Site-specific immunophenotyping of keloid disease demonstrates immune upregulation and the presence of lymphoid aggregates.

BACKGROUND: Keloid disease (KD) is a common fibroproliferative disorder of unknown aetiology. T cells and macrophages are increased in KD and are thought to contribute to its pathogenesis. However, while a link between inflammation and fibrotic disorders is well known for other disorders, it remains undetermined in KD. OBJECTIVES: Systematically to immunophenotype the inflammatory infiltrate of KD in situ in a site-specific manner, and to compare this with normal skin and scar tissue. METHODS: Sixty-eight keloid cases were screened for the presence of all three (intralesional, perilesional and extralesional) keloid-associated specific tissue sites. Subsequently, a complete set of 25 keloid biopsies (from different patients) was compared with normal skin (n = 11) and normal scar (n = 11) samples and subjected to systematic, site-specific quantitative immunohistomorphometry and histochemistry, using a range of immunological markers of B cells, T cells, macrophages, mast cells (MCs) and Langerhans cells. RESULTS: T cells, B cells, degranulated and mature MCs (coexpressing OX40 ligand) and alternative macrophages (M2) were all significantly increased in intralesional and perilesional KD sites compared with normal skin and scar tissue (P < 0·05). Additionally, 10 of 68 KD cases (15%) showed the presence of distinctive lymphoid aggregates, which resembled mucosa-associated lymphoid tissue (MALT). CONCLUSIONS: The increased number and activity of MCs and M2 may implicate inflammation in the fibrotic process in KD. The distinct KD-associated lymphoid aggregate resembles MALT, for which we propose the term 'keloid-associated lymphoid tissue' (KALT). It may perpetuate inflammatory stimuli that promote KD growth. KALT, MCs and M2 are promising novel targets for future KD therapy.

Lichen planopilaris following hair transplantation and face-lift surgery.

Cosmetic surgical procedures, including hair transplantation and face-lift surgery, are becoming increasingly popular. However, there is very little information regarding the associated development of dermatological conditions following these procedures. Lichen planopilaris (LPP) is an uncommon inflammatory hair disorder of unknown aetiology that results in permanent alopecia and replacement of hair follicles with scar-like fibrous tissue. Frontal fibrosing alopecia (FFA), a variant of LPP, involves the frontal hairline and shares similar histological findings with those of LPP. We report 10 patients who developed LPP/FFA following cosmetic scalp surgery. Seven patients developed LPP following hair transplantation, and three patients developed FFA following face-lift surgery. In all cases there was no previous history of LPP or FFA. There is currently a lack of evidence to link the procedures of hair transplantation and cosmetic face-lift surgery to LPP and FFA, respectively. This is the first case series to describe this connection and to postulate the possible pathological processes underlying the clinical observation. Explanations include Koebner phenomenon induced by surgical trauma, an autoimmune process targeting an (as yet, unknown) hair follicle antigen liberated during surgery or perhaps a postsurgery proinflammatory milieu inducing hair follicle immune privilege collapse and follicular damage in susceptible individuals.

Does collapse of immune privilege in the hair-follicle bulge play a role in the pathogenesis of primary cicatricial alopecia?

BACKGROUND: The hair-follicle bulge has recently been added to a growing list of human tissue compartments that exhibit a complex combination of immunosuppressive mechanisms, termed immune privilege (IP), which seem to restrict immune-mediated injury in specific locations. As epithelial hair-follicle stem cells (eHFSC) reside in the hair-follicle bulge region, it is conceivable that these IP mechanisms protect this vital compartment from immune-mediated damage, thereby ensuring the ongoing growth and cyclic regeneration of the hair follicle. Primary cicatricial alopecias (PCA) are a group of inflammatory hair disorders that result in hair-follicle destruction and permanent alopecia. Growing evidence suggests that eHFSC destruction is a key factor in the permanent follicle loss seen in these conditions. AIM: To explore the possible role of bulge IP collapse in PCA pathogenesis. METHODS: We report three clinically distinct cases of PCA. Immunohistochemical analyses of paired biopsies from lesional and uninvolved scalp skin were compared using recognized markers of IP. RESULTS: Immunohistochemical investigation found increased expression of major histocompatibility complex (MHC) classes I and II and of beta2-microglobulin in the bulge region of lesional follicles compared with uninvolved follicles in each case. Further, expression of the bulge marker keratin 15 was reduced in lesional skin in two of the cases. CONCLUSIONS: This small series represents our first preliminary attempts to ascertain whether bulge IP collapse may play a role in PCA pathogenesis. We present standard parameters relating to hair-follicle IP in the bulge region of three patients with distinct PCA variants, and show the presence of features consistent with bulge IP collapse in each case.

Can keratinocytes cause failure of osseointegration?

AIM: Bone-anchored hearing aids are well established, implanted devices. We present two patients who suffered mixed hearing loss and who underwent titanium implant placement in the temporal bone to enable attachment of bone-anchored hearing aids. Osseointegration is necessary for such implants to function. We report these two cases to highlight how such osseointegration may be disrupted. METHOD: Attached tissue from the explanted or removed titanium implants was examined by transmission electron microscopy and histopathological analysis. RESULTS: Attached tissue from both implants showed the presence of keratinocytes at the titanium implant and living bone interface. This was confirmed by histopathological analysis. In one case, there was frank keratinocyte proliferation, which had led to osseointegration failure; in the other case, such proliferation was present but not so advanced. CONCLUSION: These findings suggest that, in the cases reported, keratinocytes implanted between the titanium and the living bone, leading to disruption of osseointegration.

