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Rossitza Lazova

Publications and source records attributed to Rossitza Lazova.

15 recordsLinked to original sources

Expression of tumor necrosis factor--related apoptosis-inducing ligand receptors 1 and 2 in melanoma.

PURPOSE: The proapoptotic receptors tumor necrosis factor--related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and TRAIL-R2 are targets of drugs in clinical development, and receptor expression levels may be important determinants of sensitivity to receptor agonists. We assessed TRAIL-R1 and TRAIL-R2 expression patterns in a large cohort of melanomas and benign nevi. EXPERIMENTAL DESIGN: We analyzed tissue microarrays containing 546 melanomas and 540 nevi using our automated quantitative method to measure protein levels in situ (AQUA). The system uses S100 to define pixels as melanoma (tumor mask) within the array spot and measures intensity of TRAIL-receptor expression using Cy5-conjugated antibodies within the mask. AQUA scores were correlated with clinical and pathologic variables. RESULTS: TRAIL-R1 and TRAIL-R2 expression was higher in melanomas than in nevi (P < 0.0001), and higher in primary than in metastatic specimens (P = 0.0031 and P < 0.0001, respectively). TRAIL-R1 and TRAIL-R2 expression exceeding the 95th percentile for nevi was found in 19% and 74% of melanoma specimens, respectively. Although on univariate analysis, high TRAIL-R2 expression correlated with increased survival (P = 0.0439), it was not associated with survival within the primary or metastatic subcohorts. TRAIL-R1 expression was not associated with survival. CONCLUSIONS: TRAIL-R1 and TRAIL-R2 expression is higher in malignant melanocytes than in their benign counterparts, suggesting that these receptors might be effective therapeutic targets in melanoma. Expression is higher in early-stage disease than in metastatic specimens, and expression exceeding that found in nevi is found in a substantially larger fraction of melanomas for TRAIL-R2 compared with TRAIL-R1. Assessment of baseline tumor TRAIL receptor expression may be important in analysis of clinical trials involving TRAIL receptor agonists.

Gene Expression Regulation↗

Calcinosis cutis: a complication of intravenous administration of calcium glucanate.

Calcinosis cutis, the deposition of calcium in the dermis, can be dystrophic, metastatic, iatrogenic, or idiopathic. Here, we describe a case of iatrogenic calcinosis cutis secondary to extravasation of an intravenous calcium-containing solution in a child. We also review the literature regarding the pathogenic mechanisms involved in the development of calcinosis cutis after extravasation injuries. While iatrogenic calcinosis cutis is generally a benign entity, it is important to recognize its unique clinical and histopathologic presentation to avoid complications from misdiagnosis.

Calcinosis↗

Iron in skin of mice with three etiologies of systemic iron overload.

In human hemochromatosis, tissue toxicity is a function of tissue iron levels. Despite reports of skin toxicity in hemochromatosis, little is known about iron levels in skin of individuals with systemic iron overload. We measured skin iron and studied skin histology in three mouse models of systemic iron overload: mice with a deletion of the hemochromatosis (Hfe) gene, mice fed a high iron diet, and mice given parenteral injections of iron. In Hfe(-/-) mice, iron content in the epidermis and dermis was unexpectedly the same as in Hfe(+/+) mice, and there were no histological abnormalities detected after 30 wk. A high iron diet produced increased iron in the epidermis of both normal and Hfe(-/-) animals; a high diet increased iron in the dermis only in Hfe(-/-) mice. Increased skin iron was not associated with other histological changes, even after 19 wk. Parenteral administration of iron produced increased iron in the epidermis and dermis, and gave the skin a bronze hue. These results show that the amount and distribution of iron in the skin depends on the etiology of iron overload. It appears that neither Hfe deletion nor elevated skin iron alone can account for cutaneous manifestations reportedly seen in humans with hereditary hemochromatosis.

Animals↗

The characteristic histopathologic features of nevi on and around the ear.

