Benign cutaneous Degos' disease: a case report with emphasis on histopathology as papules chronologically evolve.

The following case report details a 53-year-old man with a 6-year history of the benign cutaneous or skin-limited form of Degos' disease. Clinically, the patient demonstrated a diffuse eruption of papules on the upper trunk and arms. Many papules demonstrated the classic porcelain-white centers characteristic of Degos' disease, but others exhibited different clinical morphologies that corresponded to the evolutionary stages of papules originally described by Degos. Over the course of several clinic visits, the patient underwent a total of 5 punch biopsies, the histologies of which were correlated with their clinical morphologies. Early papules were skin-colored and demonstrated a superficial and deep perivascular, periadnexal, and perineural chronic inflammatory cell infiltrate associated with interstitial mucin deposition. The overlying epidermis showed a mild vacuolar interface reaction and the histologic appearances at this early stage resembled tumid lupus erythematosus. Fully developed papules were raised with umbilicated porcelain-white centers and a surrounding erythematous rim. Histologically these exhibited a prominent interface reaction with squamatization of the dermo-epidermal junction, melanin incontinence, epidermal atrophy, and a developing zone of papillary dermal sclerosis that resembled the early stages of lichen sclerosus et atrophicus in miniature. These interface reactions were invariably confined to the central portion of the punch biopsy specimen, corresponding to the central porcelain-white area seen clinically. Additional features of fully developed papules included a prominent lymphocytic vasculitis affecting venules, a mild periadnexal infiltrate of neutrophils and/or eosinophils, and interstitial mucin deposition. In late-stage papules, the porcelain-white areas were better developed and the lesion flattened. Histologically, the degree of inflammation was generally sparse and the overall picture mirrored the classic histologic description of Degos' disease with a central roughly wedge-shaped zone of sclerosis surmounted by an atrophic epidermis and hyperkeratotic compact stratum corneum. These late-stage papules closely resembled a miniaturized version of fully developed lichen sclerosus et atrophicus confined to the center of the punch biopsy specimen.

Composite dendritic cell neoplasm (NOS) and small lymphocytic lymphoma.

This report describes a composite (or "collision") of a dendritic cell neoplasm and small lymphocytic lymphoma. It represents the seventh example of dendritic cell neoplasia occurring in the setting of low-grade B-cell malignancy and the third example of a composite tumor, in which both neoplasms were present within the same lymph node. The small lymphocytic lymphoma component exhibited a typical CD20+, CD5+, and CD23+ immunophenotype. The dendritic cell neoplasm exhibited reactivity with CNA-42, but nonreactivity for CD21, CD35, smooth muscle actin, desmin, and epithelial membrane antigen (EMA). Equivocal cytoplasmic staining was seen for S100p, CD68, and Factor XIIIa. Ultrastructurally, the dendritic cell neoplasm exhibited desmosomes, rough endoplasmic reticulum, cytoplasmic intermediate filaments, and intercellular collagen. Because the immunophenotype and ultrastructure did not correspond to one of the five recognizable dendritic cell subtypes, the neoplasm was designated dendritic cell neoplasm, not otherwise specified (NOS). Polymerase chain reaction (PCR) analysis for immunoglobulin heavy chain gene rearrangements performed on individual components of the composite tumor demonstrated rearrangement within the small lymphocytic lymphoma component, but none in the dendritic cell component. The lack of an immunoglobulin heavy chain gene rearrangement within the dendritic cell component argues against a transformational event and supports the concept that these separate neoplasms represent a true "collision" or composite lesion.

Increased sensitivity of the BACTEC 460 mycobacterial radiometric broth culture system does not decrease the number of respiratory specimens required for a definitive diagnosis of pulmonary tuberculosis.

