PTEN, ERG, SPINK1, and TFF3 Status and Relationship in a Prostate Cancer Cohort from Jordanian Arab Population.

Background and Objectives: Prognostic biomarkers in prostate cancer (PCa) include PTEN, ERG, SPINK1, and TFF3. Their relationships and patterns of expression in PCa in developing countries, including Jordan, have not yet been investigated. Materials and Methods: A tissue microarray (TMA) of PCa patients was taken from paraffin-embedded tissue blocks for 130 patients. PTEN, ERG, SPINK1, and TFF3 expression profiles were examined using immunohistochemistry (IHC) and correlated with each other and other clinicopathological factors. Results: PTEN loss of any degree was observed in 42.9% of PCa cases. ERG and TFF3 were expressed in 59.3% and 46.5% of PCa cases, respectively. SPINK1 expression was observed in 6 out of 104 PCa cases (5.4%). Among all PCa cases (n = 104), 3.8% (n = 4) showed SPINK1+/ERG+ phenotype, 1.9% (n = 2) showed SPINK1+/ERG- phenotype, 56.7% (n = 59) showed SPINK1-/ERG+ phenotype, and 37.5% showed SPINK1-/ERG- phenotype (n = 39). Among ERG positive cases (n = 63), 6.3% were SPINK1 positive. Among SPINK1 positive cases (n = 6), 66.7% were ERG positive. SPINK1 expression was predominantly observed in a subgroup of cancers that expressed TFF3 (6/6). Additionally, a statistically significant loss of PTEN expression was observed from Gleason Score 6 (GS6) (Grade Group 1 (GG1)) to GS9-10 (GG5); (p-value 0.019). Conclusions: This is the first study to look at the status of the PTEN, ERG, SPINK1, and TFF3 genes in a Jordanian Arab population. Loss of PTEN has been linked to more aggressive prostate cancer with high GSs/GGs. SPINK1 expression was predominantly observed in a subgroup of cancers that expressed TFF3. Our results call for screening these biomarkers for grading and molecular subtyping of the disease.

Breast fat necrosis secondary to warfarin-induced calciphylaxis, a rare mimicker of breast cancer: A case report and a review of literature.

Breast fat necrosis (BFN) is usually a benign inflammatory response to breast trauma. However, an extremely rare cause of fat necrosis is calciphylaxis, a calcification of small- and medium-sized arteries causing thrombosis and ischemia. It is classified into (A) uremic (B) nonuremic-induced calciphylaxis. Calciphylaxis has been reported to be encountered in different parts of the body. However, to the best of our knowledge there is only one case in the English literature of BFN 2ry to warfarin-induced calciphylaxis. We report a 65-year-old female, known case of atrial fibrillation on warfarin, presented with a left breast mass of 4-month duration. The mass was painful and progressively enlarging. Examination of the left breast showed 7 × 4 cm mass, spanning from 10-2 o'clock, free from surrounding structures, with preserved overlying skin. However, the mass was not visualized on mammogram. Ultrasound showed a left breast lobulated hypoechoic mass containing a hyperechoic component. Biopsy showed fat necrosis. After 1 month, she presented with ulceration of the overlying skin. After wide local excision, histopathology demonstrated a calciphylaxis-induced fat necrosis. Considering the patient's background, the diagnosis was BFN secondary to warfarin-induced calciphylaxis. Hence, the warfarin was shifted to Rivaroxaban, 6 months follow-up showed no evidence of recurrence. In conclusion, the rarity of nonuremic calciphylaxis is reflected on the delay of diagnosis in some of the reported cases and the lack of grading system used to guide the management of such difficult wounds. However, keeping a high index of suspicion is important whenever such wounds are encountered with presence of risk factors other than end-stage kidney disease.

Myxoma of the renal pelvis masquerading pelviureteric stenosis: conservative limited resection with renal preservation: case presentation and literature review.

BACKGROUND: Myxoma is a relatively rare mesenchymal tumor seen mainly in the heart and skin. Renal myxomas in particular are exceptionally rare where only 17 cases were previously reported in the English Language literature. Only 2 of the 17 reported cases were located in the renal sinus/pelvis. CASE PRESENTATION: This is a case of an 18-year-old male patient who complained of right, colicky flank pain associated with abdominal pain and discomfort. Imaging findings revealed right kidney hydronephrosis with a provisional diagnosis of pelviureteric junction (PUJ) stenosis. On computed tomography, there was a very faint thin walled mass abutting the calyces, camouflaged within the dilated renal pelvis. During surgery, a polypoid mass was found at the pelviureteric junction, causing the obstruction. Histological examination showed a hypocellular, paucivascular myxoid neoplasm, with few spindle cells displaying serpentine nuclei and inconspicuous nucleoli. The tumor cells expressed immunoreactivity for vimentin, but not for S100, CD34, actin, or desmin. This will qualify as the third case of renal pelvis myxoma. CONCLUSION: Myxomas in the renal pelvis/sinus are extremely rare and can present with hydronephrosis and subtle radiological findings mimicking a PUJ stenosis. Being aware of this entity can save the patient unnecessary nephrectomy with possible preservation of the kidney.

