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Bruce R Smoller

Publications and source records attributed to Bruce R Smoller.

At least 19 recordsLinked to original sources
PubMed2006

Introduction to the 2005 long course.

Dermatopathology, as with other fields of pathology, has undergone major changes in the last 25 years. Our understanding of epidermally derived neoplasms becomes far more advanced with each passing year. Evidence for this progress is readily apparent upon reviewing textbooks of dermatopathology over time and in examining the course contents of the long-course presentations at the United States-Canadian Academy of Pathology annual meetings. What was once a simple discussion of melanocytic neoplasms (thought to be a variant of sarcoma) has become a reasonably complex analysis of the histologic, immunologic, and molecular aspects of melanocytic neoplasia. Similarly, our understanding of the development of cutaneous squamous cell carcinoma is greatly enhanced. The understanding of the molecular alterations that result in full transformation offers great insight into carcinogenesis. This introductory essay briefly traces this progression in setting the stage for the series of more detailed chapters about epidermal neoplasms that follow.

Dermatology↗
PubMed2006

Histologic criteria for diagnosing primary cutaneous malignant melanoma.

Malignant melanoma accounts for the largest number of deaths attributed to skin cancer. It also provides the most diagnostic challenges for the histopathologist. This article, attempts to describe the histologic features most closely associated with the various growth patterns of the most common subtypes of melanoma. While it has been shown repeatedly that histologic subtypes likely provide clinicians and patients with minimal to no prognostic information, it is useful to separate these entities in order to elucidate the varied histologic features seen within the class of tumors known as melanoma. The discussion centers around a checklist of changes seen at the microscope that are associated with this diagnosis. The goal of this chapter is to provide the reader with one perspective on the series of changes that are used in order to establish (or exclude) a diagnosis of melanoma. There is a comprehensive literature that critically evaluates histologic parameters associated with this collection of tumors and relates them to prognostic information, and no attempt will be made to correlate the histologic change with prognostic information. This will be discussed in another chapter in this volume. Similarly, more esoteric subtypes of melanoma are characterized by histologic features that differ from the common types of melanoma and will be addressed in another chapter.

Diagnosis, Differential↗
PubMed2006

Squamous cell carcinoma: from precursor lesions to high-risk variants.

Cutaneous squamous cell carcinoma is second only to basal cell carcinoma in its incidence within our population. It is among the most common types of neoplasm afflicting the human race. Most cases are related to exposure to sunlight. This initial portion of the chapter will focus upon the biologic progression that results in the ultimate development of fully formed squamous cell carcinoma. The latter portion will focus upon the histologic features of squamous cell carcinoma, which may be potential prognostic indicators. While pathologists currently provide clinicians with information about many histologic features that may affect the outcome for patients with melanoma, there is little impetus for similar behavior on the part of pathologists when diagnosing squamous cell carcinomas. This is largely due to the relatively low metastasis rate for these tumors compared with melanomas; however, it may be possible for pathologists to separate out those squamous cell carcinomas with a higher chance for recurrence and metastasis. This chapter will examine many of these histologic features and propose a rationale for including this information in pathology reports.

Carcinoma, Squamous Cell↗
PubMed2006

Colchicine intoxication diagnosed in a skin biopsy: a case report.

Colchicine toxicity is a rare, but well-described clinical entity. The histopathologic findings in various organ systems have been delineated in colchicine intoxication; however, skin findings have only been described in rare cases. We present a case of colchicine toxicity diagnosed on skin biopsy in a patient presenting with mental status changes. Her cutaneous manifestation consisted of a diffuse, blanchable, violaceous, morbilliform rash involving the trunk and proximal extremities. The histopathologic findings included metaphase-arrested keratinocytes with underlying basal vacuolization. These features, considered in the setting of multiorgan dysfunction and a known exposure of colchicine, led to the diagnosis.

Biopsy↗
PubMed2006

Fli-1 expression in mycosis fungoides.

