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B R Smoller

Publications and source records attributed to B R Smoller.

At least 73 records · Page 4Linked to original sources

No role for human herpes virus 8 in the etiology of infantile capillary hemangioma.

Infantile capillary hemangiomas are vascular neoplasms that can appear quite infiltrative histologically and that are characterized by cords of cells with areas of marked cellularity. These lesions have been shown to contain a population of rapidly proliferative endothelial cells. Given the recent association between the presence of human herpes virus 8 (HHV8) and another proliferative vascular lesion, Kaposi's sarcoma, we used polymerase chain reaction technology to examine a series of 16 biopsy specimens from 15 infantile capillary hemangiomas for the presence of HHV8 DNA. We were unable to detect HHV8 DNA in any of the lesions studied. All of the cases were examined in parallel with a case of Kaposi's sarcoma that was known to be positive for HHV8 DNA and a series of negative controls. In all of our cases, amplification of beta-globin gene DNA demonstrated adequate preservation of DNA in the tissue studied. These findings suggest that not all endothelial cell proliferations can be attributed to HHV8 and that the etiology of some of these conditions remains unclear.

Capillaries↗

Trichoepithelioma with an adjacent basal cell carcinoma, transformation or collision?

Trichoepitheliomas (TEs) are benign follicular neoplasms that can be difficult to separate histologically from basal cell carcinomas (BCCs). It is important to make this distinction, because the treatments and prognoses differ for the two lesions. Previous reports have employed both histologic and immunohistochemical data in order to separate these two lesions. It is believed that transformation from a TE to a BCC is a rare event. We describe a case in which a single lesion with features of TE and BCC is present in a patient with multiple lesions of BCC.

Adult↗

Lack of the t(2;5) or other mutations resulting in expression of anaplastic lymphoma kinase catalytic domain in CD30+ primary cutaneous lymphoproliferative disorders and Hodgkin's disease.

The t(2;5) (p23;q35) chromosomal translocation has been found in a high proportion of lymph node-based CD30+ large cell lymphomas of T-cell lineage. This translocation is believed to result in the expression of a fusion protein containing the catalytic domain of anaplastic lymphoma kinase (ALK) under the control of the promoter for nucleophosmin, a nucleolar phosphoprotein. Expression of ALK activity, which does not normally occur in lymphocytes, is postulated to be involved in the pathogenesis of lymphomas bearing the t(2;5) translocation. Several primary cutaneous lymphoproliferative disorders and Hodgkin's disease are also known to contain CD30+ large lymphoid cells. To determine the role of the t(2;5) translocation in these diseases, we developed a DNA-based polymerase chain reaction (PCR)/Southern blot assay to detect this translocation at the genomic level in lymphomatoid papulosis (14 cases), primary cutaneous CD30+ large cell lymphoma of T-lineage (10 cases) and Hodgkin's disease (13 cases). Two cases of pityriasis lichenoides were also studied. The t(2;5) translocation was not present in any of these specimens. To determine if some other somatic mutation might have resulted in inappropriate expression of ALK catalytic domain, we devised an RNA-based reverse transcriptase-PCR assay to detect transcripts encoded by this ALK region. None were found in the six additional cases of lymphomatoid papulosis that were studied. In aggregate, these results strongly suggest that inappropriate expression of ALK is not involved in the pathogenesis of these CD30+ lymphoproliferative disorders, and that lymph node-based CD30+ large cell lymphoma is a disease that is biologically distinct from skin-based CD30+ lymphoproliferative disorders and Hodgkin's disease. Using methods developed for this report, we also cloned and sequenced the t(2;5) genomic junctional sequences present in the SUP-M2 and SU-DHL-1 cell lines. These intron sequences will be useful for mapping t(2;5) breakpoint clusters.

Adult↗

Immunohistochemistry in diagnostic dermatopathology.

Immunopathology continues to be important in diagnostic dermatopathology. Immunopathology is an invaluable tool for assessing the tissue of origin or direction of differentiation of cells. In some cases this can result in a more precise diagnosis. This article reviews the role of immunopathology in determining the biologic behavior of hematolymphoid infiltrates. It explores the methodology of immunoperoxidase, discusses the most commonly used antibody reagents, and presents a series of diagnostic dilemmas in which immunopathology can be useful. In each case a strategy is established that maximizes the likelihood of making a definitive diagnosis.

