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Biomedical subjects

Michael B Morgan

Publications and source records attributed to Michael B Morgan.

At least 19 recordsLinked to original sources

Acral keratosis with eosinophilic dermal deposits: a distinctive clinicopatholgic entity or colloid milium redux?

AIMS: The differential diagnosis of acral keratoses is broad. Encompassing a variety of infectious, heritable and degenerative disorders, emphasis upon the clinical setting and histologic subtlety are often required to arrive at the correct diagnosis. Herein, we report on a series of adult patients who presented with agminated or solitary papules of the distal finger found on histologic examination to contain amorphous eosinophilic deposits. RESULTS: The eosinophilic deposits were found in close proximity to the overlying epithelium and devoid of apoptotic keratinocytes, plasma cells, or vascular thickening reminiscent of amyloidosis or hyalinosis cutis. Special and immunostains yielded eosinophilic material that was elastin and Protein P negative. Despite a similar histomorphologic appearance to colloid milium, typical clinical features of this entity were not present. CONCLUSION: The etiologic significance of this condition is unknown. Potential sources of the material and a discussion of the differential diagnosis follow.

Aged↗

Human umbilical cord blood progenitor cells are attracted to infarcted myocardium and significantly reduce myocardial infarction size.

We are investigating the effects of human umbilical cord blood mononuclear progenitor cells (HUCBC) for the treatment of acute myocardial infarction because human cord blood is a readily available and an abundant source of primitive cells that may be beneficial in myocardial repair. However, there is currently no scientific consensus on precisely when to inject stem/progenitor cells for the optimal treatment of acute myocardial infarction. We used an in vitro assay to determine the attraction of infarcted rat myocardium at 1, 2, 2.5, 3, 6, 12, 24, 48, and 96 h after left anterior descending coronary artery (LAD) occlusion from 45 rats for HUCBC in order to determine the optimal time to transplant HUCBC after myocardial infarction. Our assay is based on the migration of fluorescent DAPI-labeled HUCBC from wells in an upper chamber of a modified Boyden apparatus through a semiporous polycarbonate membrane into wells in a lower chamber that contain either normal or infarcted myocardium. DAPI-labeled HUCBC (100,000) were placed in each of the separate wells above the membrane that corresponded to normal or infarct homogenate in the lower wells. The greatest HUCBC migration to infarcted myocardium occurred at 2 h and 24 h after LAD occlusion in comparison with normal controls. A total of 76,331 +/- 3384 HUCBC migrated to infarcted myocardium at 2 h and 69,911 +/- 2732 at 24 h after LAD occlusion (both p < 0.001) and significantly exceeded HUCBC migration to normal heart homogenate. The HUCBC migration remained greatest at 2 and 24 h after LAD occlusion when the number of migrated cells was adjusted for the size of each myocardial infarction. Injection of 106 HUCBC in saline into infarcted myocardium of non immunosuppressed rats within 2 h (n=10) or at 24 h (n=5) after LAD occlusion resulted in infarction sizes 1 month later of 6.4 +/- 0.01% and 8.4 +/- 0.02% of the total left ventricular muscle area, respectively, in comparison with infarction sizes of 24.5 +/- 0.02% (n=10) in infarcted rat hearts treated with only saline (p < 0.005). Acute myocardial infarction in rats treated with only saline increased the myocardial concentration of tumor necrosis factor-alpha (TNF-alpha) from 6.9 +/- 0.8% to 51.3 +/- 4.6%, monocyte/macrophage chemoattractant protein (MCP-1) from 10.5 +/- 1.1% to 39.2 +/- 2.0%, monocyte inflammatory protein (MIP) from 10.6 +/- 1.6% to 23.1 +/- 1.5%, and interferon-gamma (INF-gamma) from 8.9 +/- 0.3% to 25.0 +/- 1.7% between 2 and 12 h after coronary occlusion in comparison with known controls (all p < 0.001). In contrast, the myocardial concentrations of these cytokines in rat hearts treated with HUCBC did not significantly change from the controls at 2, 6, 12, and 24 h after coronary occlusion. The present investigations suggest that infarcted myocardium significantly attracts HUCBC, that HUCBC can substantially reduce myocardial infarction size, and that HUCBC can limit the expression of TNF-alpha, MCP-1, MIP, and INF-gamma in acutely infarcted myocardium.

Animals↗

Profiling differential gene expression of corals along a transect of waters adjacent to the Bermuda municipal dump.

A coral cDNA array containing 32 genes was used to examine the gene expression profiles of coral populations located at four sites that varied with distance from a semi-submerged municipal dump in Castle Harbour, Bermuda (previously identified as a point source of anthropogenic stressors). Genes on the array represent transcripts induced under controlled laboratory conditions to a variety of stressors both natural (temperature, sediment, salinity, darkness) and xenobiotic (heavy metals, pesticides, PAH) in origin. The gene expression profiles produced revealed information about the types of stressors. Consistent with other studies undertaken in Castle Harbour, the coral cDNA array detected responses to heavy metals, sedimentation, as well as oxidative stress.

