Biomedical subjects

J Bhawan

Publications and source records attributed to J Bhawan.

At least 37 records · Page 2Linked to original sources

PubMed1999

Amelanotic blue nevus: a variant of blue nevus.

Blue nevi are typically heavily melanized. We report a variant of blue nevus that is minimally pigmented. Of the 1,358 blue nevi seen in our laboratory during the last 6 years, 38 (2.7%) were selected that had scant or absent melanin. We refer to these blue nevi as the amelanotic type. Approximately half of the cases in clinical diagnosis were nevus of some type, whereas other differential diagnoses were basal cell carcinoma, dermatofibroma, and lesion. Histologically all specimens were characterized by the spindle-shaped cells seen in blue nevi, but with very little or no obvious melanin. Some lesions were markedly cellular, resembling the features of cellular blue nevus. No hemosiderin was identified on Perls' stain, whereas Fontana-Masson stain was variably positive. Usually there was fibrous stroma. In most cases, the histologic differential diagnosis was dermatofibroma. Other histologic differential diagnoses included amelanotic and/or spindle cell melanoma, dermal Spitz nevus, neurofibroma, and scar. There was no pleomorphism or increased mitotic activity. Evidence of epidermal melanocytic hyperplasia was seen in two cases. Furthermore, the lesions had been present for many years without evidence of recent change. Immunohistochemistry showed all cases to be strongly positive with anti Mel-5 antibody, but only weakly positive or negative with anti S-100 and HMB-45 antibodies. We would like dermatologists and pathologists to be aware of this unusual and uncommon entity.

Adolescent↗

PubMed1999

Histologic features of lichen sclerosus et atrophicus in a surgical scar.

A 76-year-old woman presented with a 7-mm, hard, pink nodule at the site of an appendectomy scar of more than 70 years' duration. The clinical impression at the time of biopsy was that of a keloid. Surprisingly, light microscopic examination revealed classic histologic features of late-stage lichen sclerosus et atrophicus (LSA) overlying a scar. Elastic tissue stain highlighted the unusual presence of abundant nodules of elastin in the reticular dermis only.

Aged↗

PubMed1999

Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR/DGGE)-based detection of clonal T-cell receptor gamma gene rearrangements in paraffin-embedded cutaneous biopsies in cutaneous T-cell lymphoproliferative diseases.

Polymerase chain reaction (PCR)-based amplification of T-cell receptor (TCR)-gamma genes is a novel technique that can detect a clone of T cells comprising less than 1% of the total T cells in a lymphoid infiltrate. Besides greater sensitivity than Southern blotting, this technique can be performed with smaller quantities of lower molecular weight genomic DNA as template. We retrospectively analyzed 12 paraffin-embedded biopsies of cutaneous T-cell lymphoma (CTCL), 1 case suspicious for CTCL, 1 case of granulomatous slack skin, and 8 cases of inflammatory skin diseases to determine if PCR-denaturing gradient gel electrophoresis (PCR-DGGE) analysis can detect TCR-gamma gene rearrangements on paraffin-embedded specimens. We were able to amplify Vgamma1-8 TCR sequences in each case and detected a dominant clone in 9 of 12 cases of CTCL and in granulomatous slack skin. We analyzed Vgamma9 sequences in 9 cases of CTCL and detected a dominant clone in 4 cases. This study demonstrates that PCR-DGGE can easily be applied retrospectively to cutaneous biopsies of lymphoproliferative diseases when fresh tissue is not available.

Adolescent↗

PubMed1999

Identification of mycobacterial DNA in cutaneous lesions of sarcoidosis.