Antibodies↗

Increased proportion of aggressive-growth basal cell carcinoma in the Veterans Affairs population of Palo Alto, California.

BACKGROUND: We have noted a high frequency of aggressive-growth basal cell carcinomas (BCCS) in our patient population. Subtypes observed with increased frequency include morpheaform, infiltrative, and micronodular. OBJECTIVE: Our purpose was to examine the frequency of histologic subtypes of all BCCs seen in the dermatology clinics in the Veterans Affairs Palo Alto Health Care System in an 18-month period. METHODS: We reviewed 432 consecutive primary BCC biopsy specimens taken from 252 patients. RESULTS: Aggressive-growth BCC was observed in 20.7% of biopsy specimens, including 13.4% morpheaform, 5.7% infiltrative, and 1.6% micronodular subtypes. The mean age of the patient population was 70 years, with a standard deviation of 9.1 years. CONCLUSION: Our observed percentage of aggressive-growth BCC is substantially higher than in most other large studies. A high frequency of aggressive-growth BCC coupled with the increasing incidence of nonmelanoma skin cancer may have significant implications for future health care resource allocation.

Adult↗

Immunoperoxidase techniques in the evaluation of cutaneous lymphocytic infiltrates.

The widespread availability of immunoperoxidase technology and antibody probes over the past 15 years has changed the discipline of dermatopathology. In no aspect is this more evident than in the microscopic study of cutaneous lymphoid infiltrates. In the following review, the discussion focuses on some of the ways in which immunophenotyping is used to enhance the diagnosis of cutaneous lymphoproliferative disorders. A strategy for the use of immunophenotyping in some common clinical situations is forwarded. The immunopathologic findings can be helpful in resolving problems in the differential diagnosis of lymphoma and mimics of lymphoma.

Diagnosis, Differential↗

Gross cystic disease fluid protein-15 reactivity in extramammary Paget's disease with and without associated internal malignancy.

Extramammary Paget's disease (EMP) is a rare eczematoid disorder occurring mainly in apocrine-gland-bearing regions. Its histogenesis is controversial. Several investigators have proposed that EMP is a heterologous entity, with some cases representing a de novo adenocarcinoma in situ arising in the epidermis and others being epidermotropic metastases or a direct extension of an associated internal malignancy. We have studied 26 cases of EMP with and without associated internal malignancy for their reactivity with a monoclonal antibody directed at gross cystic disease fluid protein-15 (GCDFP-15). The diagnosis of EMP has been previously established for all cases using histochemical and immunohistochemical stains. Six of our 26 cases had a concomitant underlying carcinoma (one transitional cell carcinoma of the bladder, four adenocarcinomas of the rectum, one adenosquamous carcinoma. Only one of these six cases showed reactivity with GCDFP-15. In contrast, 16 of 20 cases of EMP without associated internal malignancy were strongly reactive with GCDFP-15 (> 5% of tumor cells). Variable GCDFP-15 reactivity in cases of EMP with and without associated internal malignancy supports the concept that EMP is a heterologous disorder. Positive GCDFP-15 in a patient with EMP may indicate a low probability of associated internal malignancy and may provide valuable clinical information.

Adenocarcinoma↗

Differential sensitivity of estrogen/progesterone receptors and BRST-2 markers in metastatic ductal and lobular breast carcinoma to the skin.