Animals↗

Development of a coral cDNA array to examine gene expression profiles in Montastraea faveolata exposed to environmental stress.

The development of a cDNA array of coral genes and its application to investigate changes in coral gene expression associated with stressful conditions is described. The array includes both well-characterized and previously unidentified coral genes from Acropora cervicornis and Montastraea faveolata. Corals were exposed to either natural or anthropogenic stressors to elicit the expression of stress genes for isolation and incorporation onto the array. A total of 32 genes involved in protein synthesis, apoptosis, cell signaling, metabolism, cellular defense and inflammation were included on the array. Labeled cDNA from coral (Montastraea faveolata) exposed to elevated seawater temperature, salinity and ultraviolet light was tested against the microarray to determine patterns of gene expression associated with each stressor. Carbonic anhydrase, thioredoxin, a urokinase plasminogen activator receptor (uPAR) and three ribosomal genes demonstrated differential expression across all replicates on the array and between replicate colonies. Specific gene expression patterns produced in response to different stressors demonstrate the potential for gene expression profiling in characterizing the coral stress response.

Animals↗

Sternal erythema: a distinctive postsurgical eruption.

BACKGROUND/OBJECTIVE: Wound complications constitute a diverse array of surgical and dermatologic entities. We sought to describe the clinical and pathologic attributes of a series of patients in whom a distinctive thoracic surgical wound eruption developed after coronary bypass grafting. METHODS: We performed a detailed chart review, including history, surgical procedure notes, and biopsy findings, obtained from 3 patients; we examined the data and reconciled them with conventional etiologies in an attempt to discern a shared diagnosis and pathogenesis. RESULTS: The patients were white men (59, 68, and 73 years of age) in whom roughly symmetrical asymptomatic erythema developed within the borders of their sternal thoracotomy wounds between 1 and 2 years after open heart surgery. The cutaneous findings consisted of macular erythema and poikiloderma that blanched with external pressure. Biopsy findings yielded epithelial atrophy with capillary telangiectases. CONCLUSION: Although cellulitis, dermal hypersensitivity to surgically implanted hardware including sternal wire, and an anatomic variant of costal fringe remain as possible diagnoses, an additional consideration includes a form of postsurgical reflex sympathetic dystrophy.

Aged↗

A baffling basaloid blain.

Cutaneous metastases may present in a variety of histologic guises simulating more common primary tumors. We present the clinicopathologic features of a case masquerading as basal cell carcinoma. Epidermotropism, vascular invasion, and the absence of stromal retraction around tumor nests prompted further investigation. Clinical history and directed immunohistochemical staining ultimately revealed the diagnosis of cutaneous metastasis of transitional cell bladder carcinoma (TCC).

Aged↗

Verrucous psoriasis: a distinctive clinicopathologic variant of psoriasis.

Psoriasis is capable of presenting in a variety of clinical and pathologic guises including a rarely described variant variably termed hypertrophic or verrucous psoriasis. Herein, we describe the clinical and pathologic attributes of a large series of patients with this unusual variant of psoriasis and distinguish it from other entities in the differential diagnosis. The histopathologic features and clinical and demographic attributes of a series of 12 cases from 12 patients were reviewed by a single dermatopathologist (MM). The 12 patients consisted of 7 males and 5 females with an average age of 61.8 years (males 38-93 years, females 41-71 years). Eight of the patients were Caucasian, 3 Hispanic and 1 African-American. Six of the lesions were located on the knees, 4 involved the elbows, and 2 were seen on the dorsum of the hands (metacarpal-phalangeal joint). The clinical appearance of the lesions consisted of flesh-toned to white mammillated plaques (8 cases) and coalesced papules (4 cases). Each of the biopsies showed regular psoriasiform epidermal hyperplasia with acanthosis, hyperkeratosis, and either spongiform neutrophilic or Munro micro-abscesses. In addition, each showed papillomatosis with bowing of the peripheral rete ridges toward the center of the lesion (buttressing). At high power, epidermal neutrophils were seen in particular surmounting the tips of the suprapapillary plates with accompanying serum. Hypergranulosis and koilocytic change were not observed in any of the lesions. Human papilloma virus (HPV) immunostaining and periodic acid Schiff (PAS) special staining for fungi were negative. Verrucous psoriasis is a distinctive variant of psoriasis with overlapping clinical and pathologic features that might prompt consideration of verruca vulgaris. The presence of epidermal papillomatosis and epidermal buttressing seen in these lesions is reminiscent of the histologic features of verruca vulgaris. Similarly, the presence of coalesced papules might prompt clinical consideration of verruca vulgaris as well. It is likely that this under recognized clinicopathologic entity represents a patterned response of the epithelium to repeated trauma/irritation typical of the anatomic locations that were encountered in this series. Recognition of this entity should preempt confusion with verruca vulgaris or other entities capable of producing wart-like epidermal changes.

