoxylin and eosin stained sections supported by the immunohistochemical stains. In addition, both diseases are characterized by a long benign course, rarely complicated by development of lymphoreticular malignancy and invariably demonstrate CD30 (Ki-1) antigen positive large atypical cells.

Increased anticardiolipin antibodies associated with the development of anetoderma in HIV-1 disease. Military Medical Consortium for the Advancement of Retroviral research (MMCARR).

BACKGROUND AND OBJECTIVE: Anetoderma has been reported in patients with HIV-1 disease. In patients with autoimmune disease, anetoderma has been associated with increased levels of antiphospholipid antibodies (APL) that include anticardiolipin antibodies (ACA) and lupus anticoagulant (LA). This has led to speculation that the autoimmune phenomena seen in HIV-1 disease and the immune dysregulation induced by HIV-1 disease may play a role in the development of these lesions. We have seen both primary and secondary lesions of anetoderma in patients followed for HIV-1 disease. In this study, we wanted to determine whether there was an association in the development of anetoderma and elevated anticardiolipin antibodies (ACA) in HIV-1 patients. METHODS: Quantitative ACA levels were measured in eight HIV-1-infected patients with anetoderma and four HIV-1-infected patients without anetoderma. RESULTS: Anticardiolipin antibodies were moderately elevated in seven of eight patients with lesions and were borderline in the four HIV-1-positive patients without lesions of anetoderma. CONCLUSIONS: There appears to be a correlation between increased ACA and the development of cutaneous lesions of anetoderma in HIV-1 disease. Patterns of immune dysregulation, including APL, may predispose to the development of lesions of anetoderma in HIV-1-positive patients. Although some of the lesions appear to represent primary anetoderma, the majority of our patients develop lesions in areas secondary to well characterized eruptions.

Desmoplastic malignant melanoma.

BACKGROUND: Desmoplastic malignant melanoma (DMM) is an uncommon variant of malignant melanoma and often is difficult to diagnose. Because of the relative rarity of this tumor, it has not been well studied and controversy remains concerning its biologic potential. OBJECTIVE: We compared survival rates of DMM with those of other malignant melanomas and determined what clinical and/or histologic features, if any, correlated with survival. METHODS: The files of the Armed Forces Institute of Pathology were searched for cases of DMM or related tumors with adequate material for further histologic and immunohistochemical evaluation. Follow-up on each patient was requested from the pathologist, clinician, and/or the patient. The follow-up was correlated with the histologic findings in each case. The relationship of histologic features to disease-free survival was evaluated. RESULTS: Adequate material for evaluation was available in 128 cases. The overall histologic features were similar to those previously reported. Immunohistochemical studies showed that all lesions were negative for HMB-45, a marker for premelanosomes. Factors that correlated with survival included tumor location, sex, tumor depth, and the presence of stromal mucin. The 5-year disease-free survival rate was 68% for all cases and 61% for lesions more than 4 mm deep. CONCLUSION: With a 5-year disease-free survival rate of 61%, DMM has a significantly better prognosis than other melanomas that have a 5-year disease-free survival rates of 40% to 41%. This may be related to neural differentiation of these tumors.

Condyloma acuminatum associated with syringocystadenoma papilliferum.

A 70-year-old man presented with a keratotic lesion of the right buttock. Histologic examination revealed an endophytic cystic and papillary lesion of the dermis. The papillae were lined by two layers of cuboidal epithelial cells with a dense plasmacytic infiltrate of the stroma, consistent with syringocystadenoma papilliferum (SCAP). The overlying epidermis showed acanthosis, papillomatosis, and hyperkeratosis. There were multiple foci of prominent koilocytotic atypia. In situ DNA probes for HPV type 6/11 were positive in many epidermal nuclei. The concurrent occurrence of SCAP and CA may be coincidental; however, the occurrence of CA may be related to the environment at the surface of the SCAP. Syringocystadenoma papilliferum often occurs in association with nevus sebaceus (NS), but it has also been reported from most body sites. When it is not seen in association with NS, the epidermis overlying SCAP may be hyperkeratotic or verrucous. The verrucous changes in our case had features of condyloma acuminatum (CA), which were confirmed by in situ DNA probes.

Syringolymphoid hyperplasia with alopecia. A case report.

Syringolymphoid hyperplasia with alopecia is an uncommon skin disorder described in 1969 by Sarkany. Since then only three additional cases have been reported, all in the European literature. We present a 59-year-old man with two persistent hyperpigmented hairless patches of 13 years duration. Biopsy specimens revealed characteristic hyperplastic changes of the eccrine glands and ducts and a dense lymphocytic infiltrate surrounding eccrine structures with "syringotropism". Perifollicular lymphocytic infiltration and changes consistent with follicular mucinosis and mycosis fungoides were also present. Imunophenotyping and gene rearrangement studies showed the cells to be primarily of the T helper phenotype with rearrangement of the surface receptor gene.

Collagenous spherulosis in a schwannoma.

"Collagenous spherulosis" is the term used to describe striking concentric and radiating formations of collagen in tumors. It was originally used for these formations in epithelial tumors of the breast and subsequently in tumors of salivary glands. Recently, the histologic, immunohistochemical, and ultrastructural features were described in a chondroid syringoma. We report a case of collagenous spherulosis in a schwannoma. Routine histologic sections showed a circumscribed tumor in which the predominant feature was radiating fibrillar structures that tended to compress the cellular component of the tumor. Immunohistochemical studies showed that the cells were positive for glial fibrillary acidic protein (GFAP) and S-100 protein but negative for keratin. EMA showed a positive reaction in a thin band of cells around the periphery of the tumor consistent with perineurial cells. Type IV collagen stained around the periphery of the collagen formations. Electron microscopy revealed that the material was consistent with collagen. Our findings were essentially identical to those reported in the chondroid syringoma. This case confirms the findings of the previous study and shows that these unusual formations are not confined to tumors of epithelial origin. Because the architecture of the tumor is distorted, special stains may be required for correct diagnosis.