Assessing smoldering adult T cell leukemia/lymphoma: a case report.

Adult T cell leukemia/lymphoma (ATLL) is a rare, extremely aggressive malignancy with four different clinical variants, all of which are associated with human T cell lymphotropic virus type 1. Antiretrovirals have been recognized as an effective therapy after study in clinical trials around the world. However, oncologists traditionally wait for asymptomatic patients with ATLL to reach a more severe stage of disease before treatment is initiated. We describe a patient with Fitzpatrick Skin Type V who presented with asymptomatic dyschromia of her neck, breast, and jaw. Her clinical, laboratory, and histological findings were consistent with smoldering type-ATLL. We teamed up with her oncologist to successfully treat her cutaneous symptoms with interferon-alpha/zidovudine. This report demonstrates efficacy with the employment of antiretroviral therapy immediately following a diagnosis of smoldering type ATLL.

An immunohistochemical panel to assess ultraviolet radiation-associated oxidative skin injury.

Ultraviolet (UV) radiation results in a significant loss in years of healthy life, approximately 1.5 million disability-adjusted life years (DALYs), and is associated with greater than 60,000 deaths annually worldwide that are attributed to melanoma and other skin cancers. Currently, there are no standardized biomarkers or assay panels to assess oxidative stress skin injury patterns in human skin exposed to ionizing radiation. Using biopsy specimens from chronic solar UV-exposed and UV-protected skin, we demonstrate that UV radiation-induced oxidative skin injury can be evaluated by an immunohistochemical panel that stains 8-hydroxydeoxyguanosine (8-OH-dG) to assess DNA adducts, 4-hydroxy-2-nonenal (HNE) to assess lipid peroxidation, and advanced glycation end products (AGEs) to assess protein damage. We believe this panel contains the necessary cellular biomarkers to evaluate topical agents, such as sunscreens and anti-oxidants that are designed to prevent oxidative skin damage and may reduce UV-associated skin aging, carcinogenesis, and inflammatory skin diseases. We envision that this panel will become an important tool for researchers developing topical agents to protect against UV radiation and other oxidants and ultimately lead to reductions in lost years of healthy life, DALYs, and annual deaths associated with UV radiation.

Microcystic adnexal carcinoma of the vulva.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a subset of sweat gland carcinoma first described as a specific entity by D. J. Goldstein, R. J. Barr, and D. J. Santa Cruz (Cancer 1982;50:566-72). We report the first case of MAC occurring on the vulva and review the literature pertaining to this rare tumor. CASE: A 43-year-old multiparous black woman presented initially to Kings County Hospital Medical Center with a chief complaint of a vulvar lesion arising on the left labia majora which she had noted for 4 years prior to presentation. Aside from increasing paresthesia in the area, she denied any constitutional symptoms. Her past medical history was significant only for hyperthyroidism and mild hypertension and surgical history was noncontributory. Gynecologic history was unremarkable, with sporadic care over the last 20 years. Physical examination revealed a 1.5 x 2.0-cm raised, well-circumscribed, firm mobile lesion on the left labia majora. It was noted to be yellow in color with the surrounding tissue being unremarkable in character. The remainder of her gynecologic examination and lymph node survey was unremarkable. Preoperative chest X ray was negative as was the CAT scan of the abdomen and pelvis. All laboratory values were within normal limits. A Pap smear done preoperatively was significant for atypical squamous and glandular cells of undetermined significance. Subsequent colposcopic examination of the cervix was remarkable for cervicitis and was adequate, with the entire transformation zone visualized. Both endocervical curettage and endometrial biopsy were normal. Initially, an excisional biopsy was performed with final pathology demonstrating microcystic adnexal carcinoma with positive surgical margins. She subsequently underwent a left radical hemivulvectomy with bilateral inguinal groin lymph node dissection. At the time of surgery, the left labia majora was noted to be well healed, with a residual surgical scar easily discernible. No areas of discoloration were noted and digital palpation of the area was unremarkable. Microscopic residual tumor was noted; however, all surgical margins and lymph nodes were negative for tumor. Her postoperative course was unremarkable. The patient has continued to do well since the time of her surgery and is being followed conservatively. CONCLUSION: Radical vulvectomy should be performed when MAC occurs in the vulva to secure negative margins of resection. Groin dissection should be reserved for cases in which the inguinal lymph nodes are clinically suspicious or in cases of tumor recurrence.

The use of hairless (IAF/HA-HO) guinea pigs for the determination of delayed-type hypersensitivity to tuberculin.

Guinea pigs are a classic animal model for studying delayed-type hypersensitivity (DTH) reactions. However, skin irritation due to hair removal can interfere with the evaluation of the modulation of these responses by various mediators. A DTH model using hairless (IAF/HA-HO) guinea pigs, sensitized with complete Freund's adjuvant and repeatedly skin tested with tuberculin, purified protein derivative, (PPD) has therefore been developed. At 10 weeks after sensitization, intradermal PPD elicited minimal erythema at 6 h, which increased over the next 18 h to a maximum at 24 h, and declined by 48 h. The response could be quantified by bioassay using graded doses of PPD. Reactions at 24 h were characterized by predominantly mononuclear cell deep and superficial dermal infiltrates. Dermal DTH in hairless guinea pigs is thus, grossly and histologically similar to that seen in Hartley guinea pigs.