BACKGROUND: Nevi on certain areas of the body such as the acral, genital, and flexural regions may exhibit uncommon but characteristic histopathologic features. The purpose of this study was to characterize the distinctive features of nevi with a junctional component located on and around the ear. MATERIALS AND METHODS: A total of 101 compound and junctional nevi of the ear received at the Yale Dermatopathology Laboratory during a 10-year period were examined in this study. The most characteristic feature of the majority of these nevi was irregularity of nesting pattern, with nests, which varied in size and shape and which were sometimes located between rete ridges. RESULTS: Forty-two (42%) of nevi on and around the ear showed poor circumscription, lateral extension of the junctional component beyond the dermal component, and elongation of rete ridges with bridging between them. A subset of these nevi (26 cases) showed uniformly large melanocytes with large vesicular nuclei without prominent nucleoli, and abundant pale, finely granular cytoplasm. These lesions did not show a tendency to recur. CONCLUSIONS: This study supports the existence of a subset of nevi on or near the ear that, like certain nevi located on other special sites, exhibit unusual but characteristic features, which may be misinterpreted as atypical or malignant.

Adolescent↗

Cellular digital fibromas: distinctive CD34-positive lesions that may mimic dermatofibrosarcoma protuberans.

BACKGROUND: Digital fibromas are common benign acral tumors typically reported as angiofibromas (AFs) or acquired digital fibrokeratomas (ADFs). Cellular variants are not well recognized. METHODS: We collected 14 acral fibrocytic lesions showing a spindle cell morphology from our files, and evaluated CD34, Factor XIIIa, epithelial membrane antigen (EMA), and S100 protein staining of these lesions. We compared the histologic and immunohistochemical features of these cellular fibromas with five digital AFs, five ADFs, and five digital dermatofibromas. RESULTS: The 14 cellular digital fibromas showed intersecting fascicles of thin delicate bland spindle cells in the superficial reticular dermis with a fibrotic-to-slight myxoid stroma. The spindle cells in all cases stained strongly for CD34, and only scattered stromal cells stained for Factor XIIIa. Five tested cases were negative for EMA and S100 protein. The digital AFs, fibrokeratomas, and dermatofibromas stained predominately for Factor XIIIa, with no or minimal staining for CD34. CONCLUSIONS: These findings suggest that a subset of digital fibromas is characterized by a dense cellular proliferation of CD34-positive spindle cells. Awareness of this variant of digital fibroma and its staining pattern is critical in preventing misdiagnosis as dermatofibrosarcoma protuberans, particularly in superficial biopsies.

Adult↗

Minocycline hyperpigmentation isolated to the subcutaneous fat.

We present a 15-year-old girl with bilateral lower extremity discoloration of one-year duration while taking minocycline for acne vulgaris. The clinical characteristics best supported type II minocycline hyperpigmentation, but the histology revealed that the pigmentation was solely limited to the subcutaneous adipose tissue, completely sparing the dermis. Special stain for iron was negative. This is the first case to our knowledge with pigment exclusively located in the subcutaneous fat and with the unusual finding of a negative stain for iron.

Acne Vulgaris↗

CD56 staining in Merkel cell carcinoma and natural killer-cell lymphoma: magic bullet, diagnostic pitfall, or both?

BACKGROUND: Antibodies to CD56 label natural killer (NK) cell lymphomas and neuroendocrine tumors such as Merkel cell carcinoma (MCC). In MCC altered by crush artifact or obscured by lymphocytes, the histologic features coupled with CD56 positivity can lead to an erroneous impression of NK-cell lymphoma. METHODS: Eighteen cases of MCC were stained for CD56, CK20, MNF116, and pankeratin. The results were compared to histologic features and CD56 staining pattern of three NK-cell lymphomas. RESULTS: Three of 18 cases of MCC histologically resembled lymphoma, and CD56 positivity with CD3 and CD20 negativity initially raised the possibility of NK-cell lymphoma. Two additional cases were obscured by dense inflammation, again suggesting the diagnosis of lymphoma. Seventeen of 18 MCC labeled for CD56 and an equal number stained for CK20. All MCC tested were positive for CAM5.2 (14/14) and MNF116 (17/17). Antibodies to pankeratin labeled only one of 18 MCC. Staining for CD56 was stronger in MCC than NK-cell lymphomas. CONCLUSIONS: CD56 is a sensitive marker for MCC as well as for NK-cell lymphoma, but is not specific. Importantly, CD56 positivity in crushed or inflamed biopsies of MCC may lead to an erroneous impression of NK lymphoma. Awareness of this potential pitfall will prevent misdiagnosis. McNiff JM, Cowper SE, Lazova R, Subtil A, Glusac EJ. CD56 staining in Merkel cell carcinoma and natural killer-cell lymphoma: Magic bullet, diagnostic pitfall, or both?

