Calcinosis cutis: part I. Diagnostic pathway.

Calcinosis cutis is characterized by the deposition of insoluble calcium salts in the skin and subcutaneous tissue. The syndrome is separated into five subtypes: dystrophic calcification, metastatic calcification, idiopathic calcification, iatrogenic calcification, and calciphylaxis. Dystrophic calcification appears as a result of local tissue damage with normal calcium and phosphate levels in serum. Metastatic calcification is characterized by an abnormal calcium and/or phosphate metabolism, leading to the precipitation of calcium in cutaneous and subcutaneous tissue. Idiopathic calcification occurs without any underlying tissue damage or metabolic disorder. Skin calcification in iatrogenic calcinosis cutis is a side effect of therapy. Calciphylaxis presents with small vessel calcification mainly affecting blood vessels of the dermis or subcutaneous fat. Disturbances in calcium and phosphate metabolism and hyperparathyroidism can be observed.

Calcinosis cutis: part II. Treatment options.

Because calcinosis cutis is a rare syndrome, there is a notable lack of controlled clinical trials on its treatment. The efficacy of calcinosis treatment has only been reported in single cases or small case series. No treatment has been generally accepted as standard therapy, although various treatments have been reported to be beneficial, including warfarin, bisphosphonates, minocycline, ceftriaxone, diltiazem, aluminium hydroxide, probenecid, intralesional corticosteroids, intravenous immunoglobulin, curettage, surgical excision, carbon dioxide laser, and extracorporeal shock wave lithotripsy.

Solitary small- to medium-sized pleomorphic T-cell nodules of undetermined significance: clinical, histopathological, immunohistochemical and molecular analysis of 26 cases.

BACKGROUND: Solitary skin nodules composed of pleomorphic T lymphocytes are often the source of diagnostic problems. OBJECTIVE: To characterize the clinicopathological features, prognosis and optimal treatment modalities of patients with solitary lymphoid nodules of small- to medium-sized pleomorphic T lymphocytes. METHODS: Twenty-six patients were analysed for clinical, histopathological, immunophenotypical, molecular and follow-up data. RESULTS: Lesions were located mainly on the head and neck (n = 16; 61.5%) or trunk (n = 8; 30.8%). Histopathology showed non-epidermotropic nodular or diffuse infiltrates of small- to medium-sized pleomorphic T lymphocytes. Monoclonality was found by PCR in 54.2% of cases (n = 13/24). After a mean follow-up of 79.7 months, a local recurrence could be observed only in 1 patient. CONCLUSIONS: Our patients have a specific cutaneous lymphoproliferative disorder characterized by reproducible clinicopathological features. The incongruity between the indolent clinical course and the worrying histopathological features poses difficulties in classifying these cases unambiguously as benign or malignant. We suggest to describe these lesions as 'solitary small- to medium-sized pleomorphic T-cell nodules of undetermined significance'. Irrespective of the name given to these equivocal cutaneous lymphoid proliferations, follow-up data support a non-aggressive therapeutic strategy.

Podoplanin expression in fibrous histiocytomas and cellular neurothekeomas.

Podoplanin, also recognized by the monoclonal antibody D2-40, is a mucin-type transmembrane glycoprotein that is highly expressed in lymphatics and in a range of vascular and nonvascular proliferations. Recently, podoplanin has been detected in fibrous histiocytomas (FHs) and proposed to represent a potentially useful marker in the diagnostic evaluation of this lesion. There is, however, limited data concerning podoplanin expression in FH and its morphological mimics. Cellular neurothekeomas (CNs) are rare cutaneous neoplasms of uncertain histogenesis that often morphologically mimic FH. In this study, we reviewed our experience with podoplanin expression in FH (n = 30), especially in comparison to CN (n = 15). In addition, we also immunostained a selected group of other mesenchymal lesions that may fall within the differential diagnosis of FH for podoplanin, including dermal nerve sheath myxoma (n = 2), dermatofibrosarcoma protuberans (N = 8), and plexiform fibrohistiocytic tumor (n = 2). Podoplanin expression was observed in a significant subset of FHs (26/30, 86.6%) and in all CNs (15/15, 100%), whereas DFSPs, dermal nerve sheath myxomas, and plexiform fibrohistiocytic tumors were all negative. To the best of our knowledge, this is the first report demonstrating podoplanin expression in CN. Expression of podoplanin in CN represents a potential pitfall in the use of this antibody for diagnostic evaluation of FH. However, podoplanin may be of value as an adjunct to morphological examination in assessment of problematic lesions falling within the differential diagnosis of FH and CN.

