Dermatomyositis panniculitis: a clinicopathological and immunohistochemical study of 18 cases.

BACKGROUND: Panniculitis occurring in dermatomyositis is uncommon, with only a few cases described in the literature, most of them as case reports. OBJECTIVE: This report describes the clinicopathological and immunohistochemical findings in a series of 18 patients with panniculitis associated with dermatomyositis. METHODS: In each patient, we collected the clinical data of the cutaneous lesions as well as the characteristic clinical and laboratory findings. A series of histopathologic findings was recorded in the biopsy of each patient. A panel of antibodies was used in some cases to investigate the immunophenotype of the infiltrate. Data of treatment and follow-up were also collected. RESULTS: Of the 18 patients, 13 were female and 5 were male, ranging in age from 13 to 74 years (median, 46.4 years). In addition to panniculitis, all patients presented pathognomonic cutaneous findings of DM and reported proximal muscle weakness prior to the diagnosis of panniculitis. Muscle biopsy was performed in 17 patients and MRI in one, all with the diagnosis of inflammatory myopathy. None of the patients presented any associated neoplasia. Panniculitis lesions were located in the upper or lower limbs. Histopathology showed a mostly lobular panniculitis with lymphocytes as the main component of the infiltrate. Most cases showed also numerous plasma cells and lymphocytes surrounding necrotic adipocytes (rimming) were frequently seen. Lymphocytic vasculitis and abundant mucin interstitially deposited between collagen bundles of the dermis were also frequent findings. Late-stage lesions showed hyaline necrosis of the fat lobule and calcification. Immunohistochemistry demonstrated that most lymphocytes of the infiltrate were T-helper lymphocytes, with some B lymphocytes in the lymphoid aggregates and small clusters of CD-123-positive plasmacytoid dendritic cells in the involved fat lobule. CONCLUSION: Panniculitis in dermatomyositis is rare. Histopathologic findings of panniculitis dermatomyositis are identical to those of lupus panniculitis. Therefore, the final diagnosis requires clinic-pathologic correlation.

Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version.

BACKGROUND: Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. OBJECTIVES: The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. METHODS: The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. RESULTS: Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. CONCLUSIONS: International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).

Definition of the features of acquired elastotic hemangioma reporting the clinical and histopathological characteristics of 14 patients.

BACKGROUND: During the last few years, new cutaneous vascular proliferations have been described, including a distinctive clinicopathologic variant of hemangioma, denominated acquired elastotic hemangioma. To date, there is only one series of six cases reported in the literature, thus, the clinical and morphological data of this variant are not well established. METHODS: Fourteen cases of acquired elastotic hemangioma were retrieved from the files of the Dermatopathology Unit at Wake Forest University School of Medicine. RESULTS: Acquired elastotic hemangioma affects sun-damaged skin of upper extremities and neck. Clinically, lesions present as slowly growing, painless, solitary, erythematous plaques. Histopathologically, they are characterized by a horizontal proliferation of capillary blood vessels in the upper reticular dermis in a background of solar elastosis. The vessels have plump endothelial cells that protrude into the vascular lumens in a 'hobnail' pattern. Of the 10 cases assessed by immunohistochemistry, 100% (10) expressed CD31 and CD34, 90% (9) expressed D2-40 and 10% (1) expressed SMA. CONCLUSION: Acquired elastotic hemangioma is a distinctive variant of hemangioma which should be differentiated from other cutaneous vascular tumors with a hobnail endothelial pattern, including angiosarcoma. The expression of D2-40 in most cases suggests a lymphatic origin of this acquired vascular proliferation.

Cutaneous myoepithelioma: an under-recognized cutaneous neoplasm composed of myoepithelial cells.