Sarcoidosis is a multisystemic granulomatous disease of uncertain etiology. Recently, mycobacterial DNA especially Mycobacterium tuberculosis and Mycobacterium avium complex were detected in lung tissue and bronchial lavage fluid from patients with sarcoidosis by polymerase chain reaction (PCR) assays in 30% to 50% cases. Moreover, cell wall-defective form (CWDF) acid-fast bacteria have been isolated from skin lesions of patients with sarcoidosis which were later confirmed as M. avium complex by PCR assays. CWDF acid-fast bacteria were also found to grow from the blood of 95% patients with active sarcoidosis demonstrating a mycobacterial origin similar to M. tuberculosis. In view of these reports, we investigated 20 cases of cutaneous sarcoidosis using PCR/restriction enzyme pattern analysis (PCR/REPA) to detect mycobacterial DNA from paraffin-embedded skin biopsy samples. The method involves restriction enzyme analysis of nested PCR products obtained with primers encoding for the 65-KDa protein common to all mycobacteria. Using three restriction enzymes, the mycobacterial DNA from PCR product was differentiated to the species level. All the 20 cases had clinical and histologic evidence of sarcoidosis. Special stains for fungi (PAS) and mycobacteria (Fite) were negative and no foreign body was identified on polaroscopic examination in any of the cases. The cell lysates of M. tuberculosis, Mycobacterium bovis, Mycobacterium avium-intracellulare, Mycobacterium kansasii and Mycobacterium marinum from Centers for Disease Control (CDC) were used as standard control for PCR/REPA. Eight cases of foreign body granuloma, seven normal skin samples from the margin of surgical excisions and 5 cases of dermatitis were used as negative controls, and 4 cases of cutaneous tuberculosis were used as positive controls. Mycobacterial DNA was detected by PCR in 16 of the 20 cases of sarcoidosis. PCR/REPA subtyped 8 of these to M. tuberculosis complex (2 cases), M. avium-intracellulare (4 cases), M. kansasii (2 cases) while the other 8 cases were non-tuberculous mycobacteria. All four cases of cutaneous tuberculosis were positive by PCR and had a typical M. tuberculosis PCR/REPA pattern. Mycobacterial DNA was not detected in any of the negative controls. Our results demonstrated that mycobacterial DNA is present in 80% of cutaneous lesions of sarcoidosis and these mycobacteria may play a role in the pathogenesis of sarcoidosis.

Adult↗

PubMed1998

Mixed Merkel cell carcinoma and squamous cell carcinoma of the skin.

Four mixed Merkel cell and squamous cell carcinomas of the skin are described. The patients ranged in age from 74 to 90 years and demonstrated or had a history of previous ultraviolet or infrared damage to the skin, manifested by basal cell carcinoma, squamous cell carcinoma, actinic keratoses, solar elastosis, and erythema ab igne. Light microscopic examination of all 4 cases revealed invasive neoplasms consisting of 2 distinct but admixed cell types. The predominant cell type was consistent with Merkel cell carcinoma and was characterized by scant cytoplasm, a small dark polygonal nucleus with granular chromatin, a high mitotic rate, and cytokeratin 20 positivity. In each case, the Merkel cell component merged with a cytokeratin 20 negative squamous component characterized by abundant eosinophilic cytoplasm, intercellular bridges, and keratinization with focal squamous pearl formation. Immunohistochemical staining patterns were consistent with the usual pattern for that cell type; transitional cells were not demonstrated. The intimate admixture of the 2 antigenically different neoplastic cell types, and common etiologic role of ultraviolet and possibly infrared damage, lend support to the theory that some Merkel cell carcinomas and squamous cell carcinomas may arise from a pluripotent epidermal stem cell.

Aged↗

PubMed1998

Langerhans cell histiocytosis in the elderly: a report of three cases.

Langerhans cell histiocytosis is most common in children and is unusual in the elderly. We describe 3 cases of langerhans cell histiocytosis limited to the skin in elderly patients. Biopsy specimens showed a dermal infiltrate abutting the epidermis composed of atypical langerhans cells with abundant eosinophilic cytoplasm and a "kidney-shaped" nucleus. Immunoperoxidase stain CD1a was positive in all 3 cases and S-100 stain was positive in 2. Electron microscopy revealed Birbeck granules in the cytoplasm of the atypical langerhans cells in 2 cases. Langerhans cell histiocytosis with skin involvement has a chronic course with an overall good prognosis. However, cutaneous manifestations may precede systemic involvement by many years.

Adult↗

PubMed1998

Pathologic parameters in the diagnosis and prognosis of primary cutaneous melanoma.

Significant progress has been made in the last 10 years on the identification of histologic parameters that are independent predictors of melanoma prognosis, immunohistochemical markers of cells of melanocytic origin and changes in adhesion molecules, cytoskeletal proteins, growth factor receptors, cell signaling, and nuclear proliferation proteins associated with tumor progression. Histologic criteria may never be completely sufficient to predict behavior accurately, because the fundamental change that renders a cell aggressive may not be morphologically reflected and may require immunohistochemical or other molecular markers to establish behavior. To date, it is humbling that no immunohistochemical or molecular marker provides a greater predictable value for aggressive behavior than does the simple calibrated ocular micrometer to measure tumor thickness. Nevertheless, development of multiple histologic parameters with the concept of nontumorigenic RGP and tumorigenic VGP provides a reliable statistical model to predict metastases. Fortunately, nontumorigenic RGP melanomas with greater than 75% regression are rare. Thus, individual patients with melanoma without regression and without the tumorigenic VGP can be given reasonable assurance of 100% survival. Nevertheless, this assurance is based on a statistical model with a finite population studied. Additional studies are needed to confirm this model, as well as more definitive markers to precisely predict outcome for those individuals with tumorigenic VGP melanoma.

