Hidradenitis suppurativa (acne inversa) is a chronic suppurative and scarring inflammatory disease with predilection in the apocrine gland-bearing areas. Histological investigations in the 1990s showed keratotic occlusion of the terminal follicle structure to be the initial cause. Our investigations describe and reproduce the morphology and try to figure out very early lesions of HS. A total of 262 operative specimens from 60 patients were investigated by routine histology and 11 operative specimens by immunohistochemistry: HS is dominated by a heterogeneous histological image. 82% of the surgical specimens showed mild or pronounced follicular hyperkeratosis, whereas an isotopic hyperplasia of follicular epithelium was evident in 77%. Pronounced perifolliculitis was seen in 68% and rupture of the follicle structure in 28%. Features which had not so far been described in detail were: epidermal psoriasiform hyperplasia (43%) and subepidermal interfollicular inflammatory infiltrate (78%). In all 11 specimens, immunohistochemical investigations showed a perifollicular and subepidermal inflammation of CD-3-, CD-4-, CD-68-, CD-79- and CD-8-cells, the latter with a striking selective epitheliotropism. To conclude, we could show follicular hyperkeratosis and lymphocytic perifollicular inflammation as early patterns in pathogenesis, whereas rupture of the follicle structure takes place later. Finally, it seems that there are two hot spots of inflammatory events (perifollicular and subepidermal) composed of a comparable inflammatory cell mixture. The CD-8 cell epitheliotropism (follicular and epidermal) described here and its influence in follicular hyperkeratosis, in hyperplasia of follicular epithelium and in epidermal psoriasiform hyperplasia will be of further interest, for instance, concerning early pharmacological intervention.

SummaryBackground Acral lentiginous melanoma (ALM) is one of the four major subtypes in cutaneous melanoma (CM). Although ALM has a poorer prognosis than other CM subtypes, the prognostic factors associated with ALM have only been verified in small-sized cohorts because of the low incidence of ALM worldwide. Objectives To investigate the clinical characteristics of ALM and to evaluate their prognostic values based on a large dataset from the Central Malignant Melanoma Registry (CMMR) of the German Dermatologic Society. Methods The Kaplan-Meier method was used to estimate the potential influence of clinical and histological parameters on ALM disease-specific survival (DSS) curves, which were compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors for DSS. Results In total, 2050 patients with ALM were identified from 58 949 patients with CM recorded by the CMMR with follow-up data. In multivariate analyses, age (P = 0Á006), ulceration (P = 0Á013), tumour thickness (P < 0Á001) and tumour spread (P < 0Á001) turned out to be significant prognostic factors for DSS in ALM whereas sex, nevus association and level of invasion were not independent factors. Conclusions ALM has the same prognostic factors as other subtypes of melanoma. Unfavourable prognosis probably derives from the delay in diagnosis in comparison with other melanoma subtypes.

OBJECTIVES: To analyze diffusion-weighted imaging (DWI) findings of meningiomas and to compare them with tumor grade, cell count, and proliferation index and to test a possibility of use of apparent diffusion coefficient (ADC) to differentiate benign from atypical/malignant tumors. METHODS: Forty-nine meningiomas were analyzed. DWI was done using a multislice single-shot echo-planar imaging sequence. A polygonal region of interest was drawn on ADC maps around the margin of the lesion. In all lesions, minimal ADC values (ADCmin) and mean ADC values (ADCmean) were estimated. Normalized ADC (NADC) was calculated in every case as a ratio ADCmean meningioma/ADCmean white matter. All meningiomas were surgically resected and analyzed histopathologically. The tumor proliferation index was estimated on Ki-67 antigen–stained specimens. Cell density was calculated. Collected data were evaluated by means of descriptive statistics. Analyses of ADC/NADC values were performed by means of two-sided t tests. RESULTS: The mean ADCmean value was higher in grade I meningiomas in comparison to grade II/III tumors (0.96 vs 0.80 × 10− 3 mm2s− 1, P = .006). Grade II/III meningiomas showed lower NADC values in comparison to grade I tumors (1.05 vs 1.26, P = .015). There was no significant difference in ADCmin values between grade I and II/III tumors (0.69 vs 0.63 × 10− 3 mm2s− 1, P = .539). The estimated cell count varied from 486 to 2091 (mean value, 1158.20 ± 333.74; median value, 1108). There were no significant differences in cell count between grade I and grade II/III tumors (1163.93 vs 1123.86 cells, P = .77). The mean level of the proliferation index was 4.78 ± 5.08%, the range was 1% to 18%, and the median value was 2%. The proliferation index was statistically significant higher in grade II/III meningiomas in comparison to grade I tumors (15.43% vs 3.00%, P = .001). Ki-67 was negatively associated with ADCmean (r = − 0.61, P < .001) and NADC (r = − 0.60, P < .001). No significant correlations between cell count and ADCmean (r = − 0.20, P = .164) or NADC (r = − 0.25, P = .079) were found.ADCmin correlated statistically significant with cell count (r = − 0.44, P = .002) but not with Ki-67 (r = − 0.22, P = .129). Furthermore, the association between ADCmin and cell count was stronger in grade II/III tumors (r = − 0.79, P = .036) versus grade I meningiomas (r = − 0.41, P = .008). An ADCmean value of less than 0.85 × 10− 3 mm2s− 1 was determined as the threshold in differentiating between grade I and grade II/III meningiomas (sensitivity 72.9%, specificity 73.1%, accuracy 73.0%). The positive and negative predictive values were 33.3% and 96.8%, respectively. The same threshold ADCmean value was used in differentiating between tumors with Ki-67 level ≥ 5% and meningiomas with low proliferation index (Ki-67 < 5%). This threshold yielded a sensitivity of 70.6%, a specificity of 81.2%, and an accuracy of 77.6%. The positive and negative predictive values were 66.6% and 83.9%, respectively. CONCLUSIONS: Grade II/III tumors had lower ADCme...

Purpose: Cancers have developed a number of strategies to escape immune responses including the differential expression of costimulatory molecules of the B7 family. B7-H3 and B7-H4 have recently been described in different tumor entities but the relevance for melanoma has not yet been studied so far.Experimental Design: Using immunohistochemistry, B7-H3 and B7-H4 expression was studied on 29 melanoma lesions. Survival curves and log-rank tests were used to test the association of protein expression with survival. Cell lines were evaluated for B7-H3 and B7-H4 expression by PCR and flow cytometry. Functional T-cell-tumor coculture assays were carried out with in vitro generated tumor transfectants.Results: B7-H3 and B7-H4 expression was detected in primary tumor lesions (29 of 29 and 28 of 29) and in metastases (28 of 29 and 26 of 29). The numbers of CD68 þ macrophages were significantly lower in patients with low B7-H4 expression, whereas CD8 þ T-cell infiltrates were independent of expression levels.Furthermore, a survival benefit for patients with B7-H4 low expressing melanoma was found, whereas B7-H3 was not associated with any clinical parameter. All 23 melanoma cell lines analyzed expressed B7-H3 and B7-H4 mRNA and protein, but B7-H4 was restricted to intracellular compartments. On silencing of B7-H3 by specific shRNA tumor-associated antigen-specific T cell responses were unaltered. Overexpression of B7-H4 on melanoma cells did not alter the cytotoxicity of different CD8 þ effector cells, but drastically inhibited cytokine production. Conclusions: Our study provides for the first time evidence of B7-H4 expression on melanoma cells as a mechanism controlling tumor immunity which is associated with patients' survival. Clin Cancer Res; 17(10); 3100-11. Ó2011 AACR.

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