Benign and malignant neoplasms of myoepithelial cells comprise a rare but well-characterized group of tumors, among which myoepithelioma of the salivary glands is the best known. Extrasalivary examples of myoepithelioma also have been described in the breast, larynx, and retroperitoneum. Recently, myoepithelioma of the soft tissue also has been reported. According to this description, myoepithelioma and mixed tumors arising in the skin and subcutis represent points along a clinicopathologic spectrum of cutaneous and soft-tissue tumors. To the best of our knowledge, there has been only one case report of an entirely cutaneous myoepithelioma in the literature. We report herein five additional examples of purely myoepithelial tumors located exclusively in the dermis. Histopathologically, the neoplasms were well-circumscribed dermal lesions composed of fascicles of spindle cells with eosinophilic cytoplasm and ovoid-to spindle-shaped nuclei. Focally, neoplastic aggregations of more epithelioid cells representing large round cells with abundant pale cytoplasm arranged in solid clusters, cords, or strands were also seen. Ductal differentiation was not identified in either of these solid aggregations of epithelioid cells or in the fascicles of spindle-shaped cells. Nuclear pleomorphism in epithelioid and spindle-cell areas was mild, and mitotic figures were very sparse. In some cases, small, necrotic areas were seen within the solid aggregations of spindle-shaped cells. Neoplastic stroma was scant and composed of fibrillary collagen and abundant mucin. In one case, the stroma consisted of clusters of mature adipocytes intermingled with fascicles of myoepithelial cells. Areas of chondroid or osteoid metaplasia were not seen in any of the cases. Immunohistochemically, neoplastic cells expressed positivity for muscle specific actin (HHF35), alpha smooth muscle actin (IA4), S-100 protein, glial fibrillary acidic protein (GFAP), and epithelial membrane antigen (EMA), whereas stains for pan-cytokeratin (MNF116) were focal and weak. The findings in this report expand the clinical and histopathologic spectrum of cutaneous myoepithelioma, an under-recognized cutaneous neoplasm of myoepithelial cells.

Absence of Epstein-Barr virus in lymphomatoid papulosis. An immunohistochemical and in situ hybridization study.

BACKGROUND AND DESIGN: Lymphomatoid papulosis (LyP) and cutaneous Hodgkin's disease share many clinical, histopathologic, and immunohistochemical features. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of several lymphoid malignancies, including Hodgkin's disease. Given the similarities between LyP and Hodgkin's disease, we asked if EBV could be detected in lesions of LyP. We examined 31 specimens of LyP that were obtained from 24 patients for evidence of EBV by in situ hybridization to EBER1 transcripts and for immunohistochemistry of viral latent membrane protein 1 (LMP1). RESULTS: In no instance there was there any evidence of EBV gene products by either in situ hybridization or immunohistochemistry. CONCLUSIONS: The absence of EBV in LyP suggests that this virus is not operative in the pathogenesis of LyP. Furthermore, it suggests that LyP and Hodgkin's disease may not share the same molecular mechanisms despite their phenotypic similarities.

Multiple hereditary infundibulocystic basal cell carcinomas: a genodermatosis different from nevoid basal cell carcinoma syndrome.

BACKGROUND: Infundibulocystic basal cell carcinoma is a recently described distinctive clinicopathologic variant of basal cell carcinoma. Histopathologic differential diagnosis among infundibulocystic basal cell carcinoma, trichoepithelioma, and basaloid follicular hamartoma has generated controversy in the literature. OBSERVATIONS: Members of 2 families with multiple infundibulocystic basal cell carcinomas are described. Each patient showed multiple papular lesions, mostly located on the face. No patient showed palmar pits or jaw cysts. Forty-two cutaneous lesions from 5 patients were studied histopathologically. Thirty-nine lesions were infundibulocystic basal cell carcinomas. This clinicopathologic variant of basal cell carcinoma consists of a relatively well-circumscribed basaloid neoplasm composed of buds and cords of neoplastic cells arranged in anastomosing fashion and with scant stroma. Some of the neoplastic cords contain tiny infundibular cysts filled by cornified cells with abundant melanin. Linkage analysis in family 2 was performed using polymorphic markers (D9S196, D9S280, D9S287, and D9S180), and the affected members shared the same haplotype. Loss of heterozygosity analysis was performed in 2 affected members of this family from whom tumoral DNA was available, and although these individuals were constitutively heterozygous for D9S196, they did not show loss of heterozygosity for this marker in their neoplasms. CONCLUSIONS: Multiple hereditary infundibulocystic basal cell carcinomas represent a distinctive genodermatosis different from multiple hereditary trichoepitheliomas and nevoid basal cell carcinoma syndrome. We propose clinical and histopathologic criteria to distinguish infundibulocystic basal cell carcinoma from trichoepithelioma, basaloid follicular hamartoma, and folliculocentric basaloid proliferation.

