Skin-infiltrating T cells display distinct inflammatory signatures in lichen planus, bullous pemphigoid and pemphigus vulgaris.

Introduction: We here thought to dissect the inflammatory signature in lesions of three skin disorders, which show a common adaptive immune response against autoantigens of the skin but are characterized by diverging clinical phenotypes. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are type-2-dependent, IgG autoantibody-driven blistering disorders of mucous membranes and skin, which target desmoglein (Dsg)3 and bullous pemphigoid (BP)180, respectively. In contrast, lichen planus (LP) is a common chronic inflammatory disease of the skin and mucous membranes with a pronounced dermal T cell infiltrate. We previously identified peripheral type 1 and 17 T cell responses against Dsg3 and BP180 in a cohort of LP patients strongly suggesting that the underlying inflammatory T cell signature may drive the evolving phenotype. Methods: Paraffin-embedded skin biopsies from well-characterized patients with LP (n=31), BP (n=19), PV (n=9), and pemphigus foliaceus (PF) (n=2) were analysed. Areas with the most prominent inflammatory infiltrate were excised with punch biopsies and tissue microarrays (TMA) containing multiple biopsies were created. Using multicolor immunofluorescence, the inflammatory infiltrate was stained with antibodies against multiple cellular markers, i. e. CD3ϵ, CD4, CD15, TCR-δ, the cytokine IL-17A, and the transcription factors, T-bet and GATA-3. Results: In LP, there was a higher number of CD4+ T cells expressing T-bet compared to GATA-3. In contrast, CD4+ T cells in PV and BP skin lesions more frequently expressed GATA-3 than T-bet. IL-17A+ cells and IL-17A+ T cells were found to a similar extent in all the three disorders. IL-17A+ granulocytes were more predominant in BP than in LP or PV. Of note, the majority of IL-17A+ cells in LP were neither T cells nor granulocytes. Discussion: Our findings in inflammatory skin infiltrates clearly show a predominant type 1 signature in LP in contrast to a preponderance of type 2 T cells in PV and BP. In contrast to LP, granulocytes and to a much lesser extent CD3+ T cells were a cellular source of IL-17A in BP and PV. These data strongly suggest that different inflammatory cell signatures drive evolving clinically diverse phenotypes of LP, PV and BP despite common target antigens of the skin.

Histopathological features of human mpox: Report of two cases and review of the literature.

Human monkeypox is an emerging zoonosis with epidemic potential. Although it usually causes a mild disease, some patients are at risk for complications, including death. In face of the current outbreak of monkeypox in non-endemic areas, awareness is paramount to diagnose it timely, prompting an early break of the transmission chain. Histopathologic findings in vesiculopustular lesions of monkeypox are distinctive, consisting of ballooning and reticular degeneration of keratinocytes, necrosis, especially of the upper portions of the epithelium, multinucleation of keratinocytes, nuclear enlargement showing a "basophilic halo" around a "ground glass" eosinophilic center, the orthopoxvirus-specific cytoplasmic eosinophilic Guarnieri-type inclusions (in the pustular stage especially), and a dense mixed inflammatory cell infiltrate with prominent neutrophil exocytosis. The diagnosis of human monkeypox requires a high index of suspicion. In correlation with clinical information, histopathological findings allow for a presumptive diagnosis of monkeypox if polymerase chain reaction testing is not available. Both clinicians and pathologists can optimize diagnostic sensitivity, respectively, by considering the epidemiological context, sampling pustular lesions and providing data for clinicopathological correlation, and by intentionally searching the tell-tale eosinophilic inclusions in genital, anal and oral lesions with reticular and ballooning degenerescence.

Lichenoid exanthema mimicking graft-versus-host disease associated with obstructive lung disease in a non-transplanted patient.

Lichenoid graft-versus-host disease (GVHD) is commonly observed in patients who have received donor lymphocyte infusions or allogeneic bone marrow transplantation (BMT). Here we report a striking case of lichenoid GVH-like exanthema in a young woman without any history of blood transfusions or BMT. A polymorphous, multiforme-like exanthema was observed after systemic antibiotic therapy of bronchitis and was initially diagnosed as drug eruption. Later on, disseminated lichenoid papules were noticed on the trunk and extremities with all histologic and clinical characteristics of lichenoid GVHD. Cutaneous GVH-like disease developed, as did obstructive lung disease. Pulmonary as well as skin disease were both refractory to various immunosuppressive therapies. The immune pathogenesis that caused the skin and lung disease in this patient remains unclear. Multiple pregnancies with two abortions with the potential induction of microchimerism may play a role in the disease pathogenesis.

Tumor of follicular infundibulum is Basal cell carcinoma.

Tumor of follicular infundibulum (TFI) is currently thought to be a benign epithelial neoplasm with follicular differentiation. It is encountered commonly in association with basal cell carcinoma (BCC), often as an incidental finding. We reexamined 24 cases of TFI and noted, often only focally, many changes typical of BCC, including palisading of cells at the periphery of aggregations, germinative cells, follicular germs in the absence of a follicular papilla, crowding of cells, individual necrotic neoplastic cells, fibromucinous stroma, and clefts between aggregations of neoplastic cells and stroma. Five cases were associated with BCC, and 2 of them showed obvious continuity between both types of lesions. Moreover, we observed recurrences of what seemed to be a completely removed BCC in which tiny columns of cells typical of TFI were present in surgical margins. Those findings prompted us to conclude that TFI may be one of many manifestations of BCC rather than a differential diagnosis of it.

Genital Paget's disease in a man.

Pagetoid cells are large intraepidermal cells which spread intraepidermally. We report a 67-year old Caucasian male, who presented for the first time in 1993 with a long-standing pruritic lesion at the scrotum. He was treated for several years by antiinflammatory ointments. Only in July 2003 was a biopsy taken for the first time. The histopathological evaluation revealed the diagnosis of an extramammary Paget's disease (EMPD). Pagetoid cells are large intraepidermal cells with a large nucleus and ample cytoplasm. EMPD consists of primary malignant cells of epidermal origin, but in rare cases, pagetoid cells may also originate from carcinomas with epidermotropic growth. EMPD is a slowly progressing disease, but invading and metastasing tumors may also develop. Considering the good prognosis with long-term survival, nonsurgical modalities should be considered as primary treatment for noninvasive EMPD.

Nevus psiloliparus: report of two nonsyndromic cases.

A diagnosis of nevus psiloliparus was made both clinically and histopathologically in two otherwise healthy girls, one being 4 years and the other one being 1 year old. A congenital hairless patch with a round or oblong shape and a soft surface was noted on the scalp. In one case the lesion was yellowish and flat, whereas in the other case it was skin colored and somewhat elevated. In both cases, histopathological examination showed the absence of mature hair follicles and the presence of undeveloped follicular structures as well as orphaned arrector pili muscles in the dermis. As a new histopathological feature of this type of nevus, we found arrested anlagen of hair bulbs in both cases. The fatty tissue was abundant and also involved, in the form of aberrant lobules, the lower portion of the dermis. Clinical examination did not show any associated extracutaneous abnormality, and during a follow-up period of 2 years in either case, respectively, the children developed without any complication. Although neurological abnormalities could not be excluded by imaging techniques, such extracutaneous involvement is highly unlikely because the nevi psilolipari were of rather limited size. When clinicians and dermatohistopathologists have become familiar with this new entity, they will most likely recognize it as a nonsyndromic skin disorder more often than as a cutaneous sign of encephalocraniocutaneous lipomatosis.