Interobserver Variability in the Diagnosis of High-Grade Prostatic Intraepithelial Neoplasia in a Tertiary Hospital in Northern Jordan.

Prostate intraepithelial neoplasia is described as a precursor lesion to prostatic adenocarcinoma. High-grade prostate intraepithelial neoplasia (HGPIN) is classified as both grade 2 and 3 prostate intraepithelial neoplasia due to inconsistency between pathologists' findings. In our study, we assessed the interobserver variability in the diagnosis of HGPIN among genitourinary and nongenitourinary pathologists. All cases with prostate adenocarcinoma diagnosis on needle core biopsy, radical prostatectomy, and transurethral resection of prostate (TURP) between the years 2005 and 2014 were included. In total, 191 prostate cancer cases were included: 109 needle core biopsies, 45 radical prostatectomies, and 37 TURP. All were independently reviewed by 2 urologic pathologists for the presence of HGPIN. High-grade prostate intraepithelial neoplasia was diagnosed in 65 cases (34%), among which the lesion was recognized by the reporting pathologists in 36 (55%) of the cases and was missed in 29 (45%) of the cases with a κ coefficient of 0.53. There was a moderate interobserver agreement in the diagnosis of HGPIN. Consultation with genitourinary pathologist can improve HGPIN diagnosis.

The utility of PAX8 and SATB2 immunohistochemical stains in distinguishing ovarian mucinous neoplasms from colonic and appendiceal mucinous neoplasm.

OBJECTIVES: It is challenging to distinguish between primary ovarian mucinous tumors and metastatic mucinous neoplasms from the lower gastrointestinal tract, including appendiceal tumors. A combination of PAX8 and SATB2 immunohistochemical stains can be used as a diagnostic tool to distinguish between these cases. RESULTS: Immunostaining for SATB2, PAX8, CK7, CK20 and CDX2 was performed on 50 ovarian mucinous neoplasms (OMN) (39 cystadenomas, 4 borderline and 7 adenocarcinomas), 63 mucinous colorectal carcinoma (CRC), and 9 appendiceal mucinous neoplasms (AMN) [8 low grade appendiceal mucinous neoplasms (LAMN) and 1 adenocarcinoma]. PAX8 was positive in 32% of OMN and negative in all CRC and AMN cases. SATB2 was expressed in 2.0% of OMN, 77.8% of AMN, and 49.2% of CRC cases. CK7 was positive in 78.0% of OMN, 33.3% of AMN, and 9.5% of CRC cases. CK20 was expressed in 24.0% of OMN, 88.9% of OMN, and 87.3% of CRC cases. CDX2 was positive in 14.0% of OMN, 100% of AMN, and 90.5% of CRC cases. PAX8 can differentiate between OMN and AMN with high specificity but low sensitivity. CDX2 is the most sensitive marker for CRC and AMN, whereas SATB2 has better specificity.

Chondroma of the Falx Cerebri with Central Cystic Degeneration and Hemorrhage: A Case Report.

BACKGROUND Intracranial chondroma is a rare benign tumor that more commonly arises from the skull base. Chondroma arising from the falx cerebri is very rare, with only 19 cases previously reported in the literature. The imaging characteristics of intracranial chondroma and meningioma can be similar. Surgical excision and histology are required for the diagnosis. This report is of a case of intracranial chondroma that includes the imaging findings. The methods of diagnosis, management, and prognosis are discussed. CASE REPORT A 44-year-old man presented with episodes of severe headache. Magnetic resonance imaging (MRI) showed a well-defined, extra-axial, parafalcine lesion in the right frontal region. An interhemispheric craniotomy was performed. A right frontal solid and calcified tumor attached to the falx cerebri was identified and removed. Histology confirmed the diagnosis of a benign chondroma containing areas of hemorrhage and cystic degeneration. CONCLUSIONS Chondroma arising in the falx cerebri is a rare intracranial tumor that may mimic meningiomas on imaging. Awareness of the varied imaging characteristics of these benign tumors is essential for planning the most appropriate treatment.

