Maria Miteva

Spitz nevus and atypical spitzoid neoplasm.

Spitz nevus (SN) and Spitzoid malignant melanoma (SMM) represent benign and malignant counterparts at both ends of the spectrum of Spitzoid lesions. Atypical Spitzoid neoplasm (ASN) is a poorly defined and characterized category of melanocytic tumors with histologic features of both benign Spitz nevi and malignant melanomas. The group of ASN represents a mixture of Spitz nevi with atypical features and Spitzoid melanomas. However, at the current moment in time, histopathologists are not capable of differentiating between the 2 in some cases and are forced to place them in this ambiguous category, where the behavior of these lesions cannot be predicted with certainty. Because this group encompasses both benign and malignant lesions, and perhaps also a separate category of melanocytic tumors that behave better than conventional melanomas, some of these neoplasms can metastasize and kill patients, whereas others have no metastatic potential, and yet others might only metastasize to regional lymph nodes. Although diagnostic accuracy has improved over the years, many of these lesions remain controversial, and there is still poor interobserver agreement in classifying problematic Spitzoid lesions among experienced dermatopathologists. The objective of this review article is to summarize the most relevant information about SN and ASNs. At this time histologic examination remains the golden standard for diagnosing these melanocytic neoplasms. We therefore concentrate on the histopathologic, clinical, and dermoscopic aspects of these lesions. We also review the most recent advances in immunohistochemical and molecular diagnostics as well as discuss the controversies and dilemma regarding whether to consider sentinel lymph node biopsy for diagnostically ambiguous melanocytic neoplasms.

Papuloerythroderma 2009: Two New Cases and Systematic Review of the Worldwide Literature 25 Years after Its Identification by Ofuji et al.

Background: Even after the description of papuloerythroderma of Ofuji (PEO) in 1984, little is known about this clinical entity. Objective:To report on 2 new cases of PEO and review of the worldwide literature on this topic. Methods: Article citations were searched on several biomedical search engines (PubMed, EMBASE, SCOPUS, Google Scholar). Papers were retrieved either online or in print. Results: A grand total of 170 PEO cases were identified. Most patients were older than 55 years and of Asian or white descent, with an overall male/female ratio of 4.0. Itch and the deck-chair sign were observed in all patients. Peripheral eosinophilia, lymphocytopenia and increased serum IgE were common findings. Histopathology mostly showed aspecific inflammation, while 17 showed histological features of cutaneous T-cell lymphoma (CTCL). Atopy, malignancies, infections and drugs were rarely linked to PEO. Conclusion: PEO represents a rather monomorphous entity both clinically and, with the remarkable exception of CTCL, also histologically. Nonetheless, no causative factor could be identified in the vast majority of cases. An etiological classification and diagnostic criteria are proposed in the attempt to contribute framing this puzzling clinical entity.

Use of diagnostics in wound management

Purpose of reviewWound healing research has progressed impressively over the past years. New insights into the pathogenesis of different chronic wounds and the study of novel treatment have made wound healing a model disorder and have revealed basic cellular and molecular mechanisms underlying chronic wounds. Although the observation is so obvious and simple, the interpretations by different observers can be quite variable. The interpretations of severity and change in severity by treatment may differ considerably between patient and practitioners. Recent findingsIn this review we provide comprehensive view on different aspects of wound diagnostic, including clinical measurement, new biomarkers in wound pathology, proteases evaluation, and future noninvasive sensor-based devices. SummaryWound caregivers are in the unique position of being able to observe the wound changes and describe these with knowledge and strict methodology, but also with the wide range of available wound diagnostic devices. The complexity of severity assessment in wound healing is reflected by the multiple clinical scores available. The best objective methods used to evaluate cutaneous tissue repair should have a high specificity and sensitivity and a low inter and intraobserver variation.