Anaplastic carcinoma occurring in association with a mucinous cystic neoplasm of the pancreas.

Anaplastic carcinomas of the pancreas are considered variants of ductal adenocarcinoma. They typically occur in elderly men. They have rarely been reported to occur in association with mucinous cystic neoplasms of the pancreas. We report a case of anaplastic carcinoma occurring in association with a pancreatic mucinous cystic neoplasm, borderline-type, in a 25-year-old woman who presented with lymph node and hepatic metastases.

Adenosquamous carcinoma: a case report with immunohistochemical evaluation.

The histogenetic origin of adenosquamous carcinoma, a high-grade variant of malignant epithelial neoplasm, has long been debated. We report a case that clearly demonstrated a mucosal surface epithelial origin. This concept was supported through histologic analysis of hematoxylin- and eosin-stained sections, as well as by the pattern of immunohistochemical reactivity with antibodies directed against low and high molecular weight cytokeratins, cell adhesion molecules (CAM 5.2), and carcinoembryonic antigens. The histologic differential diagnosis, biological behavior, and prognosis of adenosquamous carcinoma are also examined.

Dental curettes: useful tools for obtaining nail material for mycologic examination.

Obtaining material, especially subungually, from suspected onychomycotic nails can be difficult and/or traumatic with instrumentation frequently utilized by dermatologists. Use of scalpel blades and standard dermal curettes is often awkward and/or traumatic to the nail bed. Large clippings require micronization with a nail mill or tedious processing with less specialized instruments prior to microscopic examination (potassium hydroxide preparation) and fungal culture. A mycologist at our institution has efficaciously utilized dental curettes to obtain powdery subungual material suitable for immediate mycological assessment. This nontraumatic technique is becoming increasingly popular among clinicians.

[Advances in molecular biology and their application in the diagnosis and treatment of melanoma]. / Novedades en biología molecular y su aplicación en el diagnóstico y el tratamiento del melanoma.

Even though malignant melanoma accounts for 4 % of all skin cancers, it is the type responsible for most deaths. The pathogenesis of melanoma is currently not well understood, although an interaction of environmental and genetic factors doubtlessly plays a role. Molecular biology in medicine has progressed increasingly rapidly in recent years. In dermatology, application of molecular biology techniques to the study of malignant melanoma has led to important advances in our knowledge of the main molecular pathways implicated in its development. These findings not only can improve our knowledge of the pathogenesis of the disease but may also have practical implications. Thus, molecular characterization of malignant melanoma may be of great help in differentiating between benign and malignant melanocytic lesions when histopathological features prove insufficient as is the case, for example, in Spitz nevus and spitzoid melanoma. In addition, knowledge of the abnormal molecular pathways in different malignant melanoma lesions can point to new therapeutic targets for treating patients with melanomas with distant metastases, in whom current chemotherapy has failed to extend life expectancy. At present, lack of availability is the main barrier to use of these techniques in dermatology--they are often limited to research, so not generally available in most hospitals. This problem will, however, be overcome when the molecular patterns become standardized, allowing a prognostic and therapeutic characterization of this important disease.

Anetodermic mycosis fungoides: a new clinicopathological variant of mycosis fungoides.