Biomarkers, Tumor↗

PubMed1998

Short- and long-term histologic effects of topical tretinoin on photodamaged skin.

BACKGROUND: A series of clinical trials lasting up to 4 years had demonstrated that topical tretinoin improves facial appearance by reducing the visible signs of photodamage. OBJECTIVE: This paper reviews the studies designed to explore the relationship between clinical improvement and histologic changes. METHODS: Histologic changes in biopsies taken at various time points from clinical trial participants were examined by pathologists blinded to treatment regimens. RESULTS: Histologic evaluations of photodamaged skin during the course of treatment with tretinoin have revealed an array of time-dependent morphologic changes which can be classified as early, intermediate, and late. Initial changes in fine wrinkling and texture appear to correlate with epidermal mucin and compaction of the stratum corneum, but the latter is transient and ultimately returns to pre-treatment levels. Alterations in dermal matrix components have been noted with prolonged treatment. Partial restoration of the dermal collagen by new synthesis may contribute to the sustained improvement in fine wrinkling noted even when the treatment frequency is reduced from daily to three times weekly. As treatment is continued beyond 24 months, the collagen organization continues to improve and elastosis continues to decrease. Increases in epidermal and dermal mucin and decreases in epidermal melanin are consistent throughout the treatment period. The reduction in the hyperpigmentation of photodamage is comparable with the histologic and clinical improvements seen when tretinoin is used to treat conditions such as melasma. No adverse effects on the histopathology of the skin are noted with long-term exposure to tretinoin. Neither keratinocyte nor melanocyte atypia is detected. CONCLUSIONS: Although there does not seem to be a direct correlation between histologic changes and clinical improvement, the major structural changes appear to be directed at restoring the skin to the pre-sun-damaged state.

Administration, Topical↗

PubMed1998

Benign sebaceous neoplasm with prominent epidermal component.

A 65-year-old woman presented with a solitary nodule within an erythematous plaque in her right groin. Histopathologic examination showed central lobular proliferation of basaloid cells admixed with mature sebaceous cells and a lateral extensive intraepidermal component composed mostly of lobules of mature sebocytes consistent with intraepidermal epithelioma with sebaceous differentiation and focal invasion. Although various cutaneous neoplasms may show an intraepidermal growth pattern, extensive sebaceous differentiation in such a neoplasm, as seen in this case, has not been described. Electron-microscopic study revealed that the basaloid cells have features of pluripotential cells. This observation supports the previously reported concept that intraepidermal epithelioma may be composed of a group of heterogeneous tumors with various degrees and lines of differentiation. Additionally, sebaceous epithelioma/adenoma should be considered in the differential diagnosis of the cutaneous neoplasms with an intraepidermal growth pattern.

Aged↗

PubMed1998

Multiple pigmented basal cell carcinomas.

Basal cell carcinoma is the most common of all skin cancers and the most prevalent one among Caucasians. Rarely, these tumors are seen in other races. We report a 77-year-old Korean woman who presented with multiple darkly pigmented enlarging nodules on her scalp, face, trunk, and extremities. The patient had first noted a 6-mm pigmented lesion on her left eyebrow 10 years previously. Since then, other lesions had appeared in many locations on her body. She had been otherwise healthy and without a history of exposure to arsenic or radiation. There was no family history of skin cancer, xeroderma pigmentosum, or basal cell nevus syndrome. On physical examination, multiple darkly pigmented dome-shaped papules and nodules were present on her scalp, face, right forearm, lower abdomen, and inguinal areas. They ranged in size from 0.5 mm to 2 cm. The larger ones showed central ulceration. Multiple biopsy specimens from different sites showed pigmented basal cell carcinomas. Clinically, there was no evidence of nevus sebaceus, xeroderma pigmentosum, basal cell nevus syndrome, or immunodeficiency. Clinical workup including chest radiography, abdominal ultrasound, bone scan, and brain computerized axial tomography scan did not demonstrate primary or secondary tumors. The results of serologic and hematologic tests were also within normal limits. This is an unusual case report of multiple pigmented basal cell carcinomas in an Asian woman without any predisposing risk factors.

Aged↗

PubMed1998

Further confirmation of the association of human herpesvirus 8 with Kaposi's sarcoma.