P63 is a helpful tool in the diagnosis of a primary cutaneous carcinosarcoma

To the Editor, Primary cutaneous carcinosarcoma (PCC) is an infrequently reported biphasic tumor composed of intimately admixed epithelial and mesenchymal components both of which must be malignant. It is exceedingly rare to arise primarily in the skin with less than 45 cases cited in the literature to date. The dual pattern of differentiation of closely intermingled epithelial and mesenchymal elements is highly suggestive for PCC. However, it may not be readily apparent on histologic examination because of poor differentiation of either part or unequal proportion of the two cell populations. Hence, in difficult cases, immunohistochemical studies can be helpful in elucidating that two distinct patterns of stromal differentiation exist. Herein, we contribute to the limited literature on cutaneous carcinosarcomas with a further case and accentuate on the diagnostic relevance of six staining tools, p63 and p53 particularly. An 85-year-old woman with a history of squamous cell carcinoma presented with a tender erythematous exophytic, centrally ulcerated mass 2 3 1 cm on the anterior scalp of several months duration. No history of trauma or radiation therapy in the area could be elicited. After histologic diagnosis, a wider excision was performed with no residual neoplasm reported on the microscopic evaluation of the entire resection. No recurrence of disease was detected on follow up. On histology, a biphasic tumor was appreciated (Fig. 1A) – nests of pleomorphic basaloid cells with peripheral palisading and a retraction artifact between epithelial nests and surrounding mucinrich stroma [a characteristic pattern found in basal cell carcinomas (BCCs)] were blended imperceptibly within a heterogenous sarcomatous stroma. The latter consisted of hypercellular, pleomorphic spindle cell proliferation, multinucleated giant cells and atypical mitoses (fibrosarcomatous pattern) (Fig. 1B). In addition, focally calcified osteoid, rimmed by malignant osteoblasts was appreciated (osteosarcomatous pattern). Immunohistochemical analysis showed the carcinomatous part to be positive for keratin, Ki-67, p53 and p63 and negative for S-100 and high-molecular weight caldesmon (HCD). Sarcomatous cells were strongly p53 positive, as well as slightly positive for keratin and Ki-67, but failed to label p63, S-100 and HCD. On the basis of a typical histomorphology and immunohistochemistry revealing dual differentiation, the tumor was referred to as a PCC: nodular type BCC and fibrosarcoma/osteosarcoma.

Histopathologic analysis of dermal lymphatic alterations in chronic venous insufficiency ulcers using D2-40

BACKGROUND Chronic venous insufficiency (CVI) ulcers represent a major medical problem worldwide. Current theories concerning the pathogenesis of CVI ulcers focus on abnormalities in the blood vascular system. Other abnormalities, such as chronic leg edema, may also play pathogenic roles in CVI ulcer development and further understanding of such alterations may lead to better treatments. OBJECTIVE To gain insight into lymphatic abnormalities occurring in CVI, we compared dermal lymphatics in histologic sections from CVI ulcers and normal controls. METHODS We compared global and architectural features of dermal lymphatics in D2-40-stained histologic sections from CVI ulcer tissue and from normal controls. D2-40 recognizes podoplanin, a transmembrane glycoprotein that is constitutively expressed in lymphatic endothelial cells, allowing us to distinguish dermal blood vessels from lymphatic vessels. RESULTS Our analyses reveal that CVI ulcer specimens have more dermal lymphatic vessels per unit area than controls (5.71 vs 4.08 per mm(2), respectively; P = .0281); a higher percentage of lymphatic vessels with collapsed lumina compared with controls (30.5% vs 8.1%, respectively; P < .0001); and a higher percentage of competent lymphatic vessels displaying open inter-endothelial junctions compared with controls (5.7% vs 2.9%, respectively; P < .0369). LIMITATIONS Our study is limited by its retrospective nature and relatively small sample size. CONCLUSIONS Lymphatic vessels in CVI ulcer specimens display global and architectural differences compared with lymphatic vessels in control specimens. These findings further implicate lymphatic dysfunction in the pathogenesis of CVI ulcers and allow for the formulation of a hypothesis concerning lymphatic changes that may be tested in future studies.

Primary localized cutaneous nodular amyloidosis associated with CREST (calcinosis, Raynaud's phenomenon, esophageal motility disorders, sclerodactyly, and telangiectasia) syndrome