ERG expression in prostate cancer biopsies with and without high-grade prostatic intraepithelial neoplasia: a study in Jordanian Arab patients.

Background: High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precancerous lesion for prostatic adenocarcinoma (PCa). Recent molecular studies have shown that HGPIN can harbor TMPRSS2-ERG fusion, a genetic marker also associated with PCa, which may provide an additional risk stratification tool for HGPIN, especially when present as an isolated lesion. Our aim was to assess the frequency of HGPIN and ERG expression in a cohort of prostatic needle core biopsies from Jordanian-Arab patients with PCa. Materials and methods: We studied 109 needle core biopsies from patients with PCa. Clinical data, including age and preoperative prostate specific antigen (PSA) level, were obtained from patients' medical records. Results: HGPIN was present in 31 (28.4 %) of the 109 cases. Of the HGPIN cases, 13 (41.9%) expressed ERG immunostain. ERG expression in HGPIN was independent of patient age at presentation (P=0.4), pre-operative PSA (P=0.9), and the grade, using the novel Grade Groups (P=0.5). Conclusion: The frequency of HGPIN in our cohort appears similar to the one found in the Western patient populations and demonstrates a comparable frequency of ERG expression in these lesions.

Intra-thymic bronchogenic cyst an extremely rare tumor of anterior mediastinum in adults.

BACKGROUND: Intra-thymic bronchogenic cysts are a rare entity but should be considered in the differential of all non-invasive thymic masses. CASE PRESENTATION: We describe a 50-year-old patient who was found to have an incidental thymic mass on computer tomography of the chest. Non-invasive thymoma was suspected and a thoracoscopic thymectomy was performed. Final pathology revealed a bronchogenic cyst. CONCLUSION: Intra-thymic bronchogenic cysts are extremely rare tumors of the anterior mediastinum. It should be considered in differential diagnosis of anterior mediastinal masses.

Multiple Myeloma in a Patient with Focal Segmental Glomerulosclerosis: A Case Report.

BACKGROUND Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome in adults, which can be primary, or secondary to various causes. Unlike membranous nephropathy, FSGS is less likely to be associated with malignancy. Few cases have been reported of the occurrence of FSGS with hematological malignancies like multiple myeloma (MM). CASE REPORT A 48-year-old man presented with nephrotic syndrome and renal impairment and was diagnosed with primary FSGS after kidney biopsy, which showed a segmental scar with diffuse effacement of foot processes on electron microscopy. Treatment with steroids reduced proteinuria and stabilized the renal function. A few months later, the patient presented with acute Kidney Injury, bone pain, and anemia. A diagnosis of MM was made based on the bone marrow biopsy. Treatment of MM decreased proteinuria and improved renal function. CONCLUSIONS There is an association between FSGS and MM through an unclear mechanism.

Immune thrombocytopenia among patients with cancer and its response to treatment.

OBJECTIVES: The aim of this study was to determine the rate of immune thrombocytopenia (ITP) in adult Jordanian patients diagnosed with cancer, to correlate this rate with the type of cancer and to assess the response of ITP in patients with cancer to treatment. METHODS: All adult patients aged 16 years or older who had been diagnosed with cancer at King Abdullah University Hospital (KAUH) between September 2002 and October 2017 were included in this study. Their medical records were reviewed for the diagnosis of ITP. RESULTS: The total number of patients diagnosed with cancer at KAUH between September 2002 and October 2017 was 8318. The majority of patients had solid cancers (87.0%), and hematological cancers constituted 13%. Fifteen (0.2%) patients with cancer had ITP. ITP was significantly more common in patients with lymphomas (1.3%) than in patients with solid cancers (0.1%) (P < .005). In the multivariate analysis and after adjusting for age and gender, patients with lymphomas were 15.2 times more likely to be diagnosed with ITP than were patients with solid cancer. CONCLUSIONS: Patients with lymphomas had higher rates of ITP than did patients with solid cancers. Treatment of ITP-associated cancer may improve the platelets count.

Prostate cancer in Jordanian-Arab population: ERG status and relationship with clinicopathologic characteristics.

