Juvenile Papillomatosis of the Breast: a Report of Two Cases with Review of the literature.

Background: Juvenile papillomatosis (JP) of the breast is a rare and benign proliferative disorder affecting young women. The affected patients tend to have an increased risk of breast cancer development during follow-up. Objective: This article aims to highlight a rare entity of breast disease, that harbor risk of breast cancer. Case Presentation: Here, we present 2 cases of JP in young females; the first case is a 13 year-old presented with spontaneous nipple discharge, while the other patient is a 24 year-old presented with a right breast lump. Both patients had a total excision of the breast lesions, revealing JP at histology. Discussion: Juvenile Papillomatosis is considered a clinicopathological entity and is usually misdiagnosed as fibroadenoma clinically and radiologically, which requires histological correlation. The histologic findings are well-defined (hyperplasia, papillomatosis, and multiple cysts with foamy histiocytes).The controversy in management between surgery and observation is because of insufficient knowledge about the direct relationship between JP and subsequent cancer. Conclusion: Considering the risk of developing breast cancer in JP, enrolling patients and their families in a close follow-up and surveillance program is crucial.

Interplay of Mendelian and polygenic risk factors in Arab breast cancer patients.

BACKGROUND: Breast cancer patients from the indigenous Arab population present much earlier than patients from Western countries and have traditionally been underrepresented in cancer genomics studies. The contribution of polygenic and Mendelian risk toward the earlier onset of breast cancer in the population remains elusive. METHODS: We performed low-pass whole genome sequencing (lpWGS) and whole-exome sequencing (WES) from 220 female breast cancer patients unselected for positive family history from the indigenous Arab population. Using publicly available resources, we imputed population-specific variants and calculated breast cancer burden-sensitive polygenic risk scores (PRS). Variant pathogenicity was also evaluated on exome variants with high coverage. RESULTS: Variants imputed from lpWGS showed high concordance with paired exome (median dosage correlation: 0.9459, Interquartile range: 0.9410-0.9490). After adjusting the PRS to the Arab population, we found significant associations between PRS performance in risk prediction and first-degree relative breast cancer history prediction (Spearman rho=0.43, p = 0.03), where breast cancer patients in the top PRS decile are 5.53 (95% CI 1.76-17.97, p = 0.003) times more likely also to have a first-degree relative diagnosed with breast cancer compared to those in the middle deciles. In addition, we found evidence for the genetic liability threshold model of breast cancer where among patients with a family history of breast cancer, pathogenic rare variant carriers had significantly lower PRS than non-carriers (p = 0.0205, Mann-Whitney U test) while for non-carriers every standard deviation increase in PRS corresponded to 4.52 years (95% CI 8.88-0.17, p = 0.042) earlier age of presentation. CONCLUSIONS: Overall, our study provides a framework to assess polygenic risk in an understudied population using lpWGS and identifies common variant risk as a factor independent of pathogenic variant carrier status for earlier age of onset of breast cancer among indigenous Arab breast cancer patients.

Adenomyoepithelioma of the breast with unusual confounding diagnostic feature: a case report.

BACKGROUND: Adenomyoepithelioma of the breast is an uncommon subtype of breast neoplasm that occurs in adults over a wide age range but most commonly in middle-aged and older adults. It usually presents as a solitary palpable mass or is detected on breast radiographic images. Histologically, it is a biphasic tumor with proliferation of both the epithelial and myoepithelial components of the glands, with variable types of tissue metaplasia. CASE PRESENTATION: A 64-year-old Saudi woman who underwent regular breast screening (mammogram) presented to our hospital following radiographic detection of a suspicious grouped microcalcification in the upper outer quadrant of her right breast on the mammogram. A wide local excision of the right breast lump was performed. Following histopathological examination of the breast lump, the final diagnosis was breast adenomyoepithelioma with mucoepidermoid/divergent differentiation, with no evidence of malignancy. About two years after the operation, a clinical follow-up conducted outside our hospital showed the development of ductal carcinoma in situ in the same breast. CONCLUSION: Although the prognosis and the plan of treatment remains the same, our case highlights the complexities in making an accurate diagnosis between the various types of metaplasia within adenomyoepithelioma on one hand and the presence of mucoepidermoid differentiation in adenomyoepithelioma on the other.