Cutaneous metastases arising from breast carcinoma are quite common. A standard panel of immunohistochemical markers including estrogen receptor (ER), progesterone receptor (PR), and BRST-2 are frequently used in surgical pathology to identify neoplasms with breast differentiation. It is well known that as the grade of a tumor increases, and as tumors lose their differentiation, immunohistochemistry results become more unpredictable in determining possible primary sites of origin. Although previous studies have identified a decrease of ER sensitivity in breast metastases, a possible sensitivity differential of cutaneous metastases of invasive lobular versus invasive ductal carcinoma by using the standard immunohistochemical panel has not been previously reported. With the standard panel, we compared the staining sensitivity of metastatic invasive ductal carcinoma (10 cases) to metastatic invasive lobular carcinoma (four cases) to the skin. ER positivity was identified in one case of metastatic ductal carcinoma and none of the four lobular carcinomas. PR positivity was noted in all cases of metastatic ductal and lobular carcinoma. BRST-2 positivity was found in only two of 10 cases of metastatic ductal carcinoma and all four of four cases of metastatic lobular carcinoma. These results indicate that a differential sensitivity exists for the BRST-2 marker when comparing cutaneous metastases of invasive lobular with invasive ductal carcinoma.

Aged↗

Proliferation and apoptosis within juvenile capillary hemangiomas.

Capillary hemangiomas (CH) are benign vascular neoplasms of childhood that undergo a natural course of postnatal growth followed by spontaneous involution and often complete regression. There are currently no established standards for the identification of the growth phase of CH. We retrospectively examined 24 CH specimens for staining with MIB1, a monoclonal antibody directed at the same proliferation-related antigen as Ki-67, and antibody to bcl-2, a protooncogene product associated with inhibition of cellular apoptosis, and correlated these findings with the growth phase. All lesions demonstrated more positively with MIB1 than with bcl-2, with more prominent staining in interstitial cells and an inverse correlation with increasing age. When calculations were adjusted for vascular lumina predominance, staining similarly decreased but at a later age. Our study supports interstitial cell-predominant proliferation within CH. In addition, bcl-2 expression was demonstrated, also interstitially predominant, and showed a decrease with aging, suggesting that programmed cellular death is involved in the growth regulation of these lesions and that regression is associated with changes in both proliferation and apoptosis. Last, both proliferation and bcl-2 expression showed a marked decrease later in more vascular channel-predominant lesions, possibly suggesting that such lesions undergo longer periods of growth before entering the involutional phase.

Adolescent↗

Evidence against a role for human T-cell lymphotrophic virus type I (HTLV-I) in the pathogenesis of American cutaneous T-cell lymphoma.

We used a standard polymerase chain reaction (PCR)/Southern blot assay (sensitivity > 10(-5)) to detect human T-cell lymphotrophic virus type I (HTLV-I) proviral pX, pol, and env genes in the lesional skin of 42 American patients with cutaneous T-cell lymphoma (CTCL). As in some prior reports using similar methods, a variable proportion of PCR tests were positive (seven of 42 for pX, three of 42 for pol, and two of 37 for env), resulting in an overall positive test rate of 12 of 121 (10%). To determine the significance of these positive test results, we performed several additional studies. D1S80 polymorphism analysis of CTCL cases and HTLV-I PCR analysis of non-CTCL dermatosis controls showed no evidence that positive PCR tests resulted from sample mislabeling, gross HTLV-I contamination, or human endogenous retroviruses. We then modified the standard PCR assay to incorporate ultraviolet (UV) light to destroy low-level PCR contamination. With this modified assay (sensitivity > 10(-5)), only three of 12 previously positive cases were still positive, suggesting that the earlier positives were due to trace contamination of PCR reagents or trace contamination of sample DNA. This interpretation was also supported by: (i) a match between pX and pol sequences cloned from one PCR-positive specimen and the MT4-positive control, (ii) our inability to confirm HTLV-I in any PCR-positive case using genomic dot blotting (sensitivity > 10(-2)), and (iii) negative PCR results when new samples from two of the remaining positive cases were analyzed. Finally, we used our modified UV/ PCR/Southern blot assay to test an additional 28 cases of American CTCL for pX. All of them were negative. Although these studies of 70 cases of American CTCL do not exclude the possibility that another virus is involved in the pathogenesis of this disease, they provide strong evidence against a role for HTLV-I. Furthermore, they emphasize the need for special strategies to control for false-positive PCR tests that can result from even trace levels of contamination with viral DNA. As a consequence, associations between diseases and viruses should be viewed skeptically if they are based primarily on conventional PCR data.

Base Sequence↗

Perivascular mast cells in urticaria pigmentosa.

