Scrotal necrosis and no Fournier's in sight: a rare case of juvenile gangrenous vasculitis.

Juvenile gangrenous vasculitis of the scrotum is a rare entity, of which to our knowledge we describe the first documented case in the UK. It follows a typical disease course, demonstrated by an 18-year-old male who presented with three necrotic scrotal lesions; proceeded by 3 days of fever, pharyngitis and lethargy. Previous cases have been managed successfully with systemic steroids. On this occasion, surgical debridement was made of the necrotic areas under antibiotic cover and complete resolution was achieved with excellent wound healing and no evidence of recurrence. This case report discusses the importance of disease recognition and the merits of surgical management. We also add to the debate as to whether this disease is a variation of pyoderma gangrenosum or a distinct entity itself within the pantheon of scrotal gangrene.

The Prognostic Value of PIK3CA Copy Number Gain in Penile Cancer.

OBJECTIVE: To determine whether phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha (PIK3CA) copy number gain in penile cancer has prognostic value and association with histopathological parameters, human papillomavirus (HPV), and clinical outcome. METHODS: PIK3CA copy number status was assessed with fluorescence in situ hybridization in tissue microarrays generated from archival paraffin embedded blocks of 199 patients with primary penile squamous cell carcinoma (PSCC). HPV DNA was detected with INNO-LiPA assay. Follow-up data were available for 174 patients. PIK3CA copy number status was correlated with histopathological parameters, high-risk HPV, cancer-specific survival and time to recurrence. RESULTS: PIK3CA copy number gain was found in 84/199 (42%) of penile cancer cases. PIK3CA copy number gain was associated with tumor subtype, grade, and stage (P = .0028, P < .0001, and P = .0397, respectively), but not with lymph node status (P = .2902). PIK3CA copy number gain showed a tendency to associate with cancer-specific survival (HR = 1.76, 95% CI; 0.94-3.3; P = .0753). In multivariate analysis, PIK3CA copy number gain was found to have no prognostic value for cancer-specific survival (P = .677). Only lymph node metastasis, high tumor grade and stage were found to be independent prognostic factors for cancer-specific survival. CONCLUSION: PIK3CA copy number gain could be used as a marker of high-risk disease as it correlates with more aggressive PSCC histological subtypes and higher tumor grade and stage. However, it shows no significant association with lymph node metastasis or prognostic value for cancer-specific survival in PSCC.

PIK3CA copy number aberration and activation of the PI3K-AKT-mTOR pathway in varied disease states of penile cancer.

BACKGROUND: Therapeutic targeting of the PI3K-AKT-mTOR pathway may benefit patients with advanced penile squamous cell carcinoma (PSCC). OBJECTIVES: To determine the prevalence of PIK3CA copy number gain and correlate this with the activity status of PI3K-AKT-mTOR pathway in pre-malignant penile intraepithelial neoplasia (PeIN) and invasive PSCC. MATERIALS AND METHODS: Archival tissue blocks were obtained from 58 PeIN and 244 primary PSCC patients treated at St George's Hospital. PIK3CA copy number status (CNS) was assessed by fluorescence in-situ hybridisation. High-risk HPV DNA was detected with INNO-LiPA assay. p16INK4A, p-AKT and p-mTOR protein expression were assessed using immunohistochemistry (IHC). RESULTS: Increased prevalence of PIK3CA copy number gain was seen in PSCC in comparison to PeIN (84/199 (42%) vs. 10/58 (17%); p = 0.0009). Analysis of the p-AKT and p-mTOR revealed a tendency to a more common expression of cytoplasmic p-AKT (p = 0.1318), nuclear p-AKT (p<0.0001) and cytoplasmic mTOR (p = 0.0006) in PeIN than PSCC. A significant association between p-AKT cytoplasmic immunoexpression and PIK3CA CNS (p = 0.0404) was found in PeIN. CONCLUSION: Overall, PIK3CA copy number gain correlated with activation of the PI3K-AKT-mTOR pathway in PeIN and activation of this pathway is primarily involved in early penile carcinogenesis. Based on these results therapeutic targeting of this pathway in advanced PSCC is unlikely to produce significant clinical benefit. Future studies will need to focus on alternative therapeutic targets.