Adult↗

Immunohistochemical expression of Bax and Bcl-2 in penile carcinoma.

There is a complex interplay between the pro-apoptotic Bax and anti-apoptotic Bcl-2 family of proteins and the tumor suppressor gene p53. The pathogenic role of Bax and Bcl-2 protein expression in penile carcinomas has not previously been investigated. We examined Bax and Bcl-2 expression in verrucous (VC) and squamous cell carcinoma (SCC) of the penis. Herein we also present a concise review of p53, Bcl-2/Bax ratios, and their relationship to apoptosis. Fourteen cases of penile carcinoma, including 7 VC and 7 well-differentiated SCC, were analyzed for Bax and Bcl-2 expression by immunohistochemical analysis of paraffin embedded archived tissues. The number of positively staining tumor cells was enumerated per 100 tumor cells within non-overlapping high power fields. The Bax immunoreactivity was similar in VC (19+/-3%) and well-differentiated SCC (15+/-4%) (p = 0.69). The expression of Bcl-2 protein was significantly higher in well-differentiated SCC (69+/-12%) compared to VC (36+/-14%) (p = 0.04). The mean Bcl-2/Bax ratio was significantly lower in VC (1.89) compared to well-differentiated SCC (4.6) (p = 0.05). These findings indicate that penile VC and SCC are immunophenotypically distinct. Bax expression is comparable in verrucous and low-grade squamous cell carcinomas, but Bcl-2 expression of Bcl-2 is significantly higher in the squamous cell carcinomas.

Carcinoma, Squamous Cell↗

Cutaneous angiosarcoma: a case series with prognostic correlation.

BACKGROUND: Cutaneous angiosarcoma (CA) is a rare and aggressive endothelial-derived sarcoma. Few large studies have examined the clinicopathologic and prognostic attributes of CA. OBJECTIVES: We sought to discern the potential prognostic significance of a variety of demographic features (i.e., age, sex, location), histologic attributes (i.e., depth of invasion, tumor necrosis, tumor cell morphology, margin status, mitoses), and follow-up data (i.e., tumor recurrence, metastases) in CA. METHODS: The statistical influence of age, sex, anatomic location, tumor depth of invasion, tumor cell morphology, presence or absence of necrosis, number of mitoses, and margin status on time to tumor recurrence and metastases were examined in a series of 47 patients with CA. Angiosarcoma arising within the breast, in a previously irradiated anatomic site, and a pre-existing vascular malformation or one associated with a lymphedematous extremity were excluded from study. RESULTS: Most of the patients were men (76%), with an average age of 75.1 years (range: 59-92 years). The most common location was the head and neck region (96%). The most common presentation was of a rapidly expanding erythematous patch, and the most common clinical impression was angiosarcoma. The average external diameter of the tumor was 5.3 cm (range: 1.1-8.9 cm). The most common histologic pattern was characterized by anastomosing dissecting sinusoids lined by atypical endothelial cells (64%) with 15% of cases showing a diffuse epithelioid or spindle cell proliferation and 21% showing a mixture of the 2 histologic patterns. The average depth of tumor invasion was 2.86 mm (range: 1.8->6.0 mm). Of the tumors, 78% had a mitotic rate that exceeded 3/mm(2). Follow-up was available in 37 of the patients and ranged from 6 to 65 months. The 5-year local recurrence rate was 84% and the overall 5-year survival was 34%. Most patients died as a result of their disease with widespread pulmonary, cardiac, and/or brain metastases. CONCLUSIONS: Of the gross and histologic features, external diameter (>5 cm), depth of invasion (>3 mm), mitotic rate (>3 HPF), positive surgical margins, tumor recurrence, and metastases correlated with adverse outcome by univariate analysis and, with the exception of mitotic rate, by multivariate analysis. Of the foregoing, tumor diameter, depth of invasion, positive margins, metastases, and tumor recurrence were the most robust predictors of outcome. None of the demographic factors was associated with outcome. This study confirms the poor prognosis of patients with CA. Among all demographic and histologic patterns examined for prognostic significance, tumor diameter, tumor depth of invasion, margin status, tumor recurrence, and metastases emerged as the most important determinants of outcome.

Age Factors↗

Clinicopathologic attributes of common geriatric dermatologic entities.

Certain dermatologic lesions may initially present or be more commonly ascribed to the elderly. These disorders encompass a diverse array of etiologically unrelated degenerative, autoimmune, idiopathic, and neoplastic conditions that may dramatically impact the quality of life and produce significant morbidity and mortality. As the population ages, a more complete understanding of the clinical and histopathologic features unique to the geriatric dermatologic patient is essential.