TMPRSS2/ERG fusion was found to be the most common genetic event in prostate adenocarcinoma. There is a strong correlation between the fusion and ERG-positive immunostaining. Many studies showed racial variation in ERG expression in prostate cancer patients. There is no data however on the rate of ERG-positive cancer in Jordanian or Arab population. We evaluated the frequency and the significance of ERG fusion in Jordanian-Arab population using immunohistochemistry for ERG. The cohort included 193 prostate cancer specimens: 109 needle core biopsies, 45 radical prostatectomies, 37 transurethral resections of prostate, and 2 enucleation specimens. We found ERG reactivity in 64 (33.2%) of evaluated cases. The observed ERG frequency in the Jordanian-Arab population is lower than the one documented in North America, but it is higher than in Asian patient cohorts. The ERG positivity was significantly associated with lower baseline prostate-specific antigen but was unrelated to patient age, Gleason Score, or the novel Gleason Grade Groups. In the 45 prostatectomy cases, ERG did not correlate with the pathologic stage, margin, nodal status, and the biochemical recurrence, and it did not appear to represent an important prognosticator.

Anaplastic Carcinoma Arising in a Mucinous Cystic Neoplasm Masquerading as Pancreatic Pseudocyst.

Mucinous cystic neoplasms (MCN) of the pancreas can vary from benign to premalignant and malignant. Preoperative diagnosis is essential to offer the patient appropriate treatment. Occasionally these cases may harbor anaplastic carcinoma while clinically masquerade as a pseudocyst. Here in, we report an unusual case of a 37-year old female presented with recurrent abdominal pain that was suspected clinically and by imaging studies to have a pseudocyst. EUS-FNA with internal drainage of the cyst was performed. Cytological evaluation of the cyst fluid showed numerous inflammatory cells composed mainly of many neutrophils admixed with macrophages reminiscent of the usual pseudocyst content but there were scattered rare dyscohesive malignant cells which were highly pleomorphic with multinucleation. Immunostains on the cell block showed immunoreactivity of these cells including the multinucleated cells for Cam 5.2 and AE1/AE3 and focally for Ber-Ep4, Moc -31, and CA19-9. The subsequent resection confirmed the presence of anaplastic (undifferentiated) carcinoma (AC) arising in a MCN of the pancreas. Diagn. Cytopathol. 2016;44:538-542. © 2016 Wiley Periodicals, Inc.

Not all gleason pattern 4 prostate cancers are created equal: A study of latent prostatic carcinomas in a cystoprostatectomy and autopsy series.

BACKGROUND: The Gleason grading system represents the cornerstone of the management of prostate cancer. Gleason grade 4 (G4) is a heterogeneous set of architectural patterns, each of which may reflect a distinct prognostic value. METHODS: We determined the prevalence of the various G4 architectural patterns and intraductal carcinoma (IDC) in latent prostate cancer in contemporary Russian (n = 220) and Japanese (n = 100) autopsy prostates and in cystoprostatectomy (CP) specimens (n = 248) collected in Italy. We studied the association of each G4 pattern with extraprostatic extension (EPE) and tumor volume to gain insight into their natural history. Presence of IDC and nine architectural features of Gleason grade 4 and 5 cancer were recorded. RESULTS: The prevalence of Gleason score ≥ 7 PC was higher in the autopsy series (11%) compared to the CP series (6.5%, P = 0.04). The prevalence of IDC and carcinoma with a cribriform architecture was 2.2% and 3.4% in the autopsy series and 0.8% and 3.6% in the cystoprostatectomy series, respectively. In multivariable analysis, cribriform architecture was significantly associated with increased tumor volume (P < 0.001) and EPE (OR:11.48, 95%CI:2.30-57.16, P = 0.003). IDC was also significantly associated with EPE (OR:10.08, 95%CI:1.58-64.28, P = 0.014). Small fused glands had a strong negative association with EPE in the autopsy series (OR:0.06, 95%CI:0.01-0.58, P = 0.015). DISCUSSION: Our study revealed that in latent prostate cancer both cribriform architecture and IDC are uniquely associated with poor pathological outcome features. In contrast, Gleason score 7 (3 + 4) cancers with small-fused gland pattern might possibly include some prostate cancers with a more indolent biology.

Prevalence of inflammation and benign prostatic hyperplasia on autopsy in Asian and Caucasian men.