BACKGROUND: The Fli-1 transcription factor functions in cellular proliferation and tumorigenesis. Its role in various neoplasms and its presence in lymphocytes suggest a link between Fli-1 dysregulation and the pathogenesis of mycosis fungoides (MF). In this study, we further elucidate this possible link. METHODS: Sections from archived specimens were stained using a polyclonal antibody against Fli-1. The percentage of nuclei showing Fli-1 expression was recorded. These were compared with reactive dermatoses. RESULTS: All of the tumor stage lesions showed high levels of nuclear Fli-1 expression. Of plaque stage lesions, six of 12 (50%) showed the same intensity, while the remaining six of 12 varied significantly in their Fli-1 expression. The few patch stage lesions also showed varied expression. CONCLUSION: This study shows diffuse nuclear expression of Fli-1 in all tumor stage MF, whereas expression of this transcription factor varied widely in the early, epidermotropic stages. Although the numbers are too small to draw statistical significance, this study demonstrates an association between increased expression of Fli-1 and progression to tumor stage MF that merits further investigation. Additionally, the mixed expression of Fli-1 in the epidermotropic stages suggests that the role of Fli-1 in MF is related to neoplasia and not epidermotropism.

Biomarkers, Tumor↗
PubMed2005

Necrolytic acral erythema: a cutaneous sign of hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) infection is globally epidemic. Several mucocutaneous diseases are well established in association with HCV infection. Few case reports describe the recently recognized HCV-related skin disorder termed necrolytic acral erythema (NAE). METHODS: Thirty patients with NAE were identified in a university-based dermatology clinic in Cairo, Egypt. These patients were observed over time to document the clinical and histologic findings of this disorder. RESULTS: All patients were infected with HCV. Erythematous papules arose most commonly on the dorsal aspect of the feet, particularly the dorsal surface of the great toe. Progression resulted in confluence into erythematous dusky plaques with adherent scale and central erosion. The eruption extended to involve the lower leg and other regions in some patients but never affected palms or soles, the nail bed, nail plate, or mucous membranes. Skin biopsy specimens from fully evolved lesions displayed psoriasiform changes in association with more characteristic findings of keratinocyte necrosis and papillomatosis. LIMITATIONS: We did not perform a prospective review of patients known to be infected with HCV. Patients were identified from a general clinic population and then assayed for HCV serology. CONCLUSIONS: NAE is a distinctive skin disorder associated with HCV infection in all cases reported to date. Recognition of this disease should alert practitioners to the need for viral testing and appropriate counseling of patients.

Adolescent↗
PubMed2005

Exogenous trauma simulating perifollicular fibromas.

The patient is a 63-year-old woman who presented to her dermatologist for the removal of two nevi near her mouth. Histologic examination revealed melanocytic nevi showing maturation with dermal descent. Within the dermis, adjacent to these nevoid cells, were multiple large hair follicles that were surrounded by dense fibrosis. The fibrous sheaths contained thickened, dense collagen bundles and were well circumscribed, resembling perifollicular fibromas. Further discussion with the patient and the dermatologist revealed that the patient had "plucked" hair from these nevi. We, therefore, believe that the perifollicular fibrosis that we observed is secondary to trauma. We present this case to remind all that post-traumatic events can simulate perifollicular fibromas and that the erroneous diagnosis of such could lead to the erroneous diagnosis of Birt-Hoggs Dubé syndrome.

Diagnosis, Differential↗
PubMed2005

Mycobacteria other than Mycobacterium tuberculosis are not present in erythema induratum/nodular vasculitis: a case series and literature review of the clinical and histologic findings.

Erythema induratum (EI)/nodular vasculitis (NV) is characterized by recurrent crops of tender oedematous nodules on the lower legs. A lobular panniculitis with granulomatous inflammation, vasculitis, focal necrosis and septal fibrosis is present. Mycobacterium tuberculosis DNA has been detected in some lesions by means of polymerase chain reaction (PCR). Ten cases of EI/NV were found. H&E slides were reviewed. PCR assays for M. tuberculosis and mycobacteria other than M. tuberculosis (MOTT) were performed. PCR did not reveal M. tuberculosis (0%) or MOTT (0%) DNA, with positive controls, indicating the reliability of the assays. Among the MOTT, cutaneous infections are most commonly caused by M. marinum. Subcutaneous tuberculoid granulomas may be seen with M. kansasii, M. marinum, M. scrofulaceum and M. avium complex. M. gordonae, M. szulgai and M. malmoense rarely cause cutaneous infections. M. simiae, M. gastri and M. asiaticum are probably not cutaneous pathogens. M. tuberculosis and MOTT DNA was not found in EI/NV. EI/NV has diverse aetiologies with varying pathogeneses leading to similar histologic changes. The cases analysed may not have had an infectious aetiology. However, in EI/NV, performance of PCR for MOTT as well as M. tuberculosis complex may still be beneficial, particularly in cases from immunocompromised hosts.