Outer root sheath acanthoma.

The term "outer root sheath acanthoma" is proposed to specify a distinctive keratosis exhibiting outer root sheath differentiation. This lesion features anastamosing columns of keratinocytes emanating from the undersurface of the epidermis that respectively demonstrate, with progressive descent into the upper dermis, outer root sheath differentiation characteristic of the infundibulum, isthmus, stem and anagen bulb. In our patient, the lesion was solitary, and no associated systemic disease was evident. Outer root sheath acanthoma is a unique keratosis displaying all four types of tricholemmal differentiation, thus representing a true neoplasm of the entire outer root sheath.

Attentional bias in normal subjects performing visual and tactile radial line bisections.

Misbisection of lines is thought to represent an attentional bias. When radial lines (intersection of the midsagittal and transverse planes) are presented below eye level, normal subjects are biased toward far peripersonal space in the visual modality and to near peripersonal space in the tactile modality. These errors may be related to a body centered, a retinotopic, or an object centered attentional bias. The purpose of this study was to contrast the body centered and retinotopic-objective centered hypotheses by having 12 normal subjects perform visual and tactile bisections of radial lines that are above and below eye level. The top of the page, which may be defined by retinotopic or object centered coordinates, contains the portion of the line that is most distant from our bodies when the page is below eye level. However, above eye level, the top of a radial line would be the portion of the page that is most proximal to our bodies. We observed that when stimuli are presented below eye level, normal subjects have a visual bias toward far peripersonal space or the top of the page or both, and have a tactile bias in the opposite direction. In the above eye position we found no overall bias in either modality. Because above eye level the body centered bias should have remained the same but the retinotopic or object centered bias should have reversed, our results suggest that the body and object centered or retinotopic biases, which are oriented in opposite directions, nullified each other.

Eccrine syringofibroadenoma surrounding a squamous cell carcinoma: a case report.

A 91-year-old man presented with a 9.0 x 7.0 cm exophytic mass on the dorsum of the right foot, surrounded by a scaling hyperkeratotic plaque-like lesion that had been present for many years. He had similar long-standing hyperkeratotic plaque-like lesions on both legs. Histopathologic examination of the exophytic mass revealed a well-differentiated squamous cell carcinoma surrounded by an eccrine syringofibroadenoma (ESFA). Histochemistry, immunohistochemistry and electron microscopy support this diagnosis. To our knowledge, this is the only reported case of ESFA being intimately associated with a malignant neoplasm.

Leukotriene B4 modulates in vivo expression of delayed-type hypersensitivity by a receptor-mediated mechanism: regulation by lipoxin A4.

Leukotriene B4 (LTB4) is a potent proinflammatory arachidonic acid metabolite whose actions are mediated by specific receptors. Recent characterization of a high-affinity LTB4 receptor on the surface of guinea pig CD4+ T lymphocytes prompted examination of a possible role of LTB4 in modulating in vivo expression of delayed-type hypersensitivity (DTH) to tuberculin (PPD). In the absence of PPD, intradermal injections of LTB4 or LTB4/LTD4 receptor antagonists did not elicit delayed-onset erythema at 24 h. When injected together with PPD, LTB4 (1 fmol to 1 pmol) caused a significant 25 to 30% decrease in DTH expression, whereas LTB4 receptor antagonists SC-41930, LY-223982, ONO-4057 (0.1-10 nmol), caused a highly significant (P < .01) 25 to 50% increase. The effect of SC-41930 on DTH expression was inhibited by a 10-fmol dose of LTB4. LTD4 receptor antagonist LY-171883 had no effect on DTH expression. Lipoxin A4 (LXA4) interferes with binding of LTB4 to T lymphocytes or neutrophils by reducing LTB4 receptor density. It caused a small but significant enhancement of DTH expression at 1-nmol doses when injected with PPD. Lipoxin B4 had no effect. Enhancement or inhibition of grossly visible delayed skin responses to PPD by LTB4. LTB4 receptor antagonists or LXA4 was not associated with qualitative or quantitative changes in superficial or deep dermal mononuclear cell infiltrates at the reaction site. We conclude that LTB4 modulates visible expression of DTH in vivo by a receptor-mediated mechanism.

Papular mucinosis and human immunodeficiency virus infection.

Cutaneous mucin deposition occurs both as an isolated phenomenon and in patients with various systemic disorders. Among these are endocrinopathies (eg, hypo- and hyperthyroidism), malignancy (mycosis fungoides), connective tissue disorders (lupus erythematosus), and infectious diseases (scleredema associated with upper respiratory tract infection). We present a case of papular mucinosis in a patient infected with the human immunodeficiency virus. This case represents the third report of these disorders coexisting.