Procollagen 1 and Melan-A expression in desmoplastic melanomas.

The histopathologic diagnosis of desmoplastic melanoma (DM) is usually based on typical conventional microscopic findings coupled with expression of S100 protein by neoplastic cells. Important differential diagnostic considerations include atypical fibroxanthoma (AFX) and spindle cell squamous carcinoma. Spindle cell squamous cell carcinoma is characterized by positivity for cytokeratin, whereas the diagnosis of AFX has been one of exclusion. Procollagen 1 (PC1) has been identified as a relatively sensitive marker of AFX. In this study, we sought to analyze the expression of PC1, S100 protein, and Melan-A in a series of 37 DMs (27 males and 10 females; ages 36-92 years, mean age 74 years). All lesions displayed a spindle cell morphology with varying degrees of desmoplasia. The neoplastic cells avidly expressed S100 protein in 37 of 37 neoplasms. A complete lack of PC1 expression was noted in 24 of 37 (64.9%). There was a weak PC1 expression by 9 DMs (24.3%) and a moderate expression by 4 DMs (10.8%). Melan-A expression was found in 19 of 37 DMs (51.4%), but in 10 lesions, the expression was only faint and focal. We conclude that PC1 labeling of DM is not uncommon but poses little risk for misdiagnosis, provided the stain is performed as part of panel that includes S100 protein. Melan-A offers little for the diagnosis of DM, as less than a quarter of lesions exhibit a strong reaction with this antibody. It is critical to employ a broad panel of antibodies, including S100 protein, Melan-A, cytokeratin, PC1, and others, in the immunohistochemical evaluation of spindle cell neoplasms of the skin.

Primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma: a cutaneous nodular proliferation of pleomorphic T lymphocytes of undetermined significance? A study of 136 cases.

Patients with skin nodules characterized by the infiltrate of pleomorphic small/medium T lymphocytes are currently classified as "primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma" (SMPTCL) or as T-cell pseudolymphoma. The distinction is often arbitrary, and patients with similar clinicopathologic features have been included in both groups. We studied 136 patients (male:female = 1:1; median age: 53 years, age range: 3-90 years) with cutaneous lesions that could be classified as small-/medium-sized pleomorphic T-cell lymphoma according to current diagnostic criteria. All but 3 patients presented with solitary nodules located mostly on the head and neck area (75%). Histopathologic features were characterized by nonepidermotropic, nodular, or diffuse infiltrates of small- to medium-sized pleomorphic T lymphocytes. A monoclonal rearrangement of the T-cell receptor-gamma gene was found in 60% of tested cases. Follow-up data available for 45 patients revealed that 41 of them were alive without lymphoma after a median time of 63 months (range: 1-357 months), whereas 4 were alive with cutaneous disease (range: 2-16 months). The incongruity between the indolent clinical course and the worrying histopathologic and molecular features poses difficulties in classifying these cases unambiguously as benign or malignant, and it may be better to refer to them with a descriptive term such as "cutaneous nodular proliferation of pleomorphic T lymphocytes of undetermined significance," rather than forcing them into one or the other category. On the other hand, irrespective of the name given to these equivocal cutaneous lymphoid proliferations, published data support a nonaggressive therapeutic strategy, particularly for patients presenting with solitary lesions.

Feasibility and diagnostic agreement in teledermatopathology using a virtual slide system.

