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Biomedical subjects

B R Smoller

Publications and source records attributed to B R Smoller.

At least 109 records · Page 6Linked to original sources

CD34 staining pattern distinguishes basal cell carcinoma from trichoepithelioma.

BACKGROUND AND DESIGN: Trichoepithelioma is a benign skin tumor with follicular differentiation, which sometimes is difficult to distinguish clinically and histologically from basal cell carcinoma. One of the most helpful differences is the histologic appearance of the stroma. CD34 is an antigen known to stain the spindle-shaped cells located around the middle portion of normal hair follicles. We have stained formalin-fixed, paraffin-embedded sections of 16 trichoepitheliomas and 19 basal cell carcinomas for CD34 (anti-HPCA-1, Becton Dickinson, San Jose, Calif) to detect differences in the staining pattern and to facilitate discrimination of these two types of tumors. RESULTS: The spindle-shaped cells surrounding the islands of trichoepithelioma cells were focally strongly positive for CD34. In all basal cell carcinomas, the spindle-shaped cells surrounding the nests of tumor cells were negative; in these areas only the blood vessels were positive with this antibody. CONCLUSIONS: CD34 staining pattern differentiates between trichoepithelioma and basal cell carcinoma. CD34 stain may be helpful in distinguishing between these two tumors on small punch biopsies or in difficult diagnostic cases.

Antigens, CD↗

Multiple lesions of intravascular papillary endothelial hyperplasia (Masson's lesions).

We recently encountered an elderly female patient with multiple, rapidly growing vascular lesions on her forearm. Histologic examination and immunoperoxidase studies were performed to identify cells present within the lesions. The growths proved to be intravascular papillary endothelial hyperplasia. Immunohistochemical studies showed these lesions to be proliferations of factor VIII+, factor XIIIa+, and CD34+ cells. Intravascular papillary endothelial hyperplasia lesions are growths that histologically can mimic angiosarcoma, especially when they are multiple. They appear to be proliferations of endothelial cells and also contain dermal dendrocytes. This finding raises the question as to the exact origin of the cells that give rise to these tumors.

Aged↗

Immunohistochemistry in the diagnosis of melanocytic neoplasms.

At present the primary role of immunohistochemistry is to define an immunophenotypic profile that is characteristic of melanocytes but rare in other cell types. Its future role may include prediction of how a melanocytic neoplasm will behave. This chapter outlines a strategy for the use of immunohistochemical procedures to identify a neoplasm as melanocytic and discusses the antibodies that are relatively melanoma-specific.

Antibodies, Monoclonal↗

Cutaneous nodules of Mycobacterium chelonae in an immunosuppressed patient with preexisting pulmonary colonization.

A 30-year-old immunocompromised man with known pulmonary Mycobacterium chelonae colonization developed a systemic infection with cutaneous manifestations. The eruption consisted of multiple, nontender, subcutaneous nodules on the extremities. A diagnosis of disseminated M. chelonae was made on the basis of recovery of M. chelonae subspecies abscessus from blood and bronchoalveolar lavage fluid and histologic evidence of acid-fast bacilli in a skin biopsy specimen. We believe this is the first reported case of disseminated M. chelonae infection in an immunocompromised host in whom a primary source of the infection was identified.

Adult↗

Leukemia cutis. Analysis of 50 biopsy-proven cases with an emphasis on occurrence in myelodysplastic syndromes.