Enhancement of delayed hypersensitivity inflammatory reactions in guinea pig skin by 12(R)-hydroxy-5,8,14-eicosatrienoic acid.

Delayed-type hypersensitivity (DTH) reactions are initiated by sensitized T cells. Their progression is dependent upon the local release of various autacoids, including cytokines and eicosanoids, by T cells, infiltrating inflammatory cells, and resident tissue cells. 12(R)-hydroxy-5,8,14-eicosatrienoic acid [12(R)-HETrE], an eicosanoid produced by skin and cornea, possesses potent proinflammatory properties at picomolar concentrations including vasodilation, increase in membrane permeability, neutrophil chemotaxis, and angiogenesis. Because DTH reactions are associated with many of these same phenomena, we examined the effect of 12(R)-HETrE and related 12-hydroxyeicosanoids on the expression of DTH to purified protein derivative of tuberculin in sensitized guinea pigs. In the absence of purified protein derivative of tuberculin, none of the eicosanoids evoked erythema or edema after intradermal injection at doses up to 100 pmol. When injected together with purified protein derivative of tuberculin, 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid [12(R)-HETE], but not its enantiomer 12(S)-HETE, significantly inhibited macroscopic expression of delayed reactivity (erythema) only at the highest dose tested, 10 pmol. In contrast, 12(R)-HETrE significantly enhanced expression of DTH at doses between 1 fmol and 1 pmol (50% and 30% increases above control, respectively). Its stereoisomer, 12(S)-HETrE, did not enhance DTH at any tested dose, but was able to block the activity of 12(R)-HETrE when injected simultaneously. Enhancement or inhibition of visible skin responses was not associated with qualitative or quantitative changes in cellular infiltrates at the reaction site. 12(R)-HETrE had no effect on the nonimmunologic inflammatory skin reaction induced by phorbol myristate acetate, suggesting selectivity toward DTH. We conclude that 12(R)-HETrE enhances DTH via a yet to be determined mechanism and that its stereoisomer, 12(S)-HETrE, may be a useful antagonist for studying the inflammatory actions of this eicosanoid.

Volume of malignant melanoma is superior to thickness as a prognostic indicator. Preliminary observation.

There are many clinical and histologic factors that are known to be valuable in predicting survival rates for patients with cutaneous malignant melanomas. Breslow thickness is considered to be the most reliable prognostic factor; however, thickness is a unidimensional measurement. A more accurate mensuration to predict biologic behavior might be one that takes into account the three-dimensional volume of the neoplasm. In a study of 35 primary malignant melanomas, the volumes of the dermal components of the tumors were calculated. Those patients with tumor volumes of 200 mm3 or less had a 91.4% 5-year disease-free survival rate, compared with survival rate of only 16.7% for those patients whose lesions had tumor volumes exceeding 200 mm3. On multivariate analysis, tumor volume exceeded thickness as a prognostic indicator. Thus, measurement of tumor volume proved to be of greater significance than thickness in predicting the outcome for patients with malignant melanomas.

Distinguishing benign and malignant melanocytic lesions with the AgNOR method.

A silver staining technique has recently been devised to aid in the differentiation between benign and malignant melanocytic lesions. This study showed a statistically significant difference between the staining of silver-nucleolar organizer regions (AgNORs) in melanocytic nevi and that of AgNORs in malignant melanomas.

The histopathology of dysplastic nevi. Continued controversy.

The histopathologic criteria used in the diagnosis of dysplastic nevi have been a source of controversy, as has the clinical significance of these lesions. Several dermatopathologists noted for their work on dysplastic nevi were asked to contribute responses to questions regarding the architectural and cytological criteria used to classify a melanocytic nevus as dysplastic, the terminology used to describe these lesions, and the role of dysplastic nevi as precursors of melanoma. Although no consensus has been reached regarding the cytologic features required for diagnosis of dysplastic nevi, there is substantial agreement regarding the architectural features of these lesions.

Spitz nevi in black children.

Four black children with Spitz nevi are presented. The initial clinical diagnosis was pyogenic granuloma for three patients. One child had two Spitz nevi. Histologic examination revealed melanocytic dendritic hyperplasia in all cases.

Widespread flat warts associated with human papillomavirus type 5: a cutaneous manifestation of human immunodeficiency virus infection.

Numerous flat and tinea versicolor-like warts developed on the face, trunk, and upper extremities of a 10-year-old boy with human immunodeficiency virus infection. Nucleic acid analysis of involved skin revealed human papillomavirus type 5, which has sometimes been associated with epidermodysplasia verruciformis. This human papillomavirus type has also been described in patients with common variable immunodeficiency and dyskeratosis congenita and in renal allograft recipients. Human immunodeficiency virus infection should be added to the list of immune-related disorders that predispose to widespread flat warts.