Breast biomarkers profile of invasive lobular carcinoma in a cohort of arab women shows no significant differences from carcinoma of no special type.

Objectives: Invasive lobular carcinoma (ILC) of the breast is known for its common presentation at an older age, and the frequent expression of favourable profile of estrogen and progesterone receptors (ER & PR) positivity, and human epidermal growth factor receptor 2 (HER2) negativity combined with low proliferation rate as measured by Ki67. This study aimed to test these clinicopathological features of ILC in an Arabic cohort. Methods: All breast biopsies diagnosed as IDC or ILC were retrospectively reviewed over 2 years period (2017-2018) in an academic centre. Variables were compared using Fisher's exact test for statistical significance. Results: A total of 134 cases were recruited, 12.7% were ILC. The median age was 52 years for both types. Clustering of ILC cases was noticed in luminal A subtype (47.1%), but there was no statistically significant difference in subtyping between the 2 histologic groups. Ki67 was significantly lower in ILC than IDC category. Conclusions: Our study showed that ILC in our cohort lacks the advantage of older age and the common high expression of ER positivity in comparison to IDC. There is, however, significant difference of the value of Ki67 proliferation marker. The prognosis of lobular morphology is questionable in our cohort.

The accuracy of nipple discharge cytology in detecting breast cancer.

OBJECTIVES: This study aimed to disclose the importance of nipple discharge (ND) and the accuracy of its economic and fast cytological interpretation. METHODS: All ND cytology cases for Saudi patients done between 2004 and 2013 were retrieved from the Pathology e-system. Only cases that have subsequent tissue diagnoses were included in this study (n = 228). Age and bloody nature of the ND were both tested for association with a higher chance of carcinoma. Diagnostic accuracy of ND cytology was calculated twice, including and excluding the "atypical" cases. RESULTS: Specificity and positive predictive value were 100% for ND cytology in both cases. Sensitivity (34.6%; 52.9%), negative predictive value (93.15 %; 96.1%), false-negative rate (65.4%; 47.1%), accuracy rate (93.4%; 96.2%), when atypical cases were included and excluded; respectively. Only 10.5% of the patients complaining from nipple discharge had breast cancer. For those who had cancer, nipple discharge cytology was positive and showed the cancer cells in only 37.5%, while the rest were false negative. Bloody ND disclosed a significant association with malignancy (p < 0.001), but the association was statistically not significant for old age (p = 0.062). CONCLUSIONS: The prospect of having breast cancer with the presentation of ND is low, and it can be missed by studying the ND cytology alone in a high proportion of cases. Excluding the atypical category did not make a significant improvement in the test's accuracy.

Histopathologic and Autopsy Findings in Patients Diagnosed With Coronavirus Disease 2019 (COVID-19): What We Know So Far Based on Correlation With Clinical, Morphologic and Pathobiological Aspects.

In response to the current outbreak of Coronavirus Disease-2019 (COVID-19), a fast body of literature emerged providing insights into the clinical and radiologic aspects of the novel disease, while the pathologic manifestations on tissue are yet to be sufficiently characterized mainly due to paucity of autopsy and biopsy of these cases. It is essential for both the clinicians and pathologists to maintain up-to-date knowledge of this continuously evolving topic in the midst of the current pandemic. Besides, understanding the impact of any disease in tissue pathology is crucial for better analysis of the pathogenesis and speculation of potential therapeutic targets. This review aimed to highlight the potential implication of COVID-19 in the pathology of various organ systems. We discuss the pathologic findings of the lungs, gastrointestinal tract, liver, brain, kidneys, heart, and the reproductive and immune systems that are associated with COVID-19. It seems that the respiratory, immune, and the digestive systems are the major targets of the disease. Mild mononuclear inflammatory cell infiltration is the most frequent histologic finding in general. Besides organ-specific changes, microthrombi, especially noticed in lungs, kidneys, and prostates, are the most significant observation microscopically. In addition, the possible mechanisms of organ injury were also reviewed.

Undergraduate medical students' perception of pathology.