The hematologic, cytomorphologic, and cytogenetic features of 50 cases of leukemia cutis (LC), occurring in 40 patients, are presented. The patients' ages ranged from 19 to 75 years (mean, 42 years). The primary hematologic diagnoses in these patients included acute non-lymphoblastic leukemia (ANLL), 13 patients; myelodysplastic syndrome (MDS), 19 patients; chronic lymphocytic leukemia, 3 patients; chronic granulocytic leukemia, 3 patients; and polycythemia vera, 1 patient. Leukemia cutis developed in one patient without any known prior or subsequent hematologic disorder. The 13 cases of ANLL included French-American-British types M1 (1 case), M2 (5 cases), M3 (1 case), M4 (5 cases), and M5 (1 case). Leukemia cutis preceded blood and/or bone marrow manifestations of leukemia in nine patients with MDS and one with ANLL. The interval from skin biopsy to systemic leukemia ranged from 3 weeks to 20 months (mean, 6 months). In seven patients with MDS and three patients with ANLL, LC occurred concomitantly with leukemic transformation. Only two patients with MDS and LC did not have progression to acute leukemia during the 20 and 24 months they have been observed. Diagnoses other than LC initially were considered in five of the patients. LC was characterized most often by a dense mixed cellular dermal infiltrate that circumscribed vascular and adnexal structures. Nine patients with MDS (47%) and one with ANLL (8%) had complex chromosomal abnormalities in their bone marrow samples at the time of LC. This article reports the occurrence of LC in patients with MDS and suggests that LC is an early manifestation of leukemic transformation in these patients. These results may be important in identifying high-risk patients for early interventional therapy.

Adult↗

Atypical fibroxanthoma. Multiple immunohistologic profiles.

The clinical, histologic, and immunohistochemical features of 37 cases of atypical fibroxanthoma (AFX) are presented. Patients ranged in age from 13 to 95 years (mean, 69). Thirty AFXs occurred on the head and neck, and seven lesions developed on the trunk or extremities. The morphologic spectrum varied from a predominant spindle cell pattern with focal cellular pleomorphism to numerous bizarre epithelioid cells with multinucleated giant cells. The spindle cell component in these lesions ranged from 10 to 90% of the constituent cells. Most (31 of 37) AFXs also contained pleomorphic giant cells. Small numbers of S-100-positive dendritic cells were present in 11 cases. Five cases showed variable reactivity with anti-factor-XIIIa. Fifteen (41%) of the AFXs stained for muscle-specific actin or smooth muscle actin and 21 (57%) expressed CD68 (detected with monoclonal KP1), a monocyte-macrophage marker. Reactivity for these antigens was seen in all lesional cell types (spindled, epithelioid, and bizarre). Four immunologic profiles were observed: CD68 only (13 cases), actin only (7 cases), double positives (8 cases), and double negatives (9 cases). No significant differences in staining characteristics were observed in the head and neck versus the trunk and extremity lesions. These results expand the immunohistochemical spectrum of AFX, suggest the concept of heterogenous bimodal "fibrohistiocytic" and "myofibroblastic" phenotypes, and provide further evidence that an integrative, nonalgorithmic approach is necessary in the analysis of these and other spindle cell cutaneous lesions.

Actins↗

Alopecia universalis in an HIV-positive patient: possible insight into pathogenesis.

Alopecia universalis, a variant of alopecia areata, is a disease of unknown etiology, though evidence for an autoimmune etiology continues to mount. We report an HIV-positive patient with altered T-lymphocyte subsets in whom alopecia universalis developed. A skin biopsy of the patient's scalp demonstrated a classic perifollicular lymphocytic infiltrate, and immunophenotyping of the same specimen revealed that the majority of the cells were CD4+ lymphocytes. During the active loss of hair, the patient's CD4/CD8 ratio was decreased. This ratio normalized during the period of regrowth. Our data suggest that systemic immune dysfunction, as seen in HIV infection, may be more important in mediating alopecia areata than localized immune responses. Given the proposed mechanism of alopecia areata developing in this patient, i.e. influx of CD4+ lymphocytes to the perifollicular regions of skin when the CD4/CD8 ratio is low, it is surprising that alopecia areata is not seen more commonly in patients with HIV infection.

Adult↗

The spectrum of cutaneous disease in leukemias.

