Evita T. Sadimin

Detailed analysis of patients with metastasis to the prostatic anterior fat pad lymph nodes: a multi-institutional study.

PURPOSE Lymph nodes in the prostatic anterior fat pad rarely harbor metastatic disease. Therefore, the characteristics of patients with prostatic anterior fat pad lymph node metastasis are not well described in the literature. We identified the perioperative characteristics and assessed the clinical outcomes of patients with prostatic anterior fat pad lymph node metastasis. MATERIALS AND METHODS At 8 tertiary care centers a total of 4,261 patients underwent complete removal and pathological analysis of the prostatic anterior fat pad. We describe preoperative and pathological characteristics, and clinical management and outcomes in patients with metastatic disease to the prostatic anterior fat pad. RESULTS Metastatic disease to the prostatic anterior fat pad lymph nodes was detected in 40 patients (0.94%), of whom 37 (92.5%) had intermediate or high risk features preoperatively. Most patients with prostatic anterior fat pad metastases underwent concomitant pelvic lymph node dissection, and adjuvant therapy with radiation, androgen ablation and/or chemotherapy. A total of 27 patients (67.5%) with prostatic anterior fat pad metastatic disease were up-staged as a result of prostatic anterior fat pad pathological analysis, of whom 14 (51.8%) remained free of biochemical recurrence with observation and/or definitive adjuvant/salvage therapy. CONCLUSIONS Most patients with prostatic anterior fat pad metastatic disease had intermediate to high risk features preoperatively. In some patients with such lymph node metastasis removing these lymph nodes resulted in prolonged biochemical recurrence-free survival. Therefore, we recommend that the prostatic anterior fat pad be removed in all patients undergoing radical prostatectomy. However, pathological analysis of the prostatic anterior fat pad may be limited to patients with intermediate to high risk oncological features preoperatively.

Interobserver Reproducibility of Percent Gleason Pattern 4 in Prostatic Adenocarcinoma on Prostate Biopsies

In the WHO Classification of Tumours of the Urinary System and Male Genital Organs published in 2016, it was officially recommended that the percent of Gleason pattern 4 (GP4) be reported on pathology reports to better reflect the extent in Gleason score 7 tumors. In this study we assessed the reproducibility of reporting GP4 on prostate biopsies. We analyzed prospectively 422 cores containing GP4 from our consult cases over a period of 2.5 months. The percent pattern 4 was assigned to all the cases in 10% increments from 0% to 100% (with the addition of 5%) by 1 of 4 fellows in urological pathology and by the expert urological pathologist. Out of 422 cores, 32% were an exact match and 75% were within ±10% (weighted &kgr; [&kgr;W] value 0.67). Cases were further stratified on the basis of (1) scattered versus clustered GP4 in the background of Gleason pattern 3, (2) continuous versus discontinuous tumor involvement, (3) cribriform/glomeruloid pattern only versus poorly formed/fused pattern versus mixed cribriform and poorly formed/fused pattern, and (4) total tumor involvement of the core (⩽10% vs. >10% of the core). No significant differences were observed in the first 3 variables. However, in cases with ⩽10% involvement of the core, 61% were within ±10% (&kgr;W=0.50) compared with cases with >10% involvement of the core, in which 78% were within ±10% (&kgr;W=0.70). In summary, we showed that assessment of percent GP4 was relatively reproducible, with substantial agreement within ±10% in cases. However, with <10% involvement of the core, it was more difficult to assess in smaller foci, with only moderate agreement. Given that in a small focus only a few glands of a given pattern can markedly affect the percent GP4, consideration should be given to not recording percent GP4 in small foci of Gleason score 7 tumors on needle biopsy.

Round cell pattern of prostatic stromal tumor of uncertain malignant potential: a subtle newly recognized variant.