Recently, a new herpesvirus-like DNA sequence named Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) has been isolated from almost all cases of Kaposi's sarcoma (KS). It has not been found in most benign and malignant cutaneous hemangioproliferative disorders other than KS. To further verify the specificity of the association of this new viral DNA with KS, we examined in total 42 cases of vascular neoplasms of endothelial derivation using nested polymerase chain reaction (PCR) for the presence of a 233-bp segment of this KSHV/HHV8 on paraffin-embedded specimens. In our investigation, we added an additional step to conventional PCR protocol that uses UV light to pretreat all the PCR regeants except Taq DNA polymerase and the target DNA to eliminate the false positives caused by trace contamination. All 15 cases of typical KS, both AIDS and non-AIDS related, as well as 4 cases of atypical vascular tumors suspicious of KS, were positive for this KSHV/HHV8 DNA sequence. The remaining 23 cases of hemangioproliferative disorders other than KS, including angiosarcoma, capillary hemangioma, angiolymphoid hyperplasia with eosinophilia, epithelioid hemangioma, histiocytoid hemangioma, hemangioendothelioma, and microvenous hemangioma, were negative for HHV8. These results confirm the previous observation that KSHV/HHV8 is specific for KS within hemangioproliferative cutaneous disorders, and PCR for detection of KSHV/HHV8 might be used as an additional diagnostic tool in distinguishing KS.

Antigens, CD34↗

PubMed1998

In situ and in vitro expression of protein kinase C alpha in human melanocytes.

Protein kinase C (PKC) is a multigene family of at least 12 isoforms involved in the transduction of extracellular signals. We investigated whether PKC-alpha, a major isoform known to be relatively abundant in brain tissue, is increased in human melanocytes relative to keratinocytes in vitro and in situ. Immunohistochemical staining for PKC-alpha in frozen neonatal human foreskin exhibited intermittent 2-3 + staining along the basal cell layer consistent with melanocytes, and 0-1 + staining of keratinocytes (on a scale of 0-3). Microscopic densitometry of the intermittent cellular staining was at least 3-fold greater than that of adjacent keratinocyte cell cytoplasm. Sequential frozen sections revealed similar intermittent cell staining with PKC-alpha and Mel-5 (tyrosinase related protein-1), known to specifically react with melanocytes. Northern blot analysis with a specific cDNA probe for PKC-alpha showed strong PKC-alpha mRNA expression in cultured melanocytes, whereas PKC-alpha mRNA in cultured non-stratifying keratinocytes was expressed at low levels. Western blot analysis revealed a prominent PKC-alpha band at approximately 80 kDa in melanocytes as opposed to a weak band in keratinocytes. Densitometry of the northern and western blots revealed that melanocytes had at least 10-fold more PKC-alpha mRNA and approximately 6-fold more PKC-alpha protein expression than keratinocytes. Total PKC activity measured in vitro revealed that melanocytes had 5-fold more activity than keratinocytes. The marked difference in melanocyte and keratinocyte expression of PKC-alpha provides further evidence for cell type specificity in the balance of PKC-alpha expression and may implicate differential PKC isoform signaling pathways in neuro-ectodermally derived cells.

Blotting, Northern↗

PubMed1998

Burn scar carcinoma. Diagnosis and management.

BACKGROUND: The term Marjolin ulcer is now synonymous with malignant transformation of chronic ulcers, sinus tracts, and burn scars. OBJECTIVE: To illustrate the importance of incisional or excisional biopsies in cases of suspected burn scar carcinoma. METHODS: Case report and review of the literature. RESULTS: Multiple punch biopsies were negative while a complete excision revealed the diagnosis of squamous cell carcinoma. CONCLUSION: Because of the focal nature of malignant change in burn scars, incisional or excisional biopsy should be performed.

Abdomen↗

PubMed1997

Histopathology of solar lentigines of the face: a quantitative study.

BACKGROUND: Solar lentigines are acquired pigmented lesions on sun-damaged skin that in general have both keratinocytic and melanocytic hyperplasia, but no melanocytic atypia and no nests of melanocytes. Most histopathologic studies of solar lentigines have been limited to sites other than the face and have not included a systematic and quantitative assessment of the diagnostic features. OBJECTIVE: Our purpose was to systematically quantitate a variety of histologic parameters that may be useful in the diagnosis of facial solar lentigines. METHODS: We retrospectively evaluated 51 solar lentigines from 51 patients. This included a review of the hematoxylin-eosin, Mel-5 immunoperoxidase, and Fontana-Masson stains to quantify melanocytes (per millimeter), melanin content of the epidermis, and epidermal area by means of a computer-assisted image analysis program. RESULTS: Lentigines from the face often had a flattened epidermis (25 of 51). They also had a mean 2.1-fold increase in melanocytes (p < 0.001), a 2.1-fold increase in epidermal area (p < 0.001), and a 2.2-fold increase in epidermal melanin content (p < 0.001) compared with normal photoexposed facial skin. CONCLUSION: Facial solar lentigines had a statistically significant twofold increase in both epidermal area and number of melanocytes compared with facial skin with a similar degree of photodamage, but frequently lacked the rete ridge hyperplasia classically associated with lentigines from other anatomic sites. These morphologic data may be helpful in the evaluation of biopsy specimens from pigmented lesions on photodamaged facial skin.