Cutaneous eruptions are frequent complications in the clinical course of patients with leukemia. Leukemia cutis is occasionally the cause of the eruption, but in many cases the lesions are nonleukemic. We have retrospectively selected all skin biopsies from patients with a computer-coded diagnosis of leukemia seen in the Stanford University Department of Pathology in the last 7 years, and separated these cases into the broad categories of acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and chronic lymphocytic leukemia (CLL). We also analyzed separately those cases seen in patients treated with bone marrow transplantation from those treated with standard chemotherapy regimens. We found that leukemia cutis was seen frequently as the cause of lesions in patients with CML and CLL. In contrast, a wide variety of lesions were seen in patients with AML, including a greater number of infectious lesions, drug reactions, vasculitis, and lesions secondary to a hemorrhagic diathesis. In the bone marrow transplantation patients, graft vs host disease was usually the cause of skin lesions in those transplanted for CML and ALL, but again those patients with an underlying diagnosis of AML showed a wide variety of lesions including drug reactions, fungal infections and leukemia cutis. Finally, 6% of cases from patients with AML showed intraepidermal blistering disorders of various types, an association that has not been previously reported.

Biopsy↗

Immunophenotypic analysis suggests that granuloma faciale is a gamma-interferon-mediated process.

Granuloma faciale (GF) is an uncommon inflammatory dermatosis with characteristic clinical and histologic features. Very little is known about its pathogenesis. We used a battery of immunoperoxidase lymphocyte markers to study the population of hematopoietic cells present in a case of GF. The majority of non-myelocytic hematopoietic cells present were T-helper lymphocytes. The cells stained strongly with antibodies against the interleukin-2 receptor and with anti-lymphocyte functional antigen (LFA 1 alpha) antibodies. Overlying keratinocytes did not stain with ICAM-1 or HLA-DR, which may account for the presence of the Grenz zone in granuloma faciale. These findings suggest that a gamma-interferon-mediated process may play some role in the pathogenesis of this disorder.

Adult↗

Dermal dendrocytes are decreased in collagenomas.

Dermal dendrocytes comprise a subset of spindle-shaped cells which normally reside in the dermis. While they appear to play some role in the reticuloendothelial system, their exact functions have not been completely elucidated. In addition to their purported immunologic functions, it has been suggested that dermal dendrocytes may play an inhibitory role in the regulation of dermal collagen synthesis. We examined 7 collagenomas with antibodies directed against factor XIIIa (FXIIIa) in order to test the hypothesis that dermal dendrocytes were focally diminished in these hamartomatous overgrowths of collagen. In all cases, there was a marked diminution in the number of FXIIIa-positive cells in the lesional dermis when compared to the surrounding dermis. Our data support the hypothesis that dermal dendrocytes may be involved in regulation of collagen synthesis.

Adolescent↗

Infantile (juvenile) capillary hemangioma: a tumor of heterogeneous cellular elements.

Infantile (juvenile) capillary hemangiomas are vascular neoplasms which can appear quite infiltrative histologically and are characterized by cords of cells with areas of marked cellularity. While vessels can be distinguished in most cases, there are many cells which do not appear to be endothelial in origin. We labeled 5 such cases with antibodies directed against factor VIII-related antigen, CD34, alpha actin, factor XIIIa and PC-10. Anti-factor VIII-related antigen labeled all endothelial cells and did not label cells away from vessels. Anti-CD34 recognized similar cells and also stained a subset of interstitial cells. Anti-alpha muscle defined pericytes and stained few interstitial cells and none of the endothelial cells. Many of the interstitial spindled and cuboidal cells stained strongly with anti-factor XIIIa. The majority of the mitotic activity was concentrated in the interstitial cells. These observations lend support to the concept that infantile (juvenile) capillary hemangioma is a tumor of primitive cells with capabilities for differentiating toward endothelial cells and pericytes. It is not clear whether a similar stem cell population gives rise to dermal dendrocytes, or whether these represent an immune response to the neoplasm.

Actins↗

Lymphocytes infiltrating primary cutaneous neoplasms selectively express the cutaneous lymphocyte-associated antigen (CLA).

