Prostatic nerve subtypes independently predict biochemical recurrence in prostate cancer.

OBJECTIVE: To describe nerve subtypes involved by perineural invasion (PNI) in prostate cancer and their relationship with clinicopathological parameters and recurrence risk. METHODS: 141 prostatectomy specimens from men with localized prostate cancer and known perineural invasion were analyzed. Index tumor blocks were stained for perineural invasion and sympathetic/parasympathetic markers. For 98 patients with complete staining, nerves from up to three hotspot regions of intraprostatic perineural invasion were classified according to autonomic subtype and perineural invasion status. Findings were correlated with prospectively collected clinicopathological data. Biochemical recurrence predictors were tested in univariable and multivariable models. RESULTS: Most intra-prostatic nerves contained sympathetic and parasympathetic fibres, irrespective of perineural invasion status. A fraction was purely sympathetic (5% PNI, 2% non-PNI) or double-negative (non-adrenergic, non-nitrergic; 1% PNI, 1% non-PNI). Perineural invasion nerve count was associated with higher pathological stage. Although total perineural invasion or non-perineural invasion nerve count did not predict biochemical recurrence, two subtypes were found to be independent predictors: pure sympathetic non-perineural invasion nerves (HR 6.79, p = 0.03) and non-adrenergic, non-nitrergic PNI nerves (HR 10.56, p < 0.005). CONCLUSIONS: Pure sympathetic nerve density without tumour invasion and perineural invasion specifically involving non-adrenergic, non-nitrergic fibres are independent predictors of biochemical recurrence post prostatectomy, supporting a role for the autonomic nervous system in prostate cancer progression.

Three-Dimensional Pathology Specimen Modeling Using "Structure-From-Motion" Photogrammetry: A Powerful New Tool for Surgical Pathology.

CONTEXT.­: Three-dimensional (3D) photogrammetry is a method of image-based modeling in which data points in digital images, taken from offset viewpoints, are analyzed to generate a 3D model. This modeling technique has been widely used in the context of geomorphology and artificial imagery, but has yet to be used within the realm of anatomic pathology. OBJECTIVE.­: To describe the application of a 3D photogrammetry system capable of producing high-quality 3D digital models and its uses in routine surgical pathology practice as well as medical education. DESIGN.­: We modeled specimens received in the 2 participating laboratories. The capture and photogrammetry process was automated using user control software, a digital single-lens reflex camera, and digital turntable, to generate a 3D model with the output in a PDF file. RESULTS.­: The entity demonstrated in each specimen was well demarcated and easily identified. Adjacent normal tissue could also be easily distinguished. Colors were preserved. The concave shapes of any cystic structures or normal convex rounded structures were discernable. Surgically important regions were identifiable. CONCLUSIONS.­: Macroscopic 3D modeling of specimens can be achieved through Structure-From-Motion photogrammetry technology and can be applied quickly and easily in routine laboratory practice. There are numerous advantages to the use of 3D photogrammetry in pathology, including improved clinicopathologic correlation for the surgeon and enhanced medical education, revolutionizing the digital pathology museum with virtual reality environments and 3D-printing specimen models.

Routinely reported 'equivocal' lymphovascular invasion in prostatectomy specimens is associated with adverse outcomes.

OBJECTIVE: To evaluate the significance of routinely reported 'equivocal' lymphovascular invasion (LVI) in prostatectomy specimens of patients with clinically localized prostate cancer. MATERIALS AND METHODS: Prospectively collected data from men who underwent prostatectomy for clinically localized prostate cancer were retrospectively reviewed. Rates of adverse pathological features and biochemical recurrence (BCR) were compared between tumours positive, negative or 'equivocal' for LVI. Multivariable Cox regression analysis was performed to identify independent predictors of BCR. RESULTS: Of 1 310 consecutive cases, LVI was present definitively in 82 (6.3%) and equivocally in 43 (3.3%) cases. Similar to definitive LVI, equivocal LVI was significantly associated with other adverse pathological features, including advanced stage, higher Gleason grade and positive surgical margins. BCR occurred more frequently in patients with tumours that were equivocal (61%) or positive for LVI (71%) than in patients with negative results (14.7%). In addition, patients with both definitive and equivocal LVI had a significantly shorter BCR-free survival time compared with those with negative LVI. Multivariable Cox regression analysis indicated that the presence of either definitive or equivocal LVI were independent predictors of disease recurrence (hazard ratio [HR] 3.32, 95% confidence interval [CI] 2.3-4.8; P <0.001 vs HR 1.66, 95% CI 1.05-2.65; P = 0.032, respectively). CONCLUSION: In this single-institution study, equivocal LVI had a similar association with adverse pathological features and rate of BCR to that of definitive LVI. If our observations are validated in an independent cohort, consideration should be given to the inclusion of equivocal LVI as part of routine pathological reporting.

