Conjunctival MALT lymphoma: utility of FDG PET/CT for diagnosis, staging, and evaluation of treatment response.

A 67-year-old woman was referred for staging of a mucosa-associated lymphoid tumor lymphoma involving the left conjunctiva. CT scan had shown paravertebral and pelvic masses, and a breast nodule. FDG PET/CT demonstrated moderately increased uptake in the left ocular conjunctiva and confirmed the paravertebral and pelvic masses and the breast nodule. Moreover, abnormal FDG uptake was shown in 2 breast nodules, the flank, the gluteus maximus, and the gastric cardia. The patient received 6 cycles of rituximab-bendamustine chemotherapy with a complete clinical and metabolic response at the 6-month follow-up PET/CT and remained relapse-free without visual acuity problem after a 36-month follow-up.

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 2: T2 substaging and prostate cancer volume.

The 2009 International Society of Urological Pathology consensus conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the substaging of pT2 prostate cancers according to the TNM 2002/2010 system, reporting of tumor size/volume and zonal location of prostate cancers were coordinated by working group 2. A survey circulated before the consensus conference demonstrated that 74% of the 157 participants considered pT2 substaging of prostate cancer to be of clinical and/or academic relevance. The survey also revealed a considerable variation in the frequency of reporting of pT2b substage prostate cancer, which was likely a consequence of the variable methodologies used to distinguish pT2a from pT2b tumors. Overview of the literature indicates that current pT2 substaging criteria lack clinical relevance and the majority (65.5%) of conference attendees wished to discontinue pT2 substaging. Therefore, the consensus was that reporting of pT2 substages should, at present, be optional. Several studies have shown that prostate cancer volume is significantly correlated with other clinicopathological features, including Gleason score and extraprostatic extension of tumor; however, most studies fail to demonstrate this to have prognostic significance on multivariate analysis. Consensus was reached with regard to the reporting of some quantitative measure of the volume of tumor in a prostatectomy specimen, without prescribing a specific methodology. Incorporation of the zonal and/or anterior location of the dominant/index tumor in the pathology report was accepted by most participants, but a formal definition of the identifying features of the dominant/index tumor remained undecided.

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 1: specimen handling.

The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the handling and processing of radical prostatectomy specimens were coordinated by working group 1. Most uropathologists followed similar procedures for fixation of radical prostatectomy specimens, with 51% of respondents transporting tissue in formalin. There was also consensus that the prostate weight without the seminal vesicles should be recorded. There was consensus that the surface of the prostate should be painted. It was agreed that both the prostate apex and base should be examined by the cone method with sagittal sectioning of the tissue sample. There was consensus that the gland should be fully fixed before sectioning. Both partial and complete embedding of prostates was considered to be acceptable as long as the method of partial embedding is stated. No consensus was determined regarding the necessity of weighing and measuring the length of the seminal vesicles, the preparation of whole mounts rather than standardized blocks and the methodology for sampling of fresh tissue for research purposes, and it was agreed that these should be left to the discretion of the working pathologist.

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 5: surgical margins.

The 2009 International Society of Urological Pathology Consensus Conference in Boston, made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to surgical margin assessment were coordinated by working group 5. Pathologists agreed that tumor extending close to the 'capsular' margin, yet not to it, should be reported as a negative margin, and that locations of positive margins should be indicated as either posterior, posterolateral, lateral, anterior at the prostatic apex, mid-prostate or base. Other items of consensus included specifying the extent of any positive margin as millimeters of involvement; tumor in skeletal muscle at the apical perpendicular margin section, in the absence of accompanying benign glands, to be considered organ confined; and that proximal and distal margins be uniformly referred to as bladder neck and prostatic apex, respectively. Grading of tumor at positive margins was to be left to the discretion of the reporting pathologists. There was no consensus as to how the surgical margin should be regarded when tumor is present at the inked edge of the tissue, in the absence of transected benign glands at the apical margin. Pathologists also did not achieve agreement on the reporting approach to benign prostatic glands at an inked surgical margin in which no carcinoma is present.