Aged↗

Calciphylaxis associated with acute, reversible renal failure in the setting of alcoholic cirrhosis.

We describe a case of calciphylaxis in a 47-year-old man with alcohol-induced end-stage liver disease and acute renal failure secondary to hepatorenal syndrome. Possible contributing factors included transiently impaired renal function, protein C and S deficiencies, elevated calcium-phosphate product, hyperphosphatemia, low serum albumin, repeated albumin infusions, and elevated alkaline phosphatase level.

Acute Kidney Injury↗

Scar-localized argyria secondary to silver sulfadiazine cream.

Silver sulfadiazine cream is a topical antibacterial agent that combines the antibacterial effects of both silver and sulfadiazine. Its reported cutaneous side effects include hypersensitivity reactions, allergic contact dermatitis, erythema multiforme, and systemic argyria. We report the case of a patient who had localized argyria develop in a scar after the use of silver sulfadiazine cream. In this case, the silver sulfadiazine cream was applied to and argyria developed within a postsurgical wound and area of severe contact dermatitis.

Administration, Cutaneous↗

Cutaneous natural killer/T-cell lymphoma.

Lymphomas are classified as either Hodgkin's or non-Hodgkin's. The 2 subtypes of non-Hodgkin's lymphoma that can present primarily in the skin are cutaneous T-cell lymphoma and cutaneous B-cell lymphoma, both of which tend to be low-grade malignant neoplasms. Recently another distinct subtype of lymphoma was discovered, the natural killer (NK)/T-cell lymphoma, which can involve the skin in a primary or secondary fashion. The NK/T-cell subtype of lymphoma is characterized by the expression of the NK-cell antigen CD56. These CD56(+) lymphomas are further subdivided into nasal NK/T-cell lymphomas that commonly present as midfacial destructive disease and non-nasal NK/T-cell lymphomas that often arise in extranodal locations, including the skin. We report a case of aggressive NK-cell leukemia/lymphoma with numerous secondary cutaneous lesions and review the clinical and histopathologic spectrum of non-nasal CD56(+) lymphomas, with an emphasis on the dermatologic findings.

Aged↗

Cutaneous larva migrans with parts of the larva in the epidermis.

Creeping eruption is usually caused by hookworms, most commonly Ancylostoma braziliensis and Ancylostoma caninum. Because lesions of cutaneous larva migrans have a typical clinical appearance, they are rarely biopsied. Specimens usually show spongiotic dermatitis with spongiotic vesicles containing neutrophils and eosinophils and a mixed-cell dermal infiltrate with numerous eosinophils. We report a case with parts of the larva migrans in the epidermis on histologic examination.

Adult↗

Subcutaneous fat necrosis of the newborn presenting as a large plaque with lobulated cystic areas.

Subcutaneous fat necrosis of the newborn (SFN) usually occurs in the first few weeks of life in full-term infants and presents as indurated, distinct nodules with a predilection for the cheeks, shoulders, back, buttocks, and proximal extremities. Most cases are related to some form of fetal distress, including obstetric trauma. Some cases are associated with hypercalcemia. We report a case of SFN with an unusual clinical presentation, complicated by hypercalcemia.

Biopsy, Needle↗

Fatal childhood calciphylaxis in a 10-year-old and literature review.

Calciphylaxis is a rare but highly morbid disorder of vascular calcification and skin necrosis, affecting 1% to 4% of adults with end-stage renal disease. Only three affected children have previously been described. We report an unusual instance of fatal calciphylaxis involving a 10-year-old boy, in the setting of sarcoidosis-induced end-stage renal disease. A review of pediatric calciphylaxis cases suggests: (a) increased risk in boys with end-stage renal disease and secondary hyperparathyroidism; (b) frequent distal extremity and visceral organ involvement, (c) worse prognosis with acral necrosis, and (d) possible increased resistance to medical treatment compared to adult patients. Hyperesthetic pain is a common sentinel symptom, and soft tissue x-rays or xeroradiography or both may aid in the diagnosis of pediatric calciphylaxis. Parathyroidectomy in combination with supportive medical management may be the best treatment option in stopping the progression of disease in the pediatric population.

Calciphylaxis↗