We have quantified perivascular mast cells in cases of urticaria pigmentosa, urticaria, and dermal hypersensitivity reactions. To facilitate reproducibility, the mast cells were counted for a precisely defined vessel unit. These vessel units were divided arbitrarily into those < or = 55 microns and > 55 microns in largest diameters. Urticaria pigmentosa showed an average of 6.4 +/- 1.9 and 22.8 +/- 13.2 mast cells for vessel unit < or = 55 microns and > 55 microns, respectively. Urticaria yielded a lower number of mast cells: 1.5 +/- 0.2 and 2.9 +/- 0.9 for the same respective vessel units. Dermal hypersensitivity reactions revealed an average of 1.6 +/- 0.4 and 2.2 +/- 0.7 mast cells, and the normal skin showed 1.5 +/- 0.3 and 2.4 +/- 0.6 mast cells for each of the vessel units of < or = 55 microns and > 55 microns. The perivascular mast cell distributions of urticaria pigmentosa are statistically different from those of urticaria and dermal hypersensitivity reactions with p < 0.0001. No statistical difference was noted between urticaria, dermal hypersensitivity reactions, and normal skin. The percentages of vessel units < or = 55 microns with > or = 5 mast cells and vessel units > 55 microns with > or = 10 mast cells were determined for each case. The average percentage of vessel units for the former and latter in urticaria pigmentosa was 82.6% and 58.9%, respectively. Urticaria yielded 0% and 0.2%, respectively. None of vessel units in the dermal hypersensitivity reactions or normal skin contained more than 5 mast cells in vessel units < or = 55 microns and more than 10 mast cells in vessel units > 55 microns. Cases of urticaria pigmentosa can be distinguished from other cutaneous eruptions containing mast cells using a simple counting technique on Giemsa stained sections.

Adolescent↗

Skin.

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Biopsy↗

Reassessment of histologic parameters in the diagnosis of mycosis fungoides.

The histologic diagnosis of mycosis fungoides (MF) can be difficult to establish and is based on interpretation of numerous subtle changes, most of which may be present to some degree in many inflammatory and neoplastic cutaneous conditions. To reassess the diagnostic criteria for making a histologic diagnosis of MF, we retrospectively reviewed histologic sections from 64 patients with mycosis fungoides (MF+) and compared the findings with sections from 47 patients who were biopsied to exclude MF and were shown not to have the disease (MF-). Patients were selected as MF+ or MF- independent of histologic findings based on the clinical course with at least 3 years of follow-up and immunophenotyping results. Following patient selection, at least two observers reviewed each slide without knowledge of final diagnosis and graded the intensity of approximately 25 histologic parameters. On univariate analysis, the following parameters were significant at beyond the p = 0.01 level: Pautrier's abscesses, haloed lymphocytes, exocytosis, disproportionate epidermotropism, epidermal lymphocytes larger than dermal lymphocytes, hyperconvoluted intraepidermal lymphocytes, and lymphocytes aligned within the basal layer. Haloed lymphocytes proved to be the most robust discriminator of MF from non-MF on multivariate analysis. These findings show that whereas many previously described features do discriminate between MF and inflammatory mimics, others are much less specific. Furthermore, few cases demonstrate all histologic features; for example, Pautrier's microabscesses were seen in only 37.5% of our cases. We conclude that a combination of specific histologic parameters can be used to establish a microscopic diagnosis of MF without the necessity of confirmatory immunophenotyping in the vast majority of cases.

Abscess↗

Heterologous mesenchymal proliferation of the skin.

BACKGROUND: A benign cutaneous mesenchymal lesion with features of dermatofibroma, dermatomyofibroma, and lipoma is described. OBJECTIVE: An attempt is made to classify this previously undescribed entity. METHODS: Tissue sections were studied with routine hematoxylin and eosin and a battery of immunoreactants to ascertain the nature of the cells within the lesion. RESULTS: The lesion described has a unique histologic appearance, containing elements of mature adipose tissue, smooth muscle, and fibrous tissue. CONCLUSION: Our findings suggest that this tumor is a distinct entity that is not exactly like any previously described lesion and we have given it a descriptive name.

Adult↗