Metastasizing soft tissue tumor of light damaged skin: atypical fibroxanthoma or malignant fibrous histiocytoma?

A 86-year-old female patient presented with a ca. walnut-sized, centrally ulcerated preauricular tumor on the right side as well as a firm submandibular lymph node. Histology disclosed a soft-tissue tumor breaking into the lymph node consisting partly of fibroblast-like and partly of histiocyte-like cells. Clinical and histological criteria speak for both an atypical fibroxanthoma (AFX) as well as a malignant fibrous histiocytoma (MFH). A differentiation into two entities does not appear appropriate in our opinion. As the term "AFX" is classified as a benign tumor, "metastasizing AFX" (mAFX) should be considered a special form of MFH or be diagnosed as such, respectively.     

Histiocytic sarcoma with secondary involvement of the skin and expression of CD1a: evidence of indeterminate cell differentiation?

BACKGROUND: Histiocytic sarcoma is an exceedingly rare malignant neoplasm composed of cells with a monocyte/macrophage phenotype. In the current nosology of histiocytic neoplasms, histiocytic sarcoma is separate from indeterminate cell histiocytosis, a generally benign disorder characterized by proliferation of a CD1a+ and S-100+ population of cells lacking Birbeck granules usually limited to the skin. METHODS: We present a case of histiocytic sarcoma in a 64-year-old man presenting as a peritonsillar mass and secondarily involving the skin. RESULTS: The malignant cells in the extracutaneous foci of disease expressed macrophage-associated antigens including S-100 but were CD1a-. The malignant cells in the skin coexpressed CD1a and S-100 but lacked ultrastructural features of Langerhans cells, findings indicative of indeterminate cells. CONCLUSIONS: We discuss the clinical and histopathologic differential diagnosis in association with prior reported cases of histiocytic sarcoma, particularly in cases involving the skin and cases expressing the Langerhans cell-associated antigen CD1a.     

Panfollicular carcinoma or trichoblastic carcinoma with panfollicular differentiation?

Herein, we report two cases of a follicular neoplasm with panfollicular differentiation showing architectural and cytologic findings suggestive of a malignancy. Immunohistochemical analysis of β‐catenin expression in the neoplasm showed nuclear and cytoplasmic immunoreactivity, with no reactivity in the transitional and shadow cells, consistent with β‐catenin expression of pilomatrical tumors. Staining for BerEp4 was positive at the periphery of both neoplasms, suggesting germinative differentiation of the neoplastic cells, whereas staining for the follicular stem‐cell marker PHLDA‐1 (TDAG51) showed strong focal expression in the tumor cells of both cases. Given these findings, these neoplasms show features of both panfollicular neoplasms and basal cell carcinoma with panfollicular/matrical differentiation. These are the first cases of this neoplasm reported to date. More reports are needed to assess their malignant potential.     

Regulatory and effector B cells: Friends or foes?

B cells have moved to the center stage in many autoimmune diseases including autoantibody-mediated diseases and T cell-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. B cells play an important role for immune response beyond antibody production through mechanisms like antigen presentation and cytokine production. However, not all B cells positively regulate immune responses. Regulatory B cells negatively regulate immune responses by production of anti-inflammatory cytokines such as IL-10, IL-35, and TGF-β. Regulatory B cells have been found to be decreased and/or functionally impaired in various autoimmune diseases. In contrast, B cells also produce pro-inflammatory cytokines, such as IL-6, IFN-γ and GM?­?CSF. These effector B cells contribute to the pathogenesis of autoimmune diseases. Regulatory and effector B cell balance regulates immune response through the release of cytokines. Furthermore, a protocol that selectively depletes effector B cells while sparing regulatory B cells would represent a potent therapy for autoimmune diseases rather than pan-B cell depletion using anti-CD20 mAb.     

Merkel cell tumor in a trichilemmal cyst: collision or association?