Adolescent↗
PubMed2005

Unusual histological variants of cutaneous malignant melanoma with some clinical and possible prognostic correlations.

Malignant melanoma is known for the wide range of histological patterns it can assume mimicking other malignant tumors. We present a review of most of the unusual histological variants of cutaneous melanoma and describe their immunohistochemical features, associate clinical findings, and possible behavior related to the histological subtype. In addition, we propose their classification into four groups corresponding to the (1) architectural patterns; (2) cytologic features; (3) stromal changes; and (4) the possible association of these findings (i.e. architectural + cytologic features). Although most of these unusual variants have the same prognosis as conventional melanomas, with Breslow thickness and ulceration, being the most important predictor of survival in clinical stage I, some of them have a peculiar biologic behavior that the clinicians and the dermatopathologists should know in order to give melanoma patients all educational information available.

Humans↗
PubMed2004

Her-2 expression in cutaneous eccrine and apocrine neoplasms.

Cutaneous eccrine and apocrine glands have many histologic and immunologic similarities to ducts and acini of the breast. Thus, differentiating a primary cutaneous process from a metastatic breast carcinoma can be nearly impossible. In all, 10-34% of breast carcinomas overexpress HER-2 protein, a membrane-associated protein that functions in cell differentiation, adhesion and motility. As expression of this gene in cutaneous neoplasms has not been well characterized, we sought to determine HER-2 expression in a sample of benign and malignant cutaneous eccrine and apocrine neoplasms and to determine if there is value in using this protein expression in differentiating primary cutaneous from metastatic breast lesions. Totally, 85 primary cutaneous neoplasms and 11 cutaneous metastases from HER-2-positive breast carcinomas were retrieved from archived material at our institute. All cases were evaluated for HER-2 protein expression using the Dako Hercept Test kit. Membranous HER-2 staining was noted in three of the 85 cutaneous adnexal neoplasms: one hidrocystoma and two nodular hidradenomas. Seven of the 11 cutaneous metastases from HER-2-positive breast carcinomas maintained moderate-to-strong HER-2 expression. In conclusion, while 10-34% of breast carcinomas overexpress the HER-2 protein, only 3.5% of cutaneous apocrine and eccrine neoplasms in this study stained with the HER-2 antibody. These HER-2-positive cutaneous neoplasms typically do not pose a diagnostic dilemma in the setting of differentiation from breast metastasis. Additionally, although histologically these breast and cutaneous lesions may have morphologic similarities, the relative lack of HER-2 overexpression suggests that they are different nosologically. Finally, this study suggests that HER-2 protein expression can be a useful tool in differentiating a primary cutaneous appendageal neoplasm from HER-2 expressing metastatic breast carcinoma.

Adenoma, Sweat Gland↗
PubMed2004

Metalloproteinase-2 expression correlates with aggressiveness of cutaneous squamous cell carcinomas.

Matrix metalloproteinases compose a family of enzymes involved in degradation of the extracellular matrix. Tumor cells must penetrate the basement membrane and traverse the extracellular matrix in order to invade surrounding structures and metastasize to distant sites. Gelatinases, particularly gelatinase A (matrix metalloproteinase-2), demonstrate degradative activity against components of the basement membrane and may be involved in the progression of in situ squamous cell carcinoma lesions. Matrix metalloproteinase-2 overexpression has been correlated with tumor invasiveness and metastasis in a wide variety of cancer types, including squamous cell carcinoma arising on mucous membranes. However, correlation between matrix metalloproteinase-2 overexpression and the spread and prognosis of cutaneous squamous cell carcinoma has not been characterized in the literature at present. In this study, we used immunohistochemical techniques to examine the expression of matrix metalloproteinase-2 in 10 actinic keratosis, 15 in situ, 13 invasive, 13 primary (with documented metastatic disease), 11 metastatic, and 8 recurrent squamous cell carcinoma cases. We found that while the average staining intensity (scale 0-3+, 3+ being strongest) of actinic keratosis and in situ lesions was not statistically significant (0.87-1.3 and 0.75-1.4, respectively), the average staining intensity of invasive squamous cell carcinomas (1.6-2.5) was significantly greater than that of actinic keratosis and in situ lesions. Likewise, while the average staining intensity of primary squamous cell carcinomas and metastatic squamous cell carcinomas was not found to be statistically significant (3.1-3.5 and 3.1-3.8, respectively), the average staining intensity of these lesions was significantly higher than that of invasive lesions. We also found that the intensity of matrix metalloproteinase-2 staining correlates with cellular atypia, inflammation, neovascularization, and the invasive tumor front, as well as tumor aggressiveness, and may play a role in the pathogenesis, invasion, and metastasis of cutaneous squamous cell carcinoma.