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 3: extraprostatic extension, lymphovascular invasion and locally advanced disease.

The International Society of Urological Pathology Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to extraprostatic extension (pT3a disease), bladder neck invasion, lymphovascular invasion and the definition of pT4 were coordinated by working group 3. It was agreed that prostate cancer can be categorized as pT3a in the absence of adipose tissue involvement when cancer bulges beyond the contour of the gland or beyond the condensed smooth muscle of the prostate at posterior and posterolateral sites. Extraprostatic extension can also be identified anteriorly. It was agreed that the location of extraprostatic extension should be reported. Although there was consensus that the amount of extraprostatic extension should be quantitated, there was no agreement as to which method of quantitation should be employed. There was overwhelming consensus that microscopic urinary bladder neck invasion by carcinoma should be reported as stage pT3a and that lymphovascular invasion by carcinoma should be reported. It is recommended that these elements are considered in the development of practice guidelines and in the daily practice of urological surgical pathology.

Accuracy of sentinel lymph node dissection for melanoma staging in the presence of a collision tumour with a lymphoproliferative disease.

Sentinel lymph node dissection (SLND) identifies melanoma patients with metastatic disease who would benefit from radical lymph node dissection (RLND). Rarely, patients with melanoma have an underlying lymphoproliferative disease, and melanoma metastases might develop as collision tumours in the sentinel lymph node (SLN). The aim of this study was to measure the incidence and examine the effect of collision tumours on the accuracy of SLND and on the validity of staging in this setting. Between 1998 and 2012, 750 consecutive SLNDs were performed in melanoma patients using the triple technique (lymphoscintigraphy, gamma probe and blue dye). The validity of SLND in collision tumours was analysed. False negativity was reflected by the disease-free survival. The literature was reviewed on collision tumours in melanoma. Collision tumours of melanoma and chronic lymphocytic leukaemia (CLL) were found in two SLN and in one RLND (0.4%). Subsequent RLNDs of SLND-positive cases were negative for melanoma. The patient with negative SLND developed relapse after 28 months with an inguinal lymph node metastasis of melanoma; RLND showed collision tumours. The literature review identified 12 cases of collision tumours. CLL was associated with increased melanoma incidence and reduced overall survival. This is, to our knowledge, the first assessment of the clinical value of SLND when collision tumours of melanoma and CLL are found. In this small series of three patients with both malignancies present in the same lymph node basin, lymphocytic infiltration of the CLL did not alter radioisotope uptake into the SLN. No false-negative result was observed. Our data suggest the validity of SLND in collision tumours, but given the rarity of the problem, further studies are necessary to confirm this reliability.

Occult lung infarction may induce false interpretation of 18F-FDG PET in primary staging of pulmonary malignancies.

PURPOSE: The aim of the present report is to describe abnormal (18)F-fluorodeoxyglucose (FDG) accumulation patterns in the pleura and lung parenchyma in a group of lung cancer patients in whom lung infarction was present at the time of positron emission tomography (PET). METHODS: Between November 2002 and December 2003, a total of 145 patients (102 males, 43 females; age range 38-85 years) were subjected to whole-body FDG PET for initial staging (n=117) or restaging (n=11) of lung cancer or for evaluation of solitary pulmonary nodules (n=17). Of these patients, 24 displayed abnormal FDG accumulation in the lung parenchyma that was not consistent with the primary lesion under investigation (ipsilateral n=12, contralateral n=9 or bilateral n=3). Without correlative imaging, this additional FDG uptake would have been considered indeterminate in differential diagnosis. RESULTS: Of the 24 patients who were identified as having such lesions, six harboured secondary tumour nodules diagnosed as metastases, while in three the diagnosis of a synchronous second primary lung tumour was established. Additionally, nine patients were identified as having post-stenotic pneumonia and/or atelectasis (n=6) or granulomatous lung disease (n=3). In the remaining six (4% of all patients), a diagnosis of recent pulmonary embolism that topographically matched the additional FDG accumulation (SUV(max) range 1.4-8.6, mean 3.9) was made. Four of these six patients were known to have pulmonary embolism, and hence false positive interpretation was avoided by correlating the PET findings with those of the pre-existing diagnostic work-up. The remaining two patients were harbouring small occult infarctions that mimicked satellite nodules in the lung periphery. Based on histopathological results, the abnormal FDG accumulation in these two patients was attributed to the inflammatory reaction and tissue repair associated with the pathological cascade of pulmonary embolism. CONCLUSION: In patients with pulmonary malignancies, synchronous lung infarction may induce pathological FDG accumulation that can mimic active tumour manifestations. Identifying this potential pitfall may allow avoidance of false positive FDG PET interpretation.