High-resolution Map of Somatic Periprostatic Nerves.

OBJECTIVE: To generate a high-resolution map of periprostatic somatic nerves. Periprostatic nerves are at risk of injury during radical prostatectomy; this study aimed to establish the location of somatic nerves with respect to the prostate and the neurovascular bundle. MATERIALS AND METHODS: Hemiprostates from patients in whom a wide local excision was performed were evaluated. Representative sections from the base, midzone, and apex of the prostate were stained with Masson's trichrome and antineuronal nitric oxide synthase antibodies, to identify myelinated and parasympathetic nerves, respectively. Somatic nerves were identified as neuronal nitric oxide synthase negative myelinated nerves. Stained slides were scanned (40× objective) for digital analysis. Location of nerves was described with reference to 6 equal sectors per hemiprostate. RESULTS: Somatic nerves account for almost 5% of all nerve fibers in the periprostatic tissue. This study found a mean somatic nerve count of 5.83, 5.25, and 3.67 at the level of the prostate base, midzone, and apex, respectively. These nerves are most frequently located either anteriorly or in the region of the neurovascular bundle (posterolateral). CONCLUSION: Somatic nerves in the periprostatic region are at risk of injury during radical prostatectomy. Further research is required to clarify their functional relevance.

Subungual fibro-osseous pseudotumour of the toe.

Subungual fibro-osseous pseudotumour of the toe is a rare osseous soft tissue tumour of which only six cases have been described in the literature. We present a case in a teenage boy that posed an instructive diagnostic challenge and discuss the distinguishing features of the various differential diagnoses. The subungual location is very rare. For such tumours, radiology is as vital as histopathology in making a diagnosis and excluding neoplasia. Accurate diagnosis requires careful clinico-pathological and radiological correlation. These sorts of lesions may present to the dermatologist, not always the foot surgeon.

Does perineural invasion in a radical prostatectomy specimen predict biochemical recurrence in men with prostate cancer?

INTRODUCTION: The ability of perineural invasion (PNI) in radical prostatectomy (RP) specimens to predict biochemical recurrence (BCR) is unclear. This study investigates this controversial question in a large cohort. METHODS: A retrospective analysis was undertaken of prospectively collected data from 1497 men who underwent RP (no neoadjuvant therapy) for clinically localized prostate cancer. The association of PNI at RP with other clinicopathological parameters was evaluated. The correlation of clinicopathological factors and BCR (defined as prostate-specific antigen [PSA] >0.2 ng/mL) was investigated with univariable and multivariable Cox regression analysis in 1159 men. RESULTS: PNI-positive patients were significantly more likely to have a higher RP Gleason score, pT3 disease, positive surgical margins, and greater cancer volume (p < 0.0005). The presence of PNI significantly correlated with BCR on univariable (hazard ratio 2.30, 95% confidence interval 1.50-3.55, p < 0.0005), but not multivariable analysis (p = 0.602). On multivariable Cox regression analysis the only independent prognostic factors were preoperative PSA, RP Gleason score, pT-stage, and positive surgical margin status. These findings are limited by a relatively short follow-up time and retrospective study design. CONCLUSIONS: PNI at RP is not an independent predictor of BCR. Therefore, routine reporting of PNI is not indicated. Future research should be targeted at the biology of PNI to increase the understanding of its role in prostate cancer progression.

Pulmonary metastases: a rare manifestation of the most common cancer.

Basal cell carcinoma (BCC) is the most common human malignancy but rarely metastasises. We report on two patients with symptomatic lung metastases and a past history of recurrent BCC excisions. In our first patient, a heavy smoker with multiple lung lesions, histology of a resected nodule was first reported as non-small cell lung cancer but a repeat nodule biopsy a year later was recognised as a pulmonary metastasis from primary cutaneous BCC. Our second patient, a young never-smoker with two previous BCC, was confirmed as having a pulmonary metastasis from BCC on the lung resection specimen. Pulmonary metastasis from an unidentified primary site is a common clinical situation. These patients emphasise the importance of considering the most common cancer as a potential primary.