Aged↗

PubMed1997

Ultrastructural evidence for the participation of Langerhans cells in cutaneous photoaging processes: a quantitative comparative study.

Langerhans cells were studied comparatively by electron microscopy in order to explore their possible participation in cutaneous photoaging processes in chronically photodamaged preauricular skin and in paired sun-protected postauricular sites of 25 Caucasian women aged 56-76 years. The characteristic ultrastructural features of Langerhans cells in photodamaged skin compared to those in sun-protected skin were as follows: (1) a significant decrease in the density of Langerhans cells and Birbeck granules, and an increase in the number of indeterminate cells, (2) an inversely proportional relationship between intraepidermal density of Langerhans cells and the severity of epidermal photodamage, (3) frequent apposition of Langerhans cells to vacuolar structures of photodamaged keratinocytes, (4) predominant distribution of Langerhans cells in the lower epidermis, (5) degenerative changes suggesting direct cellular damage, without evidence of apoptosis, (6) a strong correlation of the number of degenerated Langerhans cells with the degree of epidermal photodamage, (7) loss of dendritic processes, (8) direct contact of Langerhans cells with melanocytes suggesting interaction between these two types of cells, (9) juxtaposition of Langerhans cells and lymphocytes in the epidermis. These results suggest marked qualitative and quantitative ultrastructural differences in Langerhans cells between photodamaged and intrinsically aged skin and the positive involvement of Langerhans cells in the processes of cutaneous photoaging.

Aged↗

PubMed1997

Diffuse hyperpigmentation of the skin: a clinicopathologic approach to diagnosis.

There are multiple causes of diffuse hyperpigmentation of the skin (DHP) and determination of the exact etiology can sometimes be difficult. A systematic classification based on both clinical and pathological findings that should aid the clinician who is confronted with this situation is presented in this article. The skin diseases that cause DHP are classified based on the pigment characteristics (melanin, non-melanin), pigment distribution (epidermal, epidermal-dermal, dermal) and density of melanocytes (normal, increased). The intent of this review is to provide a "histopathological tool" that increases diagnostic accuracy in the evaluation of a patient with DHP.

Cell Count↗

PubMed1997

Mel-5: a novel antibody for differential diagnosis of epidermal pigmented lesions of the skin in paraffin-embedded sections.

Histological evaluation of epidermal melanocytes on routine staining is difficult and cannot be made with accuracy. Widely known antibodies such as S-100 and HMB-45 are unreliable for normal epidermal melanocytes. Furthermore, S-100 stains other cells including Langerhans' cells. Results of incubation with DOPA are inconsistent and the procedure is time-consuming. We have evaluated the use of Mel-5, an antibody that was developed against melanoma and melanocytes. This antibody is a mouse monoclonal antibody that specifically detects a 75 kDa glycoprotein usually expressed by normal melanocytes, naevi and melanoma cells in routinely fixed paraffin sections. Histological differentiation between pigmented actinic keratosis in photodamaged skin and lentigo maligna can be difficult. The atypical keratinocytes, particularly in the basal layer, can be confused with atypical melanocytes, especially if they are pigmented. Similarly, distinctions between lichen planus-like keratosis and lichenoid melanoma in situ and lentigo maligna and lentigo may be difficult. Use of Mel-5 in such cases has shown consistent results in separating melanocytic from non-melanocytic lesions. This antibody is also helpful in evaluating biopsies of patients with vitiligo, post-inflammatory pigmentary alteration and regressed or regressing melanocytic lesions. Furthermore, Mel-5 is an invaluable tool in quantification of epidermal melanocytes in research projects.

Animals↗

PubMed1997

Penile verrucous carcinoma in a 37-year-old circumcised man.

Squamous cell carcinoma of the penis is almost exclusively a lesion of uncircumcised older men. It represents about 1% of cancers in men in the United States and 11% to 12% of all cancers in men in countries where circumcision is not routinely practiced. Verrucous carcinoma is an uncommon variant that accounts for only 5% to 16% of all penile squamous cell carcinomas. We describe penile verrucous carcinoma in a 37-year-old white man who had been circumcised in infancy. To our knowledge this is the first case report of verrucous carcinoma in a circumcised man without any predisposing penile anatomic abnormalities.

Adult↗