Utilité clinique des ultrasons osseux quantitatifs dans le dépistage de l'ostéoporose [Clinical utility of quantitative bone ultrasonography in the staging of osteoporosis]

Osteoporosis is well recognized as a public health problem in industrialized countries. Because of the efficiency of new treatments to decrease fracture risk, it is of a major interest to detect the patients who should benefit from such treatments. A diagnosis of osteoporosis is necessary before to start a specific treatment. This diagnosis is based on the measurement of the skeleton (hip and spine) with dual X-ray absorptiometry, using diagnostic criteria established by the World Health Organisation (WHO). In Switzerland, indications for bone densitometry are limited to precise situations. This technique cannot be applied for screening. For this purpose, peripheral measurements and particularly quantitative ultrasounds of bone seem to be promising. Indeed, several prospective studies clearly showed their predictive power for hip fracture risk in women aged more than 65 years. In order to facilitate the clinical use of bone ultrasounds, thresholds of risk of fracture and osteoporosis of the hip will be shortly published. This will integrate bone ultrasound in a global concept including bone densitometry and its indications, but also other risk factors for osteoporosis recognized by the Swiss association against osteoporosis (ASCO).

Nodal staging in colorectal cancer: should distant lymph nodes be recovered in surgical specimens?

To assess the value of sampling lymph nodes located far sidelong colorectal cancer specimens, we analyzed retrospectively surgical specimens from 345 colorectal cancer patients. The mesocolic and perirectal fat was divided into 2 fractions: close to (<5 cm) and distant from (>5 cm) the tumor. Tumors were located in the cecum (n = 61), ascending colon (n = 29), transverse colon (n = 31), descending colon (n = 27), sigmoid colon (n = 108), and rectum (n = 89). The median number of lymph nodes sampled was 17 in both fractions (range, 4-66), 12 (range, 0-46) in the close fraction, and 3 (range, 0-33) in the distant fraction. There were 169 pN0, 104 pN1, and 72 pN2 cases. The pN staging was accurate in all cases except 10 based on the close fraction alone; of these, 6 were upstaged from pN0 to pN1 and 4 from pN1 to pN2 when the distant fraction was considered. Among pN1-upstaged cases, 5 were rectal (3/5 with neoadjuvant radiotherapy) and 1 colonic. In the colon, we found that lymph node location is more important than lymph node number because metastatic lymph nodes were present mostly in the peritumoral area. This suggests that lymph nodes should be initially recovered from the pericolic fat close to the tumor. If there are less than 4 positive lymph nodes and less than 12 lymph nodes examined in total, additional lymph nodes should be retrieved from the distal fraction for potential upstaging. In the rectum, systematic sampling of close and distant lymph nodes is mandatory because in rare cases, metastases are detected only in distant lymph nodes, particularly in patients who have undergone neoadjuvant radiotherapy.

The wound watch: an objective staging system for wounds in the diabetic (db/db) mouse model.