The BACTEC 460 radiometric mycobacterial broth culture system has consistently demonstrated faster and increased recovery of Mycobacterium tuberculosis from respiratory specimens of patients with pulmonary tuberculosis than conventional culture methods. We thus questioned whether three sputa were still necessary to definitively diagnose pulmonary tuberculosis if the BACTEC radiometric culture system were in use. We performed a retrospective analysis of 430 sequential respiratory specimens submitted from 143 patients and from which M. tuberculosis had been recovered by in vitro culture and simultaneously assessed the diagnostic yield of acid-fast smear in this same cohort. M. tuberculosis was recovered from the first specimen for 117 (82%) of the 143 patients, from the second for 14 patients (10%; cumulative rate, 92%), and from the third for 12 patients (8%; cumulative rate, 100%). With the exception of those for bronchial brushings, recovery rates of M. tuberculosis were comparable for all respiratory specimen types (expectorated sputum, induced sputum, tracheal aspirates, bronchoalveolar lavage fluids). Only 46 (32%) of these 143 patients had acid-fast bacilli detected in smears; acid-fast bacilli were detected in the first submitted specimen for 44 patients (96%) and in the second for the remaining 2 patients (4%; cumulative rate, 100%). Culture- or smear-positive rates for sequential specimens obtained from AIDS patients were comparable to those for non-AIDS patients. Overall, the diagnostic culture yield of sequentially submitted specimens was not different from previously published studies in which the BACTEC radiometric culture system had not been used. Despite the documented enhanced ability of the BACTEC 460 radiometric mycobacterial culture system to recover M. tuberculosis more often and faster than conventional methods, three sequential respiratory specimens (regardless of type) were still necessary to definitively diagnose pulmonary tuberculosis.

Cutaneous aspergillosis and acquired immunodeficiency syndrome.

BACKGROUND: Primary cutaneous aspergillosis is an uncommon finding in patients with acquired immunodeficiency syndrome (AIDS); only 13 cases have been reported in the literature. OBSERVATIONS: We describe 11 patients with primary cutaneous aspergillosis and AIDS. There does not seem to be an age, sex, race, or human immunodeficiency virus risk factor predisposition. This is a late manifestation of AIDS; patients typically have low CD4 counts (<0.050 x 10(9)/L [<50/microL]) and other AIDS-defining illnesses. The most frequent presentation is in patients with cytomegalovirus disease and neutropenia caused by ganciclovir therapy. Lesions developed at the site of occlusive dressings for an indwelling intravenous catheter site in 10 patients. Neutrophil counts may be normal at the time of diagnosis. A minor presentation is in the patient without neutropenia as a result of traumatic inoculation. Histological findings and/or culture results are required for diagnosis. Patients develop cutaneous lesions despite prophylactic therapy with fluconazole. Lesions can be treated with excision and lifelong therapy with itraconazole. CONCLUSION: Because of the potential morbidity and mortality of cutaneous aspergillosis, a high level of suspicion and prompt institution of therapy is required.

Epithelioid blue nevus: neoplasm Sui generis or variation on a theme?

The epithelioid blue nevus has recently been associated with the Carney complex, which is characterized by myxomas, spotty skin pigmentation, endocrine overactivity, and schwannomas. Using the general criteria proposed by Carney and Ferreiro, similar lesions were identified in 33 patients with no evidence of the Carney complex. Those lesions presented on the face, trunk and extremities of 15 males and 18 females. The mean age was 35 years, much older than those in the Carney complex (mean 16.3 years). Clinical diagnoses included malignant blue nevus, atypical nevus, melanoma, congenital nevus, and dermatofibroma. The lesions were symmetric, predominantly dermal melanocytic proliferations arranged as short fascicles, small nests, and single cells. Large polygonal and epithelioid melanocytes with moderate pleomorphism, and occasional nuclear pseudoinclusions were admixed with heavily pigmented dendritic and spindled melanocytes and melanophages. Rare mitotic figures were seen in some cases. The neoplasms showed a morphologic spectrum that encompassed a group of combined blue nevi with epithelioid melanocytes and other Spitz's nevus characteristics. These epithelioid combined nevi (ECN) fell into three phenotypes with morphologies that most closely paralleled those pictured by Carney and Ferreiro in the Carney complex: the classic or Carney complex pattern (ECN-CC), those that showed overlap with deep penetrating nevus (ECN-DPN), and those that have many dermal Spitz's nevus features, [BLue + SpITZ's nevus; (ECN-BLITZ)I. In six cases, there was such an admixture of features that it was difficult to ascribe them to one of the groups. Nine lesions had associated banal congenital nevus. Follow-up that averaged over 2.5 years (31 months) (range 6-162 months) showed no evidence of malignancy or recurrent disease after excision. Epithelioid combined nevus is a type of combined nevus with blue nevus and Spitz's nevus features, which may or may not be associated with the Carney complex. It shows morphologic overlap with the epithelioid blue nevus described by Carney (ECN-CC), deep penetrating nevus (ECN-DPN), and blue nevus with intradermal Spitz's (desmoplastic) nevus (ECN-BLITZ). Epithelioid combined nevus is thought to be a fitting nosologic designation for all of these lesions.