UNLABELLED: Inflammation has been suggested to be involved in the pathogenesis of benign prostatic hyperplasia (BPH). We studied the prevalence of inflammation and BPH in Asian and Caucasian men on prostate glands (n=320) obtained during autopsy in Moscow, Russia (Caucasian men, n=220), and Tokyo, Japan (Asian men, n=100). We correlated the presence and grade of acute inflammation (AI) or chronic inflammation (CI) and BPH. AI, CI, and histologic BPH were analyzed in a blinded fashion using a grading system (0-3). We used the Cochran-Armitage test for associations between the degree of BPH and clinical variables and proportional odds logistic regression models in multivariable analysis. Histologic BPH was observed in a similar proportion of Asian and Caucasian men (p=0.94). CI was found in>70% of men in both the Asian and Caucasian groups (p>0.05). Higher BPH scores were associated with more CI (p<0.001). In multivariate analyses, individuals with CI were 6.8 times more likely to have a higher BPH score than individuals without (p<0.0001). Men included in this study presented at the hospital and their symptomatic status was not known. The prevalence of CI and BPH on autopsy is similar in Asian and Caucasian men despite very different diet and lifestyle. CI is strongly associated in both groups with BPH. PATIENT SUMMARY: In this study, we looked at the prevalence of inflammation and benign prostatic hyperplasia (BPH) on autopsy in Asian and Caucasian men. We found chronic inflammation in>70% of men on autopsy. More chronic inflammation was associated with more BPH.

Prevalence of prostate cancer on autopsy: cross-sectional study on unscreened Caucasian and Asian men.

BACKGROUND: Substantial geographical differences in prostate cancer (PCa) incidence and mortality exist, being lower among Asian (ASI) men compared with Caucasian (CAU) men. We prospectively compared PCa prevalence in CAU and ASI men from specific populations with low penetrance of prostate-specific antigen screening. METHODS: Prostate glands were prospectively obtained during autopsy from men who died from causes other than PCa in Moscow, Russia (CAU), and Tokyo, Japan (ASI). Prostates were removed en-block and analyzed in toto. We compared across the 2 populations PCa prevalence, number and Gleason score (GS) of tumour foci, pathological stage, spatial location, and tumor volume using χ(2), Mann-Whitney-Wilcoxon tests, and multiple logistic regression. All statistical tests were two-sided. RESULTS: Three hundred twenty prostates were collected, 220 from CAU men and 100 from ASI mean. The mean age was 62.5 in CAU men and 68.5 years in ASI men (P < .001). PCa prevalences of 37.3% in CAU men and 35.0% in ASI men were observed (P = .70). Average tumor volume was 0.303cm(3). In men aged greater than 60 years, PCa was observed in more than 40% of prostates, reaching nearly 60% in men aged greater than 80 years. GS 7 or greater cancers accounted for 23.1% and 51.4% of all PCa in CAU and ASI men, respectively, (P = .003). When adjusted for age and prostate weight, ASI men still had a greater probability of having GS 7 or greater PCa (P = .03). CONCLUSIONS: PCa is found on autopsy in a similar proportion of Russian and Japanese men. More than 50% of cancers in ASI and nearly 25% of cancers in CAU men have a GS of 7 or greater. Our results suggest that the definition of clinically insignificant PCa might be worth re-examining.

Diagnostic utility of androgen receptor expression in discriminating poorly differentiated urothelial and prostate carcinoma.

AIMS: Pathological separation of poorly differentiated urothelial and prostate carcinoma is difficult, but imperative because of the impact on patient management. Tumour morphology, in conjunction with a panel of immunohistochemistry (IHC), such as prostate-specific antigen (PSA), prostatic acid phosphatase (PSAP), CK7, CK20, p63 and high molecular weight keratins (HMWKs) are usually employed to resolve this issue. Androgen receptor (AR) expression is maintained in high-grade, undifferentiated prostate carcinoma, and thus, could be considered as a potentially useful adjunct to the conventional panel of markers. METHODS: We performed an institutional review of all cases from 2006 to 2012 in which AR IHC had been performed to determine its diagnostic utility in discriminating between poorly differentiated urothelial and prostate carcinoma. Of the eligible cases (n=40), there were 9 high-grade urothelial carcinomas, 27 prostate carcinomas and 4 with both prostate and bladder tumours. All diagnoses were made by integrating the clinical, radiological, morphological and IHC results. RESULTS: In all the prostate carcinomas, there was diffuse, intense nuclear staining for AR. The urothelial tumours were either negative, had cytoplasmic staining or showed occasionally weak nuclear staining. The difference was highly significant with p<0.0001 (Mann-Whitney U test). CONCLUSIONS: We conclude that AR is an important marker as it is best able to distinguish between poorly differentiated urothelial and prostate carcinoma. AR appears superior to PSA and PSAP, which are not consistently expressed in high-grade prostate carcinoma. Also, high-grade urothelial carcinoma may be negative for CK20, p63/HMWK and occasionally CK7. We advocate the inclusion of AR in the panel of markers to differentiate these tumours.