and telangiectasia) syndrome Primary localized cutaneous amyloidosis (PLCA) is a rare condition that presents with the deposition of amyloid material in the skin, withno evidence of systemic involvement. Primary localized cutaneous nodular amyloidosis (PLCNA) is the rarest type of cutaneous amyloidosis. Of the three subdivisions of localized amyloidosis, macular and lichenoid subtypes show keratin-derived amyloid, whereas the nodular subtype is believed to be derived from plasma cells. Several disorders, including systemic sclerosis, primary biliary cirrhosis, systemic lupus erythematosus, Sjogren’s syndrome, and rheumatoid arthritis, have been associated with PLCA. Summers and Kendrick recently presented the first case of PLCNA with the CREST variant (calcinosis, Raynaud’s phenomenon, esophageal motility disorders, sclerodactyly, and telangiectasia) of systemic sclerosis. To our knowledge, we report the second case of this association. An 83-year-old woman presented with multiple, shiny, skin-colored nodules on the legs bilaterally that had been present for 25 years (Fig. 1a,b). The lesions had been asymptomatic and had recently begun to enlarge and develop several satellite nodules. Findings on physical examination revealed sclerodactyly, as well as a few scattered telangiectasias on the lips and pulp of the fingers. A biopsy specimen of the nodules showed diffuse eosinophilic aggregates of amorphous material in the superficial portion of the dermis, accentuated around vascular channels and adnexal structures (Fig. 2). Plasma cells within amyloid material were prominent. Congo red stain revealed an apple-green birefringence under polarized light. Deposits were positive for both Ak and Aj. Laboratory results showed a normal serum protein electrophoresis and a positive antinuclear antibody(ANA)withatiterof‡1:1280.ANAshowed an anticentromere antibody pattern, suggestive of the CREST variantof scleroderma. Based on the patient’s clinical, pathologic, and laboratory data, she was diagnosed with PLCNA and CREST syndrome. The amyloid fibrils in PLCNA consist of immunoglobulin light chains which are referred to as amyloid L (AL) type. These chains are produced by a clonal plasma cell population. This is in contrast with the amyloid A (AA) type which is associated with secondary amyloidosis and is derived from an acute-phase reactant secondary to long-standing inflammation. As the lesions in PLCNA may contain numerous plasma cells, they are best considered as isolated plasmacytomas. In conclusion, we believe that there is an association between PLCNA and the CREST variant of systemic sclerosis. First, PLCNA has been described in association with autoimmune connective tissue disorders. Second, association Figure 1 (a) Multiple, shiny, skin-colored nodules on the patient’s lower extremities. (b) Telangiectasias on the patient’s fingertips as a part of CREST (calcinosis, Raynaud’s phenomenon, esophageal motility disorders, sclerodactyly, and telangiectasia) syndrome

Allopurinol-induced palisaded neutrophilic and granulomatous dermatitis

We describe a 64-year-old man with past chronic myeloid leukemia. Palisading neutrophilic granulomatous dermatitis of the hands was diagnosed and related to recent allopurinol intake. Allopurinol is known to rarely cause granulomatous reactions, but this appears to be the first case of palisading neutrophilic granulomatous dermatitis induction. Possible mechanisms include immune complex deposition, an immune response directed against the metabolites of allopurinol, or allopurinol hypersensitivity exclusively localized to the skin.

Skin tightening of aging upper arms using an infrared light device.

BACKGROUND Upper arm skin laxity is an important area of cosmetic concern. Recent studies using a noninvasive infrared device has demonstrated its efficacy in tightening skin in various body regions. The use of this device in upper arm loose skin has not been investigated. OBJECTIVES To determine the safety and efficacy of an infrared device to treat upper arm laxity in aged skin. PATIENTS AND METHODS Twenty women with mild to very loose aged upper arm skin underwent two treatments with an infrared device 1 month apart. Nineteen patients completed the study with a 3‐month follow‐up. Outcome measures included investigator and participant evaluations of skin laxity improvement, blinded photographic assessments of skin tightening, and differences in circumferences and spectrophotometric analysis of collagen content in the treated arms. Two patients participated in histological evaluations. RESULTS The patient and investigator clinical assessments showed minimal improvement in skin laxity. There was a statistically significant decrease in arm circumference. Blinded photographic assessments and spectrophotometric analysis revealed no statistical improvement in skin laxity. The immediate post‐treatment histological evaluations showed architectural disarray of dermal collagen and elastin. CONCLUSION An infrared device is safe, well tolerated, and minimally effective in treating aged upper arm skin laxity. Cutera, Inc. donated the Titan Device used for this study

Pigmentary Deposition Disorders

Pigmentary deposition skin disorders are characterized by abnormal accumulation of pigmented substances that are of endogenous or exogenous derivation. Endogenous pigmentary deposition disorders are due to inherited diseases, mainly alkaptonuria (ochronosis). Exogenous pigmentary deposition disorders are due to drugs including antimalarials, phenothiazines, tetracyclines, amiodarone, clofazimine, chemotherapeutic agents, and hydroquinone (exogenous ochronosis) or heavy metals including silver, gold, mercury, arsenic, bismuth, and lead. Hyperpigmentation due to drugs is usually reversible with discontinuation of the therapy.

Alternately divided epidermal nevus of the fingers.

Abstract:  A 2‐year‐old white girl with divided (or kissing) epidermal nevus of the third and fourth fingers of the left hand is described. The possible pathogenesis of this unique lesion is also discussed.