Mycosis fungoides is the most common type of primary cutaneous T-cell lymphoma. Several rare clinicopathological variants of mycosis fungoides have been described. Patients with these variants often also have classic mycosis fungoides at other sites of the body. Anetoderma is a cutaneous disorder in which multiple, oval lesions or atrophic plaques with wrinkled surface develop progressively due to loss of the dermal elastic tissue. Primary anetoderma occurs when there is no underlying associated disease and it arises on clinically normal skin, whereas secondary anetoderma appears in the same site as a previous specific skin lesion. There is a large list of heterogeneous dermatoses associated with secondary anetoderma. Two patients developed areas of secondary anetoderma on plaque stage lesions of mycosis fungoides. The lesions consisted of exophytic nodular lesions, with very soft consistency on palpation, scattered over the hyperpigmented plaques in one patient and violaceous indurated plaques with overlying epidermal atrophy and mild scale in the other. Histopathological study demonstrated that the cells involving the dermis were mainly T-helper lymphocytes, with few histiocytes and some multinucleate giant cells engulfing distorted elastic fibres. Elastic tissue stain demonstrated that elastic fibres were almost completely absent in the dermis of the anetodermic lesions. Anetodermic mycosis fungoides should be added to the list of clinicopathological variants of mycosis fungoides and mycosis fungoides should also be considered as a possible disease causing secondary anetoderma. Anetodermic mycosis fungoides shows clinical and histopathological features different from those of granulomatous slack skin.

Cutaneous vascular proliferation. Part II. Hyperplasias and benign neoplasms.

This second part of our review about vascular proliferations summarizes the clinicopathologic features of the cutaneous vascular hyperplasias and benign neoplasms. Hyperplasias comprise a heterogeneous group of vascular proliferations that eventually show a tendency to regression. Angiolymphoid hyperplasia with eosinophilia is included within the group of hyperplasias because of its historical denomination and its reactive nature, probably as a consequence of an arteriovenous shunt, although usually the lesions do not regress. Pyogenic granuloma, bacillary angiomatosis, intravascular papillary endothelial hyperplasia, and pseudo-Kaposi's sarcoma qualify as vascular hyperplasias because they regress when the stimulus that initiated them is removed. Benign neoplasms form a large group of hemangiomas with distinctive clinicopathologic characteristics, although some of them are of recent description and may produce diagnostic difficulties. We classified cutaneous benign vascular neoplasms according to their cell lineage of differentiation, for example, endothelial, glomus cell, and pericytic differentiation. Subsequent categories are established according to the size of the involved vessels (capillaries, venules and arterioles, or veins and arteries) or the nature of the proliferating vessels (blood or lymphatic vessels). Capillary and cavernous hemangiomas have been the terms classically used to name the most common variants of benign vascular neoplasms (i.e., infantile hemangiomas), but they are not the most appropriate denominations for these lesions. First, these names are not contrasting terms. Furthermore, most of the socalled "cavernous" hemangiomas are not hemangiomas (neoplasms) at all, but venous malformations. The most important conceptual issue is that, at any point in time, a particular hemangioma has its own histopathologic pattern throughout the depth of the lesion. For these reasons, we classified hemangiomas into superficial and deep categories. Some of the lesions reviewed have been recently described in the literature, and they may histopathologically mimic lesions of Kaposi's sarcoma; these include targetoid hemosiderotic hemangioma, microvenular hemangioma, tufted hemangioma, glomeruloid hemangioma, kaposiform hemangioendothelioma, spindle-cell hemangioendothelioma, and benign lymphangioendothelioma. In each of these lesions, we update and emphasize those clinical and histopathologic features that are helpful for differential diagnosis with lesions of authentic Kaposi's sarcoma in any of its three stages of development (patch, plaque, or nodule).

Cutaneous vascular proliferations. Part III. Malignant neoplasms, other cutaneous neoplasms with significant vascular component, and disorders erroneously considered as vascular neoplasms.