Carcinoma, Squamous Cell↗
PubMed2004

Ets-1 immunohistochemical expression in non-melanoma skin carcinoma.

BACKGROUND: Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in non-melanoma skin carcinomas. DESIGN: A series of 26 primary cutaneous skin lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle Upon Tyne, England, UK) was scored by an average of the mean labeling intensity (MLI), where no nuclear staining = 0, weak nuclear staining = 1, moderate nuclear staining = 2, and strong nuclear staining = 3. RESULTS: All basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC) cases exhibited negative nuclear staining, for an average MLI of 0. Keratoacanthomas, squamous cell carcinoma in situ (SIS), and well-differentiated squamous cell carcinomas (SCCs) exhibited negative to weak nuclear staining, for an average MLI of 0.4 +/- 0.3. Moderately differentiated SCCs exhibited moderate nuclear staining, for an average MLI of 1.8 +/- 0.6. Poorly differentiated SCCs and metastatic SCCs exhibited very strong nuclear staining, with an average MLI of 2.8 +/- 0.2. CONCLUSIONS: Ets-1 is not expressed in cutaneous BCC or MCC and is weakly expressed in SIS and forms of well-differentiated SCC. Although the intensity of Ets-1 immunostaining distinguished between well-differentiated and poorly differentiated SCC (p < 0.0001), it failed to discriminate between in situ and well-differentiated SCCs. The preliminary data suggests Ets-1 may be important in the pathogenesis of invasive SCC.

Biomarkers, Tumor↗
PubMed2004

Histiocytic subpopulations in the gastrointestinal tract: distribution and possible relationship to function.

The distribution of specific histiocyte subsets within the human gastrointestinal tract has not been extensively characterized. Our goal was to immunohistochemically evaluate the distribution and location of CD1a-positive, CD68-positive, and Factor XIIIa (FXIIIa)-positive histiocyte subsets within the normal gastrointestinal tract and attempt to relate distribution to possible function. Twenty-nine samples of normal esophagus, stomach, small bowel, large bowel, and anus were routinely processed and immunohistochemically stained with antibodies to CD68, CD1a, and FXIIIa. The distribution and histologic location of histiocyte subsets were qualitatively analyzed. CD1a-positive cells were seen exclusively within anal and esophageal squamous mucosa. CD68 positive histiocytes were present in lamina propria and submucosa throughout the gastrointestinal tract and in Peyer patches. FXIIIa-positive histiocytes were also abundant in lamina propria and submucosa throughout the gastrointestinal tract, particularly around pericryptal sheaths and in parafollicular regions surrounding Peyer patches. Our results showed that there are distinct subpopulations of gastrointestinal histiocytes, and that distribution varies according to both cell type and site. Because Langerhans cells are epidermal antigen processing/presentation cells, their exclusive presence in squamous mucosa suggests an analogous function there. The prominence of both CD68 and FXIIIa-positive cells surrounding glandular pericryptal sheaths suggests that they are important to immune function at this mucosal interface and may play a role in communication between glands and lamina propria. In addition, the presence of specific histiocyte subsets within Peyer patches and para-follicular regions suggests that they are involved in different aspects of antigen processing associated with gut lymphoid tissue. Further studies are needed to explore the relation between specific histiocyte subsets and gastrointestinal disease processes.

Antigens, CD↗
PubMed2004

Merkel cell carcinoma: a clinicopathologic study with prognostic implications.