An 86-year-old white male presented with an erythematous, painless, slowly growing, and firm left thigh nodule. Histologic examination revealed a dermal proliferation of monomorphous cells arranged in trabeculae, nests, and sheets with an infiltrative growth pattern. The cells had a high nuclear-cytoplasmic ratio, finely granular nuclear chromatin, and nuclear molding. Numerous mitotic figures, apoptotic cells, and individual cell necrosis were present; lymphovascular invasion was identified. The tumor was attached, demonstrating pagetoid intraepithelial migration, to a follicular cyst lined by squamous epithelium, lacking a granular cell layer and filled with compact keratinous content, diagnostic of trichilemmal cyst. Immunohistochemical study revealed that tumor cells expressed pan-cytokeratin (CK), chromogranin, synaptophysin, neuron-specific enolase, and CK20 (dotlike staining pattern), thus supporting the diagnosis of Merkel cell carcinoma. The association of Merkel cell carcinoma with a cyst is an exceptionally rare occurrence. As a result of the prominent involvement of the cyst wall by tumor cells, we favor that in this case carcinoma arose in the trichilemmal cyst rather than being a collision tumor. This hypothesis is also supported by the recent observation that Merkel cells are frequently present within normal hair follicles, especially in the isthmic portion that corresponds with the area of origin of the trichilemmal cyst.     

Nitric oxide,skin growth and differentiation: more questions than answers?

Nitric oxide has varied effects on the skin. In this review the role of nitric oxide in cutaneous wound healing, apoptosis, carcinogenesis and psoriasis is discussed.     

Bednár tumor associated with dermal melanocytosis: melanocytic colonization or neuroectodermal multidirectional differentiation?

BACKGROUND: Neuroectodermal differentiation or melanocytic colonization are the opposing theories of histogenesis for the Bednár tumor or pigmented dermatofibrosarcoma protuberans (DFSP). OBSERVATION: A 31-year-old African-American woman presented with a 2-cm blue-black shoulder nodule of 1-year duration. Punch biopsy revealed a CD34+, Factor XIIIa-DFSP, harboring numerous, pigmented spindle S100+, Mart-1+ and HMB-45+ cells. Subsequent wide excision demonstrated pigmented dendritic and spindled cells widely scattered throughout the dermis of the 3-cm excisional margins and punch biopsy specimens of normal skin from both shoulders. This latter process was interpreted as dermal melanocytosis (nevus of Ito). The dermal pigmented spindle cells were Mart-1+ and CD34-, and were associated with non-pigmented CD34+, cytologically banal spindle cells, which were more numerous in the excisional margins than the contralateral shoulder. CONCLUSION: Reported herein is a singular case of Bednár tumor associated with dermal melanocytosis. Although the coexistence of these processes implicates colonization of the DFSP by constituent dermal melanocytes, the mixed immunophenotype (CD34+ or Mart-1+ cells) of dispersed dermal spindle cells hints at the possibility of a common cell of origin: the putative neuromesenchymal cell. In effect, the Bednár tumor could represent one part of a spectrum of neural crest-derived dermal tumors that includes dermal melanocytosis, cellular blue nevus and conventional DFSP.     

What is really in control of skin immunity: lymphocytes,dendritic cells,or keratinocytes? facts and controversies

The pathophysiology of atopic dermatitis is still under discussion. Although it is widely accepted that environmental factors and a genetic predisposition are essential, the role of the innate and adaptive immune system and the functional cascade of the cells involved is still unclear. A concept that integrates all immune cells as equally essential has allure. In addition, barrier abnormalities due to mutations of the gene coding for filaggrin and down-regulation of antimicrobial peptides, such as LL-37 and β-defensins 2 and 3, were very recently found to be relevant for the pathogenesis of atopic dermatitis.     

Onychomycosis with onychodystrophy or acrolentiginous melanoma with onychomycosis and onychodystrophy?

A 68-year-old female patient had been treated locally and systemically for onychomycosis of the left thumbnail for 1 year. During the course of treatment there was increasing destruction of approximately 50% of the nail without Hutchinson's sign. Dermoscopically there were yellow to brown vertical stripes of varying width in the remaining parts of the nail. In the visible nail matrix reddish, brownish and grey-black colored components with varying differential structures could be detected. An acrolentiginous melanoma with a diameter of 1.04?mm could be identified histologically and the associated onychomycosis was confirmed by culturing.     