Persistent and recurrent blue nevi.

Persistence of common melanocytic nevi has been fairly well characterized, clinically and histologically. In contrast, persistence of blue nevi has been reported infrequently. To define this entity better, nine cases of biologically persistent and clinically recurrent blue nevi are described. The persistent lesions in four cases were spindle-fascicular blue nevi; one showed senescent or "ancient" change and one had additional deep penetrating/epithelioid blue nevus features with atypical changes worrisome for malignancy. These changes included increased cellularity, cellular pleomorphism, mitotic figures, and a lymphocytic infiltrate. Three were biphasic dendritic-sclerotic/spindle-fascicular blue nevi, one of which had atypical changes. One case was a dendritic-sclerotic ("common") blue nevus. The original histology in one case was unavailable, but the recurrence was a combined blue nevus. The interval from initial biopsy to biopsy of the recurrent lesion was often longer (mean 2.7 years) for recurrent blue nevi than for recurrent common compound or intradermal melanocytic nevi. In addition, in contrast to recurrent common melanocytic nevi, the recurrence, in at least one case, extended beyond the scar of the original excision. These cases demonstrated that blue nevi of all histiotypes and combinations are capable of persistence with clinical recurrence. The persistence usually was histologically similar to the original, but in some cases was more "cellular" because, for the most part, the excisions of the persistent lesion revealed a deeper spindle-fascicular ("cellular") component not evident in the original superficial biopsy. In two cases, the original blue nevus appeared completely banal, but the persistent/recurrent lesions were histologically distinct and demonstrated atypical histologic features. Yet, follow-up (average 3.7 years) supports benign biology. Clinical recurrence is often associated with malignant transformation in blue nevus, but this series demonstrates that malignant tumor progression is not necessarily the case. In the absence of necrosis en mass, marked cytologic atypia, and frequent mitotic figures, the described atypical morphologic parameters in previously biopsied small blue nevi are probably reactive and "pseudomalignant." Awareness of this potential change may avoid diagnostic and prognostic errors.

Histogenetic relations between giant cell fibroblastoma and dermatofibrosarcoma protuberans. CD34 staining showing the spectrum and a simulator.

The authors describe three lesions that provide further evidence for a close, possibly histogenetic relation between giant cell fibroblastoma and dermatofibrosarcoma protuberans. The first case involves a dermatofibrosarcoma protuberans that contained a single giant cell fibroblastoma-like focus of multi-nucleate giant cells. A second tumor, a giant cell fibroblastoma, recurred 6 years later as a dermatofibrosarcoma protuberans. In the third lesion, there was a juxtaposition and co-mingling of dermatofibrosarcoma protuberans and giant cell fibroblastoma within the same primary lesion. In all cases, both the giant cell fibroblastoma areas and dermatofibrosarcoma protuberans areas stained positively with CD34. A fourth case, a dermatofibrosarcoma protuberans infiltrated skeletal muscle, creating giant cell fibroblastoma-like giant cell mimics--a result of skeletal muscle degeneration or atrophy with nuclear conglomeration. The latter giant cells failed to express CD34 but did show immunoreactivity with desmin. These findings support the concept that giant cell fibroblastoma and dermatofibrosarcoma protuberans probably represent a histologic spectrum of a single CD34 positive (perhaps, dermal dendrocytic) neoplasm, a conclusion supported by a recently cloned t(7;22) breakpoint demonstrated in both neoplasms.