The cutaneous lymphocyte-associated antigen (CLA) is the T-cell ligand for E-selectin and is involved in tissue selective migration of memory/effector T cells to chronic inflammatory sites in skin. Here, we examine the hypothesis that CLA is also involved in the local host immune response to cutaneous neoplasms. Eleven primary cutaneous melanomas, nine primary cutaneous squamous cell carcinomas, and 11 assorted neoplasms metastatic to cutaneous and noncutaneous sites were immunostained with anti-CLA (HECA-452), as well as antibodies directed against B cells (CD20), T/NK cells (CD43), and memory/effector T cells (CD45RO). Essentially all of the lymphocytes surrounding and infiltrating both the cutaneous and noncutaneous tumors were CD43+/CD20-, and most expressed the memory/effector marker CD45RO. CLA was expressed on 10 to 80% (mean: 50%) of T cells associated with primary cutaneous neoplasms (including both melanomas and squamous cell carcinomas) but was essentially absent from noncutaneous primaries (including those metastatic to dermis) and from cutaneous primaries metastatic to dermis or other sites. Overall, the results suggest that CLA+memory T cells are a major component of the local host immune response to cutaneous neoplasms and are likely recruited to the skin by site-specific rather than tumor-specific mechanisms. The lack of a CLA+T-cell response to dermal metastases suggests that epidermal involvement may be required to attract this subset.

Antigens, Differentiation, T-Lymphocyte↗

Desipramine-induced blue-gray photosensitive pigmentation.

BACKGROUND: Blue-gray pigmentation of the skin can be elicited by several medications. We report the first case (to our knowledge) of desipramine-induced photosensitive blue-gray pigmentation. OBSERVATIONS: Diffuse blue-gray pigmentation on sun-exposed surfaces was noted in a healthy 48-year-old woman who had been taking desipramine hydrochloride for 8 years. Ultrastructural studies demonstrated the presence of melanin and homogeneous electron-dense material in the dermis. CONCLUSIONS: We conclude that tricyclic antidepressant agents represent another class of medications responsible for blue-gray cutaneous pigmentation.

Desipramine↗

Paraneoplastic pemphigus with autoantibody deposition in bronchial epithelium after autologous bone marrow transplantation.

Paraneoplastic pemphigus is a newly described syndrome in which patients have a severe mucocutaneous eruption with clinical features reminiscent of both erythema multiforme major (Stevens-Johnson syndrome) and pemphigus vulgaris, in association with non-Hodgkin's lymphomas and other malignant neoplasms. These patients have autoantibodies that bind to a characteristic set of epidermal proteins: desmoplakin I and desmoplakin II (molecular weight equals 250 kd and 210 kd, respectively), both major cytoskeletal structural proteins associated with desmosome cellular junctions within all epithelia, the bullous pemphigoid antigen, a 230 kd protein associated with hemidesmosomes, and a 190,000-d protein that has not been characterized. In this report, we describe a patient with paraneoplastic pemphigus who had (1) non-Hodgkin's lymphoma in apparent complete remission following autologous bone marrow transplantation, (2) very tense blisters reminiscent of bullous pemphigoid, (3) a unique pattern of immune deposits within the skin, and (4) IgG deposits within the epithelium of the pulmonary bronchi associated with respiratory compromise.

Autoantibodies↗

Restrictive dermopathy. Report of two affected siblings and a review of the literature.

BACKGROUND: Restrictive dermopathy is a lethal genetic disorder consisting of abnormally tight skin, generalized joint contractures, distinctive facies, and pulmonary hypoplasia. Autosomal recessive inheritance has been suggested based on multiply affected siblings and some reports of parental consanguinity. This article describes two siblings with the restrictive dermopathy syndrome and reviews previously reported cases. OBSERVATIONS: Eight other cases have been reported in the literature as restrictive dermopathy. These cases have shared striking similarities in their clinical histories and phenotypes. The skin in these infants has been described as rigid and tense, with skin biopsy specimens showing a thick epidermis, thin dermis, abnormally arranged collagen bundles, and poorly developed appendages. Other prominent features are flexion contractures and craniofacial and pulmonary abnormalities. The genetic and/or developmental defects leading to the restrictive dermopathy syndrome are presently not known. CONCLUSIONS: The restrictive dermopathy syndrome is distinct and is easily differentiated from other congenital diseases such as the icthyoses and also from the clinical conditions of sclerema neonatorum and subcutaneous fat necrosis of the newborn. Recognition of this syndrome is important for determining the prognosis of affected infants and for recommending genetic counseling to affected families.