Systemic lupus erythematosus or infection with HIV,or both?

The features of both HIV infection and connective tissue disease are often nonspecific and may mimic other disorders as well as each other. We treated a patient with presumed systemic lupus erythematosus (SLE) for 4 years, who finally admitted to longstanding infection with HIV. The coexistence of SLE and HIV is unusual and has, although reported in the rheumatological journals, not often been discussed in the dermatological literature.     

Beyond antibodies: B cells in Hidradenitis Suppurativa: Bystanders,contributors or therapeutic targets?

Hidradenitis Suppurativa (HS) is a chronic inflammatory dermatosis in which B cells play a prominent but unclear role. Our understanding of the role of B cells in innate and adaptive immunity (including antibody production, antigen presentation and effector functions) is rapidly evolving; and these novel findings require integration into the pathophysiologic model of HS. B cells are transiently present in normal human skin and have functions in the maintenance of innate cutaneous immunity. Recruitment and trafficking of B cells in significant numbers to skin is mediated via B cell-specific chemokines as well as shared signalling with T-cells. The evidence suggests that the presence of antibody-secreting B cells is not sufficient to induce clinical disease and T-cell interaction is required to induce clinical disease. Such interactions can occur in secondary lymphoid organs adjacent to involved tissue or in tertiary lymphoid organs which develop in response to the HS inflammatory milieu. This milieu directly mediates the types of antibodies produced by B cells, given the role of cytokines in B-cell class switching. Identified antibodies in HS (IgG, IgM, ASCA, ACPA) currently demonstrate no evidence of pathogenicity, but may be novel biomarkers for disease severity. B cells also have anti-inflammatory properties through production of IL-10 and IL-35 which require experimental validation. Overall, B cells in HS are likely to be involved in amplification of a pre-existing inflammatory response; but it remains unclear whether they may be directly pathogenic.     

Tight junctions and differentiation – a chicken or the egg question?

Skin barrier function is indispensable to prevent the uncontrolled loss of water and solutes and to protect the body from external assaults. To fulfil this function, keratinocytes undergo a complex pathway of differentiation that terminates in the formation of the stratum corneum. Additionally, tight junctions (TJs), which are cell-cell junctions localized in the stratum granulosum, are involved in the barrier function of the skin. Important biological and clinical roles of TJs are strongly suggested by altered TJ protein levels and distribution in skin diseases like psoriasis, ichthyosis and atopic dermatitis. Because these skin diseases show alterations in differentiation and TJs, it was suggested that changes in TJs might simply be a consequence of altered differentiation. However, in this viewpoint, we like to argue that the situation is not as simple and depends on the specific microenvironment. We discuss three hypotheses regarding the interplay between TJs/TJ proteins and differentiation: (1) TJs/TJ proteins are influenced by differentiation, (2) differentiation is influenced by TJs/TJ proteins, and (3) TJs/TJ proteins and differentiation are independent of each other. In addition, the concept is introduced that both processes are going on at the same time, which means that while one specific TJ protein/barrier component might be influenced by differentiation, the other may influence differentiation.     

Psoriasis: Psychosomatic,somatopsychic, or both?

Psoriasis is a chronic inflammatory disorder characterized by substantial psychiatric comorbidity. Historically, anecdotal observations have suggested that psychosocial distress can trigger flares of psoriasis, but over the past several decades, high-quality data from experimental studies support the assertion that stress plays a critical role in the pathogenesis of psoriasis. There may be a subset of patients unable to elicit an appropriate immunosuppressive response to stress through upregulation of cortisol, with resultant exacerbation of their psoriasis. Other notable studies revealed that key neuromodulators, including substance P, calcitonin gene–related peptide, vasoactive intestinal peptide, and nerve growth factor may be potent regulators of neurogenic inflammation that induce psoriasis flares through a stress-mediated mechanism. Preliminary trials in humans that examine psychosocial interventions to reduce stress, as well as animal studies targeting specific neuropeptides, provide support for the concept that alteration of pathways mediated by the stress response represents novel forms of therapy in the management of psoriasis.