Analysis of the PI3K-AKT-mTOR pathway in penile cancer: evaluation of a therapeutically targetable pathway.

OBJECTIVES: To determine whether phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha (PIK3CA) copy number gain is common and could prove a useful marker for the activation status of the PI3K-AKT-mTOR pathway in penile squamous cell carcinoma (PSCC). METHODS: Fresh frozen tissue and archival blocks were collected from 24 PSCC patients with 15 matched normal penile epithelium (NPE) tissue from St George's Hospital. PIK3CA mutational and copy number status (CNS) was assessed via Sanger sequencing and fluorescence in-situ hybridisation, respectively. PIK3CA RNA expression was quantified using TaqMan gene expression assay. HPV DNA was detected with INNO-LiPA assay. p-AKT and p-mTOR protein expression were assessed using western blot and immunohistochemistry. RESULTS: PIK3CA copy number gain was found in 11/23 (48%) patients, with mutations present in only 2/24 (8%) patients. In comparison to NPE, PSCC showed significantly lower PIK3CA RNA expression (p=0.0007), p-AKT (Ser473) nuclear immunoexpression (p=0.026) and protein expression of p-AKT (Thr308) (p=0.0247) and p-mTOR (Ser2448) (p=0.0041). No association was found between PIK3CA CNS and p-AKT and p-mTOR protein expression. CONCLUSION: Based on our results the PI3K-AKT-mTOR pathway is not a key driver in PSCC carcinogenesis and the therapeutic targeting of this pathway is unlikely to produce significant clinical benefit.

A Rare and Interesting Case of a Massive Secondary Spinal Chondrosarcoma and Review of the Literature.

Chondrosarcoma, the second most common primary malignancy of the bone, is malignant cartilage forming tumour that very rarely involves the axial skeleton. It may arise as a primary bone tumour or as a secondary lesion from a preexisting benign cartilaginous neoplasm such as osteochondroma or enchondroma. A rare case of a massive secondary lumbar spine chondrosarcoma is presented. Management consisted of an initial posterior spinal stabilization and fusion and then a curative radical en bloc tumour resection. A review of the literature is also presented.

MOJE ceramic metatarsophalangeal arthroplasty: disappointing clinical results at two to eight years.

BACKGROUND: Among the surgical treatment options for osteoarthritis of the first metatarsophalangeal joint (MTPJ) are a number of different designs of total arthroplasty, including the MOJE, a ceramic press fit arthroplasty. We present a 2- to 8-year followup of 31 procedures. METHODS: Thirty-two MOJE arthroplasties were undertaken for painful hallux rigidus in 30 patients (nine male, 21 female) over 6 years (mean age 61.9; range, 37 to 76). At followup patients' symptoms, levels of function and radiographs were scored using SF-36, modified Kitaoka and AOFAS systems. Followup rate was 97%, with mean followup time 58 months (range, 28 to 97). RESULTS: Mean scores were: Kitaoka 53.8 (15 to 75), AOFAS 61.3/100 (range, 18 to 100), SF-36 physical combined 48.6 (27.6 to 58.7) SF-36 mental score 52.2 (19.5 to 62.2). Sixteen showed radiological evidence of component loosening (either lucency, subsidence or both) and one radiograph revealed component fracture. Eight implants have been revised. In patients who had not undergone subsequent fusion, 15 had less than 36 degrees of movement, nine had 36 to 45 degrees, four were in the 46 to 60 range, and only one had more than 60 degrees. There were no infections. CONCLUSION: Although previous studies have suggested favorable initial outcomes with the MOJE prosthesis, all have focused only on the early results. In our series, the reoperation rate of 26% at up to 8 years is worryingly high, especially given that 16 (52%) showed loosening. Although there appears to be a cohort of patients who have satisfactory outcomes with the MOJE, we would suggest the continued use of this implant.