We investigated the feasibility and diagnostic agreement of a virtual slide system (VSS) in teledermatopathology. Forty-six biopsy specimens from inflammatory skin diseases were selected and scanned with a VSS at the Research Unit of Teledermatology, Medical University of Graz, Graz, Austria. Images were stored on a virtual slide server on which a specific Web application suited for telepathology (http://telederm.org/research/dermatopath/) runs. Twelve teleconsultants from 6 different countries reviewed the 46 cases, working directly on the Web application. Telediagnoses agreed with gold standard and conventional diagnosis with an average of 73% and 74%, respectively. Complete concordance among all teleconsultants with gold standard and conventional diagnosis was found in 20% of the cases. In 10 cases in which complete clinical data were missing, the average agreement of telediagnosis with gold standard diagnosis and conventional diagnosis decreased to 65% and 66%, respectively. Only 3 of 4 cases of inflammatory skin diseases were correctly diagnosed remotely with VSS. The system that we have used, despite its usability, is not completely feasible for teledermatopathology of inflammatory skin disease. Moreover, the performance seems to have been influenced by the availability of complete clinical data and by the intrinsic difficulty of the pathology of inflammatory skin diseases.

Histopathologic features of cutaneous herpes virus infections (herpes simplex, herpes varicella/zoster): a broad spectrum of presentations with common pseudolymphomatous aspects.

Cutaneous eruptions caused by herpes simplex 1/2 (HSV-1/2) and herpes varicella/zoster (VZV) represent common dermatoses. In some cases, they present with atypical clinical and/or histopathologic features, including presence of dense lymphoid infiltrates with atypical lymphocytes simulating cutaneous lymphomas. In this study, we reviewed the biopsy specimens of 65 patients (33 males, 32 females; mean age, 61.2 years; median age, 62 years; age range, 19-96 years) with cutaneous eruptions caused by HSV-1/2 or VZV. Histologic examination revealed several atypical findings, including presence of dense lymphoid infiltrates, angiotropism, and atypical lymphocytes simulating malignant lymphoma. Immunohistochemistry performed in 22 cases showed a predominant T-cell infiltrate, in the majority of cases with variable numbers of CD30+ and CD56+ cells. Two cases with a pseudolymphomatous appearance and small clusters of CD30+ cells revealed a monoclonal population of T lymphocytes by PCR analysis, underlying the difficulties in classifying some of these cases correctly. Our study indicates that cutaneous herpes infections can exhibit several atypical histopathologic, immunohistochemical, and molecular features, and that in given cases accurate clinicopathologic correlation and short-term follow-up controls are necessary for differentiation from cutaneous lymphomas.

Confocal examination of untreated fresh specimens from basal cell carcinoma: implications for microscopically guided surgery.

OBJECTIVE: To evaluate the diagnostic accuracy of confocal examination of basal cell carcinoma (BCC) in microscopy-guided surgery. DESIGN: Four independent observers with no previous experience in confocal laser scanning (CLS) microscopy received standardized instruction about diagnostic CLS microscopic features. Subsequently, 120 confocal images of fresh excisions from BCCs or normal skin were evaluated by each observer, imaged using a commercially available, near-infrared, reflectance CLS microscope. Logistic regression analysis was performed on a combination of all morphologic features using the forward-stepwise (Wald) method. Reliability (interobserver agreement) data were evaluated by kappa statistic. SETTING: Department of Dermatology, Medical University of Graz. PATIENTS: Twenty patients with histologically verified BCC. INTERVENTIONS: Evaluation of fresh BCC excisions by CLS microscopy. MAIN OUTCOME MEASURES: Diagnostic accuracy of the method was evaluated by chi2 test. Diagnostic impact and reliability of each morphologic feature were evaluated by logistic regression analysis and kappa statistic, respectively. RESULTS: Overall, high diagnostic accuracy was achieved by the 4 observers. Logistic regression analysis revealed that mainly tumor cell nuclei and tumor nests should be taken into account for diagnostic decisions, whereas disintegration of tumor cells, peripheral palisading, and retraction of stroma were rarely useful. However, most of the features were highly reliable. CONCLUSIONS: This diagnostic validation study of CLS microscopy in microscopy-guided surgery yielded promising results and opens avenues for further studies. In the future, CLS microscopy may guide microsurgery of any skin cancer.