As in cancer biology, in wound healing there is a need for objective staging systems to decide for the best treatment and predictors of outcome. We developed in the diabetic (db/db) wound healing model, a staging system, the "wound watch," based on the quantification of angiogenesis and cell proliferation in open wounds. In chronic wounds, there is often a lack of cellular proliferation and angiogenesis that leads to impaired healing. The wound watch addresses this by quantifying the proliferative phase of wound healing in two dimensions (cellular division and angiogenesis). The results are plotted in a two-dimensional graph to monitor the course of healing and compare the response to different treatments.

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 4: seminal vesicles and lymph nodes.

The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the infiltration of tumor into the seminal vesicles and regional lymph nodes were coordinated by working group 4. There was a consensus that complete blocking of the seminal vesicles was not necessary, although sampling of the junction of the seminal vesicles and prostate was mandatory. There was consensus that sampling of the vas deferens margins was not obligatory. There was also consensus that muscular wall invasion of the extraprostatic seminal vesicle only should be regarded as seminal vesicle invasion. Categorization into types of seminal vesicle spread was agreed by consensus to be not necessary. For examination of lymph nodes, there was consensus that special techniques such as frozen sectioning were of use only in high-risk cases. There was no consensus on the optimal sampling method for pelvic lymph node dissection specimens, although there was consensus that all lymph nodes should be completely blocked as a minimum. There was also a consensus that a count of the number of lymph nodes harvested should be attempted. In view of recent evidence, there was consensus that the diameter of the largest lymph node metastasis should be measured. These consensus decisions will hopefully clarify the difficult areas of pathological assessment in radical prostatectomy evaluation and improve the concordance of research series to allow more accurate assessment of patient prognosis.

Molecular investigation of lymph nodes in patients with colon cancer: a new road to better staging

Objective: Small nodal tumor infiltrates are identified by applying multilevel sectioning and immunohistochemistry (IHC) in addition to H&E (hematoxylin and eosin) stains of resected lymph nodes. However, the use of multilevel sectioning and IHC is very time-consuming and costly. The current standard analysis of lymph nodes in colon cancer patients is based on one slide per lymph node stained by H&E. A new molecular diagnostic system called ''One tep Nucleic Acid Amplification'' (OSNA) was designed for a more accurate detection of lymph node metastases. The objective of the present investigation was to compare the performance ofOSNAto current standard histology (H&E). We hypothesize that OSNA provides a better staging than the routine use of one slide H&E per lymph node.Methods: From 22 colon cancer patients 307 frozen lymph nodes were used to compare OSNA with H&E. The lymph nodes were cut into halves. One half of the lymph node was analyzed by OSNA. The semi-automated OSNA uses amplification of reverse-transcribed cytokeratin19 (CK19) mRNA directly from the homogenate. The remaining tissue was dedicated to histology, with 5 levels of H&E and IHC staining (CK19).Results: On routine evaluation of oneH&Eslide 7 patients were nodal positive (macro-metastases). All these patients were recognized by OSNA analysis as being positive (sensitivity 100%). Two of the remaining 15 patients had lymph node micro-metastases and 9 isolated tumor cells. For the patients with micrometastases both H&E and OSNA were positive in 1 of the 2 patients. For patients with isolated tumor cells, H&E was positive in 1/9 cases whereas OSNA was positive in 3/9 patients (IHC as a reference). There was only one case to be described as IHC negative/OSNA positive. On the basis of single lymph nodes the sensitivity of OSNA and the 5 levels of H&E and IHC was 94・5%.Conclusion: OSNA is a novel molecular tool for the detection of lymph node metastases in colon cancer patients which provides better staging compared to the current standard evaluation of one slide H&E stain. Since the use of OSNA allows the analysis of the whole lymph node, sampling bias and undetected tumor deposits due to uninvestigated material will be overcome. OSNA improves staging in colon cancer patients and may replace the current standard of H&E staining in the future.