Prostatic stromal tumor of uncertain malignant potential (STUMP) is a distinct entity which includes several different patterns. Four patterns of STUMP have been described including stroma with (1) degenerative atypia, (2) hypercellular spindle cells, (3) myxoid spindle cells, and (4) phyllodes-like pattern. The current study identified a novel round cell pattern. We searched our database from 1999 to 2015 and identified 7 patients with round cell pattern out of a total number of 98 patients with STUMP. All 7 cases showed mildly increased stromal cellularity with rounded nuclei, diagnosed on core biopsies in 5 cases, transurethral resection in 1 case, and radical prostatectomy in 1 case. Some degree of glandular displacement was observed in 4 cases. In 2 of the cases, STUMP was not recognized histologically by the referring pathologists and was initially diagnosed as benign prostatic hyperplasia. As has been described with other patterns of STUMP, several cases showed associated epithelial proliferations that in some instances masked the neoplastic stromal process. The round cell pattern of STUMP is a new deceptively subtle pattern that may not be recognized as a neoplasm and may be misdiagnosed as benign prostatic hyperplasia. Although there was no direct evidence in our study that the round cell pattern of STUMP has the same behavior as other variants of STUMPs, increased recognition of this entity will hopefully lead to additional studies to further understand its malignant potential.

Computer aided analysis of prostate histopathology images Gleason grading especially for Gleason score 7

Clinically, prostate adenocarcinoma is diagnosed by recognizing certain morphology on histology. While the Gleason grading system has been shown to be the strongest prognostic factor for men with prostrate adenocarcinoma, there is a significant intra and interobserver variability between pathologists in assigning this grading system. In this study, we present a new method for prostate gland segmentation from which we then utilize to develop a computer aided Gleason grading. The novelty of our method is a region-based nuclei segmentation to get individual gland without using lumen as prior information. Because each gland region is surrounded by nuclei, individual gland can be segmented by using the structure features and Delaunay Triangulation. The precision, recal and F1 of this approach are 0.94±0.11, 0.60±0.23 and 0.70±0.19 respectively. Our method achieves a high accuracy for prostate gland segmentation with less computation time.

CNS lymphoma in a patient with Shwachman Diamond syndrome.

To the Editor: Shwachman Diamond syndrome (SDS) is a rare autosomal disorder characterized by pancreatic insufficiency and neutropenia. Patients commonly present in infancy and are at risk for hematological malignancy in life [2,3]. The association of SDS and myelodysplasia, ALL and AML are well described [1]. We present the case of an 18-year-old patient with SDS who is diagnosed with CNS B-cell lymphoma. To our knowledge, CNS lymphoma in a patient with SDS has not been described [4]. Our 18-year-old patient with SDS presented with new onset seizures. He was initially diagnosed with the syndrome at age 8 when he was admitted for a respiratory infection and was noted to be neutropenic during the admission. A bone marrow biopsy was performed which confirmed hypoplasia of myeloid tissue and maturation arrest of myeloid cells. An outside institution confirmed presence of the SDS gene. However, this test was not duplicated at our institution. From age 8 to 18 years, he was maintained on pancreatic enzymes and had no hospitalizations for infections. At 18, he had a generalized tonic-clonic seizure, which lasted about 10minutes. A CT of the head was performed which revealed a right frontal hemorrhage or hemorrhagicmass with surrounding edema. AnMRI was performed which confirmed a 3 cm right frontal and 1 cm left occipital enhancing lesions (see Fig. 1). These lesions were biopsied and confirmed to be diffuse large B-cell lymphoma. The brain biopsy obtained from the patient shows neoplastic infiltrate of atypical cells in large clusters and in perivascular pattern that are positive for CD45, CD20, PAX5, CD30 and negative for CD2, CD3, CD5, CD10. There are areas of tumor necrosis as well as individual cell necrosis. The morphology and the immunohistochemical staining pattern are consistent with large B-cell lymphoma (see Fig. 2). The patient was treated with rituximab, vincristine, prednisone, and intrathecal methotrexate/hydrocortisone/cytarabine. A followupMRI performed 6 months after initial diagnosis showed minimal improvement in size of the lesions. Time in treatment was complicated by seizures and hospitalizations for neutropenic fever.