Acrodermatitis chronica atrophicans in a 15-year-old girl misdiagnosed as venous insufficiency for 6 years.

Acrodermatitis chronica atrophicans, the characteristic cutaneous manifestation of late Lyme borreliosis, typically occurs in elderly women. To our knowledge, only 4 cases of acrodermatitis chronica atrophicans in children have been described. Prompt diagnosis and treatment are important to prevent progression of disease and extracutaneous complications. We describe a 15-year-old girl with acrodermatitis chronica atrophicans of the left leg that had been misdiagnosed as chronic venous insufficiency for 6 years. Because of the long-standing disease course, skin changes expanded and progressed to marked atrophy. The correct diagnosis was finally based on clinical, histopathologic, and serologic findings. The girl was treated with oral doxycycline for 6 weeks, but her skin changes did not fully normalize. This case illustrates the possibility of acrodermatitis chronica atrophicans appearing in childhood and the difficulties in differentiating vascular disorders from acrodermatitis chronica atrophicans on the basis of the clinical appearance alone.

Pitfalls in the clinical and dermoscopic diagnosis of pigmented actinic keratosis.

Pigmented actinic keratosis and melanoma may exhibit overlapping clinical features, thus representing a diagnostic challenge for dermatologists. Although the differentiation between these two entities is traditionally done by histopathology, dermoscopy has been utilized as a useful additional aid for improving the clinical diagnostic accuracy of such pigmented skin lesions. We report the clinical and dermoscopic features of two pigmented actinic keratoses to discuss the difficulties in their preoperative differential diagnosis.

Cutaneous lymphomas with prominent granulomatous reaction: a potential pitfall in the histopathologic diagnosis of cutaneous T- and B-cell lymphomas.

The presence of a granulomatous reaction in lesions of cutaneous lymphomas has been described in the past in several cases. Especially in mycosis fungoides, a "granulomatous" variant of the disease has been well characterized. We studied the clinicopathologic features of cutaneous lymphomas with prominent granulomatous reaction, including both cutaneous T-cell lymphomas and B-cell lymphomas (primary cutaneous lymphoma 22, secondary cutaneous lymphoma one). Biopsies of 23 patients with histopathologic features of cutaneous T-cell lymphoma or cutaneous B-cell lymphoma with prominent granulomatous reaction were included in this study. A prominent granulomatous reaction was defined as the presence of a granulomatous component exceeding 25% of the dermal infiltrate. There were 14 cases of mycosis fungoides, two of subcutaneous panniculitis-like T-cell lymphoma, four of small/medium pleomorphic T-cell lymphoma, one of follicle center cell lymphoma, one of large B-cell lymphoma, and one of secondary cutaneous peripheral T-cell lymphoma. Altogether, a prominent granulomatous reaction could be observed in 1.8% of all patients with cutaneous lymphoma (primary or secondary) registered in the files of the Department of Dermatology of the University of Graz (Graz, Austria), demonstrating that there is a distinct, albeit small, proportion of cases revealing this peculiar reaction pattern. In seven cases a misdiagnosis of granulomatous dermatitis preceded the correct diagnosis for a period of 1-216 months, suggesting that sequential biopsies and complete phenotypic and molecular genetic analyses should be carried out in cases of "unusual" granulomatous dermatitis.

Dermoscopic features of melanoma on the scalp.

There is a need to improve the early detection of melanoma of the scalp because it is characterized by a poorer prognosis compared with melanoma on other body sites. Dermoscopy is a useful tool for the early detection of melanoma but no previous reports on dermoscopic features of scalp melanoma have been published. We describe the first case of melanoma of the scalp seen by dermoscopy exhibiting a multicomponent global pattern with atypical pigment network, irregular streaks, and regression structures. In contrast to the dermoscopic features usually seen in melanoma occurring on the face, the same morphologic type of pigment network usually seen in melanoma of the trunk was observed in our case of scalp melanoma.