Grover's-like disease in the setting of bone marrow transplantation and autologous peripheral blood stem cell infusion.

Four cases of a Grover's-like disease in patients with leukemia/lymphoma, who underwent high-dose chemotherapy and either allogeneic/autologous bone marrow transplantation or autologous stem cell infusion, are described. Three of four patients had fever prior to the onset of their rash. In addition to suprabasilar clefts, acantholysis, and dyskeratosis, typical of Grover's disease, there was a chemotherapeutic effect in the form of keratinocytes with atypical nuclei. So-called "starburst cells," which have been purported to be specific for high-dose etoposide (VP-16) therapy, were seen in two cases, but only one of these patients received etoposide. In one patient with clinical vesicles, direct immunofluorescence ruled out paraneoplastic pemphigus. In conjunction with 18 similar cases in the literature, the following conclusions were reached: (a) the pathogenesis probably involves the combined effects of fever (with sweating), occlusion, and chemo/radiation therapy; (b) no single chemotherapeutic agent can be consistently implicated; and (c) in addition to graft-versus-host disease, the eruption of lymphocyte recovery, and other cutaneous eruptions in the setting of bone marrow transplantation, the differential diagnosis includes paraneoplastic pemphigus, which direct immunofluorescence excludes.

Spitz's nevi with halo reaction: a histopathologic study of 17 cases.

Halo reactions to melanocytic nevi are a well-recognized phenomenon. In contrast, halo reactions to Spitz's nevi have been reported only infrequently. Halo reactions may cause misdiagnosis of an otherwise benign nevus as melanoma because inflammatory cells sometimes obscure the architectural features of the underlying nevus, and may induce cytologic atypia. For Spitz's nevus where the distinction between malignancy and benignancy is already challenging, halo reactions compound the problem. We describe 17 examples of Spitz's nevus with halo reaction, and compare their immunohistochemical features with those of "ordinary" halo nevi. Only 2 of 17 lesions demonstrated clinically apparent halos. Clinical follow-up was available for 12 of 17 cases. None of the 12 has persisted at the biopsy site or metastasized after an average 3.6-year follow-up period. Junctional, compound, intradermal, and combined types of Spitz's nevi were represented. All were characterized by symmetrical lymphocytic infiltrates which permeated the full thickness of the nevus, including junctional nests. Combined Spitz's nevi constituted more than one-half of examples in this series (9/17 cases). The combined Spitz's nevus included a combination of Spitz's nevus with either an ordinary (common, banal) nevus or a superficial congenital type nevus. In these combined Spitz's nevi, the lymphocytic response was often directed exclusively to the Spitz's nevic component. Important distinguishing features from malignant melanoma arising in a pre-existing nevus included symmetry and lateral circumscription of the spitzoid component, no large expansile-appearing aggregates of melanocytes, a decrease in size of nests with increasing dermal depth, a lack of mitotic figures among melanocytes at the base, and a symmetrical and diffusely permeative lymphocytic response. Although the combined Spitz's nevus with halo reaction sometimes appeared asymmetrical at scanning magnification, each component of the combination was symmetrical, when examined independently. Probably because of reactive atypia, nuclear maturation with progressive descent into the dermis was sometimes absent. There were no obvious differences in immunohistochemical staining patterns among 4 Spitz's nevi with halo reaction, 5 regressing melanomas, and 5 benign halo nevi when stained with antibodies to S100, HMB-45, OPD4, CD8, TIA-1, CD1a, CD68, and Ki-67.