Acantholysis↗

The miscellaneous blistering disorders.

Historically, the classification of the blistering disorders has been arbitrarily assigned by common clinical features (ie, vesicle, bullae), etiologic factors (ie, infectious, immunologic), or histologic parameters (ie, intraepidermal and subepidermal). There are distinct advantages to each of these classification systems, yet there remain a small number of either common conditions that rarely manifests as a blistering disorder or uncommon conditions that routinely blister, defying conventional classification. Such misfits comprise a miscellaneous group of blistering conditions that merit special consideration.

Bites and Stings↗

Eczema and the spongiotic dermatoses: a histologic and pathogenic update.

The spongiotic dermatoses including eczema and its clinicopathologic variants are capable of presenting in a variety of clinical guises and are pathologically defined by the presence of epithelial intercellular edema that may rarely form blisters. The mechanisms which underlie there pathogensis has only recently begun to be elucidated. Collectively, these disorders comprise an integral facet of dermatology and are the subject of discussion in this article.

Dermatitis, Allergic Contact↗

Changing demographics and pathology of nonmelanoma skin cancer in the last 30 years.

BACKGROUND: Nonmelanoma skin cancer is a common and important public health concern. Few long-term demographic studies to evaluate potential changes in the clinical or pathologic attributes of theses lesions have been initiated. DESIGN: A computer-based archival search of nonmelanoma skin cancer (NMSC) diagnosed in 1972 and 2001 at a large VA medical center was examined with accompanying glass slides. The NMSC consisted of basal cell carcinoma (BCC), invasive squamous cell carcinoma (SCC) and squamous cell carcinoma in situ (SIS). Pathologic attributes examined included the histologic type of BCC (nodular, superficial, infiltrating), and histologic grade of SCC. Demographic features included age, and location. As the majority of patients were men, women were excluded from the study. The results were tabulated and statistically evaluated by the Students' t-test. RESULTS: A total of 831 cases of NMSC diagnosed in 809 patients in 1972 compared to 1,712 cases in 1,011 patients in 2001. BCC accounted for 45%, SIS 23%, and SCC 32% in 1972 compared to 34% BCC (P = .04), 38% SIS (P = .01), and 28% SCC (P > .05) in 2001. Histologic subtypes of BCC included nodular accounted for 45%, superficial 37% and infiltrating 7% in 1972 compared to 35% (P = .05), 46% (P > .05) and 19% (P = .01) in 2001. Among SCC, 79% were well differentiated with 13% moderate and 7% poorly differentiated in 1972 compared with 82% (P > .05), 10% (P >.05), and 8% (P > .05)in 2001. The average age of patients in 1972 was 76.2 and 64.1 in 2001 (P = .02). The most common locations in 1972 are head and neck (H&N) (54%), extremities (24%); 2001 H&N (50%) and extremities (32%, P = .05). CONCLUSIONS: The data would suggest that NMSC is being diagnosed at a younger age and more commonly on the extremities in Veteran's than in the past. The relative proportion of SIS and of superficial and infiltrating BCC is also increasing.

Aged↗

Oncocytic metaplasia occurring in melanoma.

BACKGROUND: Oncocytosis is a cellular feature characterized by the presence of a finely granular eosinophilic cytoplasm due to the accumulation of mitochondria. While this histologic trait can be found in normal tissues, it is also seen pathologically as a degenerative phenomenon. We recently reviewed a spectrum of oncocytic melanocytic nevi that did not have clinical significance. We now describe similar changes in melanoma. METHODS: We retrospectively reviewed 12 melanomas noted to have prominent granular eosinophilic cytoplasm and completed ultrastructural studies. We obtained patient histories and clinical follow-up information from the patients' physicians. RESULTS: All cases were primary melanomas and showed prominent oncocytosis in the majority of the lesional melanoma cells. Oncocytosis was observed in both melanoma in situ and invasive melanoma with a wide range of Breslow thicknesses (range, 0.45-5.05 mm). It occurred in the presence and absence of ulceration, regression, vascular invasion, and brisk tumor infiltrating lymphocytes. Ultrastructural studies revealed melanocytes with numerous distorted mitochondria. CONCLUSION: Melanoma is capable of presenting in a variety of histologic guises, including oncocytic change. While our observations are preliminary, this pathologic curiosity likely represents a degenerative phenomenon of little prognostic importance.

Aged↗

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↗

What is it? Unusual interstitial fibrohistiocytic tumor or other.

Fibrohistiocytic lesions are capable of presenting in a variety of histologic guises. We have recently encountered two lesions that similarly showed a hitherto described proliferation of atypical spindled and stellate cells with a distinctive deep dermal and interstitial distribution. The pathogenic significance and nosologic status of this neoplasm is unknown.

Aged↗