A phase II trial of riluzole, an antagonist of metabotropic glutamate receptor 1 (GRM1) signaling, in patients with advanced melanoma

Studies demonstrate that GRM, expressed by >60% of human melanomas, may be a therapeutic target. We performed a phase II trial of 100 mg PO bid of riluzole, an inhibitor of GRM1 signaling, in patients with advanced melanoma with the primary endpoint of response rate. Thirteen patients with GRM1‐positive tumors were enrolled. No objective responses were observed, and accrual was stopped. Stable disease was noted in six (46%) patients, with one patient on study for 42 weeks. Riluzole was well tolerated, with fatigue (62%) as the most common adverse event. Downregulation of MAPK and PI3K/AKT was noted in 33% of paired tumor biopsies. Hypothesis‐generating correlative studies suggested that downregulation of angiogenic markers and increased leukocytes at the active edge of tumor correlate with clinical benefit. Pharmacokinetic analysis showed interpatient variability consistent with prior riluzole studies. Future investigations should interrogate mechanisms of biologic activity and advance the development of agents with improved bioavailability.

Accuracy of Grading Gleason Score 7 Prostatic Adenocarcinoma on Needle Biopsy: Influence of Percent Pattern 4 and Other Histological Factors

Recognition of Gleason pattern 4 in prostatic needle biopsies is crucial for both prognosis and therapy. Recently, it has been recommended to record percent pattern 4 when Gleason score 7 cancer is the highest grade in a case.

Computer aided analysis of prostate histopathology images to support a refined Gleason grading system

The Gleason grading system used to render prostate cancer diagnosis has recently been updated to allow more accurate grade stratification and higher prognostic discrimination when compared to the traditional grading system. In spite of progress made in trying to standardize the grading process, there still remains approximately a 30% grading discrepancy between the score rendered by general pathologists and those provided by experts while reviewing needle biopsies for Gleason pattern 3 and 4, which accounts for more than 70% of daily prostate tis- sue slides at most institutions. We propose a new computational imaging method for Gleason pattern 3 and 4 classification, which better matches the newly established prostate cancer grading system. The computer- aided analysis method includes two phases. First, the boundary of each glandular region is automatically segmented using a deep convolutional neural network. Second, color, shape and texture features are extracted from superpixels corresponding to the outer and inner glandular regions and are subsequently forwarded to a random forest classifier to give a gradient score between 3 and 4 for each delineated glandular region. The F1 score for glandular segmentation is 0.8460 and the classification accuracy is 0.83±0.03.

Chromosomal Abnormalities of High Grade Mucinous Tubular and Spindle Cell Carcinoma of the Kidney

Mucinous tubular and spindle cell carcinoma (MTSC) of the kidney is a distinct entity characterized by bland tightly packed elongated tubules and spindle cells with low nucleolar grade in a basophilic mucinous stroma. Several case studies have reported MTSC with high‐grade features and have brought into question whether they represented MTSC or a variant of papillary renal cell carcinoma.

Polypoid endometriosis presenting as a renal cortical tumor

A 41-year-old female patient presented with left-sided flank pain and gross hematuria temporally unrelated to her menstrual cycle. Abdominal computed tomography scan showed a large left-sided solid, enhancing kidney mass radiographically consistent with renal cell carcinoma. Following surgical resection, histopathological examination revealed polypoid endometriosis. Polypoid endometriosis is rare and mimics a neoplasm clinically, radiographically, and on gross examination. Patients with polypoid endometriosis often present with symptoms related to mass effect rather than classic endometriosis hallmark symptoms such as dyspareunia, dysmenorrhea, and cyclic abdominal pain. Treatment includes surgical resection.