Isolated intra-abdominal esophageal cyst. Case report and review of the literature.

We describe the first case of an isolated intra-abdominal esophageal cyst. The cyst was unilocular, smooth-surfaced, and attached to the superior border of the pancreas, and it contained clear mucoid material. The gross and in situ features most closely resemble four previously reported cases of isolated intra-abdominal bronchogenic cyst. Histologically, the cyst contained a simple and pseudostratified, ciliated, mucus-secreting, columnar epithelium and a wall composed of two distinct layers of smooth muscle. Both bronchogenic cysts and esophageal cysts may have ciliated epithelium; however, the presence of two smooth-muscle layers, along with the absence of cartilage or respiratory glands, allows for a definitive diagnosis of esophageal cyst.

Eccrine or apocrine poroma? Six poromas with divergent adnexal differentiation.

We describe six cases of benign eccrine poroma-like neoplasms with divergent adnexal differentiation. Four cases exhibited sebaceous differentiation in the form of individual or clustered sebocytes with or without sebaceous ducts. One case showed both sebaceous and hair follicle differentiation, and one case showed sebaceous and possible apocrine secretory differentiation. Clinically, most were skin-colored, red, or purple papules or nodules. One patient had a preoperative diagnosis of Bowen's disease, with an erythematous plaque. None recurred following biopsy. Previous reports of similar lesions have suggested a possible role for human papilloma virus (HPV) in their pathogenesis; however, immunohistochemical staining for HPV structural antigens was negative in all six of these cases. Similarities to previously reported cases of eccrine poroma-like neoplasms with sebaceous differentiation are discussed. Given the evidence of sebaceous and follicular differentiation seen in this study and the common embryologic origin of follicular, sebaceous, and apocrine structures, it follows that at least some benign neoplastic proliferations with histopathologic features of "eccrine" poroma could be of apocrine origin.

Percutaneous absorption and inflammation in aged skin: a review.

We review experimental studies that address age-related changes in cutaneous barrier function and dermal blood vessel function. These differences have important implications in the understanding of age-related changes in the inflammatory process and topical drug delivery systems.

Effect of organic solvents on in vitro human skin water barrier function.

Skin barrier disruption caused by organic solvents to human cadaver dermatomed skin was evaluated using an in vitro model system. Resultant changes in transepidermal water loss (TEWL), as measured with an evaporimeter, were recorded after topical application of either acetone, chloroform:methanol 2:1, hexane, hexane:methanol 2:3, or the control, water, for exposure times of 1, 3, 6, and 12 min. The resultant lipid/solvent mixture was removed and analyzed for its lipid content. The ability of the different solvents to induce changes in the skin's barrier function was assessed by comparing pre- to post-solvent exposure TEWL (delta TEWL). When compared to the controls, water and unexposed skin, chloroform:methanol 2:1 caused the greatest significant increase in TEWL, followed by hexane:methanol 2:3. Acetone and hexane showed no difference in TEWL from the controls. Besides solvent, exposure time was a significant independent variable for predicting delta TEWL, and the interaction of the two (exposure time and solvent type together) was the strongest predictor. Lipid analysis of the extracts revealed that all the solvents removed comparable quantities of the surface lipids (triglycerides, wax esters, squalene, cholesterol esters). Stratum lipids--ceramides, free fatty acids, and cholesterol--extracted by chloroform:methanol 2:1 and hexane:methanol 2:3 were comparable and significantly greater than those extracted by acetone and hexane. These two solvents failed, however, to induce comparable changes in TEWL, as chloroform:methanol 2:1 induced a significantly greater delta TEWL than hexane:methanol 2:3. Additionally, no individual lipid class extracted by either chloroform:methanol 2:1 or hexane:methanol 2:3 proved to be a significant or accurate variable for predicting delta TEWL. This suggests that the mechanism by which topical chloroform:methanol 2:1 and hexane:methanol 2:3 exposure induce a delta TEWL involves more than pure lipid extraction.