Contracture↗

Immunohistochemical examination of lichen nitidus suggests that it is not a localized papular variant of lichen planus.

BACKGROUND: Lichen nitidus is believed, by some, to be a variant of lichen planus, and by others to be a distinct entity. OBJECTIVE: We examined five cases of lichen nitidus with immunohistochemical reagents designed to characterize the dermal inflammatory infiltrate in an attempt to resolve the uncertainty. METHODS: We stained formalin-fixed, paraffin-embedded tissue sections with the following antibodies: L26, A6, KP1, BerH2, OPD4, and HECA-452. RESULTS: The inflammatory infiltrate was 90% A6+, with few L26+ cells. In contrast to lichen planus, KP1+ macrophages were seen and fewer of the lymphocytes demonstrated HECA-452. Fifty percent to 80% of lymphocytes were OPD4 positive, similar to that usually seen in lichen planus. Rare Ki-1+ cells were seen in one case. CONCLUSION: We believe that the pattern of a mixed cellular infiltrate characterized by macrophages and a helper T cell response with few HECA-452+ cells is somewhat different from the pattern seen in lichen planus, wherein almost all of the cells are CD4+/HECA-452+ lymphocytes. This suggests a different immunologic pathogenesis.

Dermatitis↗

Dysplastic nevi can be diagnosed and graded reproducibly: a longitudinal study.

BACKGROUND: Poor interobserver reproducibility in diagnosing and grading dysplastic melanocytic nevi is often cited as evidence against the ability of pathologists to recognize such an entity. OBJECTIVE: We attempted to examine the diagnostic profiles of melanocytic lesions of two dermatopathologists in a stable population base. METHODS: All 2600 melanocytic neoplasms were diagnosed at Stanford University Medical Center during the past 4 years by one dermatopathologist from 1987 to 1989 and a different dermatopathologist in 1990 and 1991. The two independently evaluated these lesions unaware of the other's criteria. RESULTS: The diagnostic profile of the two pathologists shows a striking degree of similarity: 76.7% versus 75.3% of all nevi were diagnosed as acquired melanocytic nevi, 8.8% versus 12.0% were diagnosed as mildly dysplastic, 7.0% versus 6.8% as moderately dysplastic, and 2.7% versus 1.6% as severely dysplastic. CONCLUSION: Our findings suggest that the two pathologists are using reproducible criteria for diagnosing and grading dysplastic nevi.

Dysplastic Nevus Syndrome↗

Differences in direct immunofluorescence staining patterns in epidermolysis bullosa acquisita and bullous pemphigoid.

BACKGROUND: Both bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA) are characterized by linear IgG deposits along the basement membrane zone (BMZ). Although these diseases can be distinguished by special tests, the staining pattern on direct immunofluorescence (DIF) is identical. OBJECTIVE: The purpose of the present study was to reevaluate DIF as a diagnostic tool in differentiating EBA from BP. METHODS: We performed DIF studies on biopsy specimens from eight consecutive patients with EBA and 18 consecutive patients with BP. RESULTS: In five of eight cases of EBA, C3 deposition was essentially absent. IgG was the predominant class of immunoglobulins in the deposits and was present along the BMZ in all eight cases. C3 was present in 17 of 18 cases of BP. IgG was the predominant immunoglobulin present in 15 of these 18. CONCLUSION: Patients with EBA are more likely to have linear IgG staining along the BMZ without concomitant C3 deposition than are patients with BP. This difference may be a function of the ability of the autoantibodies to fix complement.

Adult↗