Dermal non-neural granular cell tumour (so-called primitive polypoid granular cell tumour): a distinctive entity further delineated in a clinicopathological study of 11 cases.

AIMS: Cutaneous and soft tissue granular cell tumour is a well-characterized benign neoplasm of neural origin. However, there remains a subcategory of granular cell tumour, first described by Le Boit as 'primitive polypoid granular cell tumour', that shows no obvious line of differentiation. The aim of this study is to further the characterization of this lesion by undertaking a clinicopathological review. METHODS AND RESULTS: Eleven cases of dermal non-neural granular cell tumour were retrieved from one of the authors referral archives (E.C.) and both the histology and immunohistochemistry reviewed. Clinical data with follow-up were obtained from the referring pathologists. The lesions most commonly occurred in young to middle-aged adults (nine cases, median = 33 years, age range 6-56 years), with a slight female predominance. They presented as painless nodules, mainly on the extremities or face. Local excision was the treatment of choice and up to date follow-up reveals no sign of recurrence. Histologically, eight cases were polypoid, while three cases were endophytic. The tumours were composed of elongated spindle-shaped to polygonal or round cells with prominent granular cell change, and tumour nuclei showing mild focal atypia to rare moderate atypia. Mitotic activity ranged from one to nine mitoses per 10 high-power fields (median = 2, mean = 3.8). Immunohistochemical labelling of the tumour cells demonstrated expression for NKI-C3 (n = 11), focal, weak positivity for CD68 (n = 10) and FXIIIa (n = 2). There was negative staining for S100 protein, smooth muscle actin, Melan-A, CD34, desmin and cytokeratin. CONCLUSIONS: This analysis of 11 cases contributes to the characterization of this recently described entity, which despite some atypical histological features and no obvious line of differentiation, behaves in a completely indolent fashion.

Vascular endothelial growth factor expression correlates with tumour grade and vascularity in gliomas.

AIMS: Tumour vascularity and vascular endothelial growth factor (VEGF) expression were studied in 41 primary brain tumours of astrocytic and oligodendroglial origin, in order to define the potential role of VEGF in the vascularization and growth of these tumours. METHODS AND RESULTS: Two commercial monoclonal antibodies to the VEGF protein (from R&D Systems and NeoMarkers), raised against different isoforms, were utilized. Each monoclonal antibody consistently detected the expression of VEGF in different cell types. The R&D Systems antibody only produced surface staining of endothelial cells in tumour capillaries, whereas staining with the Neomarkers antibody was largely confined to tumour cell cytoplasm. High levels of staining were seen with the R&D Systems and NeoMarkers antibodies in 13 and 14 of 15 glioblastomas, respectively, four and three of five oligodendrogliomas, four and seven of 10 anaplastic astrocytomas, one and three of six low-grade astrocytomas and none and none of five pilocytic astrocytomas. There was a close correlation between VEGF expression, tumour vascularity and grade. CONCLUSIONS: These findings support a role for VEGF in the angiogenesis of glioblastoma, anaplastic astrocytoma and oligodendroglioma. The distinct immunoreactivities of the two commercial monoclonal antibodies indicate either there is expression of different splice variants of VEGF or that the epitopes are differentially revealed during synthesis, secretion and receptor-binding of the growth factor. This highlights the importance of using more than one antibody in the evaluation of tissue VEGF expression.

An audit of pathology lymph node dissection techniques in pylorus preserving Kausch-Whipple pancreatoduodenectomy specimens.

AIMS: To determine whether or not identifying recognised anatomical groupings of lymph nodes (LNs) improves LN yield in pancreatoduodenectomy resection specimens. METHODS: All the pathology reports from pancreatoduodenectomy resection specimens between January 1997 and September 1999, for one specialist pathologist at the Royal Liverpool University Hospital, were examined retrospectively. The total number of LNs found in each specimen was determined and the method of identifying LNs established for each case. LNs were found using either (1) the UICC TNM anatomical groupings, termed "grouped"; (2) the Japanese Pancreatic Society classification, termed "numbered"; or (3) neither the "grouped" nor "numbered" classification, termed "non-grouped". RESULTS: A total of 50 reports (45 neoplastic, five chronic pancreatitis) were studied, 11 with non-grouped LNs, 14 with grouped LNs, and 25 with numbered LNs, including the five inflammatory cases. A median of 7.0 LNs was found in non-grouped cases, a significantly lower number than in the grouped cases (median, 12.0; Mann-Whitney U, p < 0.039) and numbered cases (median, 17.0; p < 0.0001). There was no significant difference in the LN yield between grouped and numbered cases (p = 0.1066). LNs were found most frequently in the inferior, posterior pancreaticoduodenal, and infrapyloric regions. CONCLUSIONS: A detailed knowledge of the anatomical distribution of LNs in pancreatoduodenectomy resection specimens significantly improves LN yield. It is suggested that illustrations of LN sites in resection specimens should be included in pathology guidelines/proformas to improve LN detection and, therefore, pathological prognostic data.