In this third and last part of our review of cutaneous vascular proliferations we include malignant vascular neoplasms and a group of heterogeneous cutaneous neoplasms characterized by a significant vascular component. We also review some disorders that, in our opinion, have been erroneously considered as vascular neoplasms. We review the epidemiologic, histogenetic, clinical, and histopathologic aspects of Kaposi's sarcoma in its four distinctive variants (classic, African-endemic, immunosuppressive drug-associated, and AIDS-associated Kaposi's sarcoma). There is still controversy about whether Kaposi's sarcoma represents a reactive vascular proliferation or a true neoplastic proliferation. In any event, most authors believe that Kaposi's sarcoma does not produce metastatic disease, but rather develops in multifocal fashion. However, Kaposi's sarcoma may cause death, especially in immunosuppressed patients. Epithelioid hemangioendothelioma, Dabska's tumor, and retiform hemangioendothelioma are examples of low-grade angiosarcoma. In contrast, cutaneous angiosarcomas, including the clinical variants of angiosarcoma of face and scalp in elderly patients, angiosarcoma associated with lymphedema, and radiation-induced angiosarcoma are highly aggressive neoplasms with poor prognosis and most patients die within a short period after presentation. A group of benign and relatively frequent cutaneous neoplasms, including multinucleate cell angiohistiocytoma, angiofibroma, angioleiomyoma, angiolipoma, cutaneous angiolipoleiomyoma, and cutaneous angiomyxoma are here covered because of their significant vascular component. Finally, we review briefly a series of cutaneous disorders that have been erroneously considered as vascular neoplasms. Kimura's disease is an inflammatory reactive condition of unknown origin, "benign" angioendotheliomatosis is a reactive intravascular proliferation of endothelial cells that occurs in the skin as a response to a variety of stimuli, "malignant" angioendotheliomatosis is an intravascular lymphoma, and acral pseudolymphomatous angiokeratoma of children (APACHE) is better interpreted as a pseudolymphoma.

Cutaneous vascular anomalies. Part I. Hamartomas, malformations, and dilation of preexisting vessels.

Classification of cutaneous vascular anomalies is difficult because conceptual confusion persists between vascular neoplasms and malformations. However, hemangiomas of the infancy fulfill criteria both for hyperplasia and neoplasm because they result from proliferation of endothelial cells, but often undergo complete regression. Despite these pitfalls we have classified cutaneous vascular anomalies into the following categories: hamartomas, malformations, dilatations of preexisting vessels, hyperplasias, benign neoplasms, and malignant neoplasms. In this first part of our clinicopathologic review of vascular anomalies, hamartomas, malformations, and dilatation of preexisting vessels are covered. Hamartomas include several combined vascular and melanocytic proliferations grouped as phakomatosis pigmentovascularis and the so-called eccrine angiomatous hamartoma that consists of proliferations of both eccrine glands and blood vessels. Vascular malformations result from anomalies of embryologic development, and in some of them the abnormalities of the involved vessels are more functional than anatomic, as is the case of nevus anemicus. In contrast, other cutaneous vascular malformations show striking morphologic abnormalities of the vascular structures. These anatomic vascular malformations are subdivided into the following groups: capillary, venous, arterial, lymphatic, and combined anomalies. Spider angioma, capillary aneurysm-venous lake, and telangiectases are not vascular proliferations at all, but dilations of preexisting vessels. In our opinion, most of the lesions described with the generic term of "angiokeratoma" are not authentic vascular neoplasms, but hyperkeratotic malformations of capillaries and venules or acquired telangiectases of preexisting blood vessels of the papillary dermis. Therefore the first group of these "angiokeratomas" are included in the vascular malformations section, and the second group are covered in the section of dilation of preexisting vessels. Lymphangiectases are considered the lymphatic counterpart of angiokeratomas because they result from ectasia of preexisting lymphatic vessels of the papillary dermis.

Neurofollicular hamartoma. A new histogenetic interpretation.

Neurofollicular hamartoma is a recently described entity characterized histopathologically by fascicles of spindle cells that are haphazardly arranged and laterally delimited by hyperplastic folliculo-sebaceous units. Immunohistochemical studies have shown the presence of a few S-100-positive cells scattered among the spindle cells. We report five cases of this peculiar entity and compare them to two examples of trichodiscomas. Both hamartomas were characterized by proliferations of spindle cells in close association with prominent folliculo-sebaceous units. Based on the clinical and histopathological findings, as well as the immunoperoxidase stains, we conclude that neurofollicular hamartomas are not different from trichodiscomas and fibrofolliculomas.