BACKGROUND: Merkel cell carcinoma (MCC) is a frequently aggressive neuroendocrine malignancy of the skin that presents in sun-exposed areas on elderly patients. Although originally described over 30 years ago, many aspects of MCC remain to be defined. Of particular importance is the need to identify prognostic factors capable of predicting the biological behavior of these tumors. Knowledge of these factors may help in determining which patients require more aggressive treatment regimens. In this study, we examined 25 cases of MCC with an attempt to identify clinical, histopathological, or immunohistochemical features capable of predicting disease outcome. METHODS: Features that we evaluated in each case included age, gender, race, tumor location, tumor size, depth of invasion, growth pattern, lymphocytic infiltration, mitotic activity, ulceration, necrosis, vascular invasion, and perineural invasion. In addition, we examined neural cell adhesion molecule and cytokeratin-20 expression using immunohistochemical methods. RESULTS: We found that most patients were males (84%) with an average age of 74 years. The tumors were located on the head and neck (68%) and upper extremities (32%). Overall, 64% of the patients developed metastatic disease to regional lymph nodes or distant sites (average follow-up time of 21 months). Local recurrence was also common, occurring in 29% of the patients. The overall 1- and 2-year survival rates were 80 and 53%, respectively. Histopathological examination revealed tumors with an average size of 7.2 mm. Common features included invasion into the subcutaneous adipose tissue, solid growth pattern, tumor necrosis, and vascular and perineural invasion. Findings that had a statistically significant correlation with poor outcome included tumor size > or =5 mm (p = 0.047), invasion into the subcutaneous adipose tissue (p = 0.005), diffuse growth pattern (p = 0.040), and heavy lymphocytic infiltration (p = 0.017). The remaining findings, including the immunohistochemical results, did not correlate with disease outcome. Using logistic regression models, we show that depth of invasion and degree of lymphocytic infiltration are strong predictors of disease outcome. CONCLUSIONS: The current controversies regarding the treatment of early-stage MCC (i.e., localized disease) underscore the importance of identifying clinicopathological features capable of predicting tumor behavior. In this study, we have identified several prognostic features in MCC. Perhaps, these features may prove useful in identifying patients who require more aggressive treatment regimens.

Aged↗
PubMed2004

Evaluation of anti-thrombomodulin antibody as a tumor marker for vascular neoplasms.

BACKGROUND: Various endothelial markers are available for the evaluation of vascular tumors and malformations, including anti CD34, anti-CD31, von Willebrand factor (vWF), and anti-thrombomodulin (anti-TM) antibodies. All have their limitations, and we sought to compare the utility of anti-TM antibody as a marker for several types of vascular neoplasms vs. previously established endothelial markers. METHODS: We examined immunostaining profiles of 30 capillary hemangiomas, 10 pyogenic granulomas, five tufted angiomas, 17 Kaposi's sarcomas, and nine angiosarcomas. Immunostains for TM, CD34, and vWF were carried out using a labeled streptavidin-biotin peroxidase detection system. RESULTS: Anti-TM antibody showed moderately intense immunostaining in 89% of benign and malignant vascular neoplasms. Anti-CD34 antibody showed moderate to diffuse immunostaining in 98% of vascular neoplasms, and vWF showed weak focal staining in 84% of all vascular neoplasms examined. CONCLUSION: Anti-TM antibody proved to be a sensitive marker for both benign and malignant vascular neoplasms. While not as sensitive as anti-CD34, it may have some advantages in specificity that would make it a more reliable vascular tumor marker in certain situations.

Antigens, CD34↗
PubMed2004

Detection of clonality with kappa and lambda immunohistochemical analysis in cutaneous plasmacytomas.

CONTEXT: Cutaneous plasmacytomas rarely occur in the setting of multiple myeloma. However, since poorly differentiated lesions may resemble other neoplasms, such as carcinoma, melanoma, and lymphoma, the diagnosis of cutaneous plasmacytoma may be difficult. OBJECTIVE: To demonstrate clonality using kappa and lambda immunohistochemical analysis in cutaneous plasmacytomas and to ascertain whether or not interpretation is hindered by background staining. DESIGN: Pathology reports of all patients with the diagnosis of multiple myeloma were reviewed. Twelve patients had cutaneous lesions diagnosed as plasmacytoma, and these lesions were analyzed for light chain restriction with kappa and lambda immunohistochemical analysis. RESULTS: In most cases (11 of 12), monoclonality was demonstrated. In the remaining case, monoclonality could not be established because most cells did not stain for either kappa or lambda. CONCLUSIONS: Light chain restriction can be demonstrated in most multiple myeloma-related cutaneous plasmacytomas, establishing the neoplastic nature of the infiltrate.

Clone Cells↗