With the current trend of internationalization of medical school curricula, pathology role tends to gradually shrink. This potentially could negatively influence the students' decisions of selecting pathology as their prospective career. Besides, a pathology-related knowledge gap might be created as a side effect. In 2013, the College of Medicine in Imam Abdulrahman Bin Faisal University launched a new curriculum adopted from Monash University in Australia. Consequently, the pathology time was compromised to be 72 instead of 138 h in total. This study was planned to investigate the students' perspective of pathology that address the aforementioned concerns. A survey was distributed among the targeted participants. The response rate was 90.4%. While 8.7% of the students considered pathology as a possible prospect clerkship program, only 2 students elected it as their first option. Out of 230 participants who either chose not to consider pathology or were not sure to consider it or not, 172 declared their reasons. For almost half of them the cause was another favored specialty. The vast majority of students chose traditional lectures as their preferred way of learning. Twenty-six and 85 students identified themselves as either not aware or not sure if they discern the exact role of pathologists in clinical care; respectively. While 86.6% of the students think that providing relevant clinical data and differential diagnoses is necessary for the pathologists as they are not pure morphologists, only 13.4% of the cohort were aware of the indications of intra-operative consultations. In conclusion, the majority of students selected lectures as the preferred way of learning, but their responses regarding their knowledge of the exact role of pathologists, and the indications of intra-operative consultations, as well as their response toward considering pathology as future career all are implicit for combining hands on, active learning along with the passive lectures.

The accuracy of endometrial sampling for the diagnosis of patterns of endometrial pathology in women presenting with abnormal uterine bleeding. More conservative therapeutic approaches.

OBJECTIVES: Abnormal uterine bleeding (AUB) is a leading cause of hysterectomies, the cause of which is usually diagnosed with preoperative endometrial sampling. We planned this study to assess the accuracy of diagnosing the histologic patterns of endometrium in the preoperative sample in reference to the final histologic diagnosis in hysterectomy. METHODS: We retrospectively reviewed medical charts between January 2011 and December 2015 at a tertiary hospital in Saudi Arabia and identified 43 cases of AUB with complete documentation. The histologic diagnoses were classified into normal and benign pathology group (N/B), or carcinoma and hyperplasia category (Ca/H). Measures of validity were used to compare endometrial sampling histological diagnoses to diagnoses following hysterectomy and Cohen's kappa to assess for agreement between the 2 modalities. Results: The median age of all patients was 49 years. Preoperative histologic examination showed 53.8% sensitivity, 90% specificity, 70% positive predictive values and 81.8% negative predictive values, 30.1%  false positive rates and 18.2% false negative rates. The agreement between preoperative and postoperative histologic diagnoses was moderate (79.1%, k=0.469). Conclusion: The accuracy of preoperative histologic examination was moderate. Our findings recommend cautious clinical decision making and limiting hysterectomy to women who do not respond to other therapeutic measures.

A Case of Trigeminal Schwannoma Presenting as a Parasellar Mass.

Schwannoma's of considerable size arising from the trigeminal nerve are very rare. Here, a case of a large right-sided parasellar mass diagnosed as a trigeminal schwannoma is reported. Complete resection of the tumor was successfully achieved. The patient had an excellent postoperative course.

The updated grading system of prostate carcinoma: an inter-observer agreement study among general pathologists in an academic practice.

In 2016, the grading criteria for Gleason scoring (GS) have been updated in the WHO classification of tumors of the prostate, and a new set of grade groups (GG) was introduced. As the inter-observer discordance is a well-known concern in Gleason grading before the update and no reproducibility study testing the grade groups exists, we planned to evaluate the inter-observer agreement of the most updated grading system. Four pathologists assessed 126 cores of prostatic carcinoma, and Kappa (k) test was calculated. The agreements for both GS and GG were substantial (k = 0.753 and 0.752; respectively). Discerning GG 2 from 3 also attained reasonable outcome (k = 0.675). Based on our results, the updated grading system seems to be reproducible, with satisfactory inter-observer concordance rate.

Chondroid lipoma associated with osteoclast-like multinucleated giant cells - a case report.

Chondroid lipoma is a rare soft tissue neoplasm. We report case of chondroid lipoma associated with osteoclast-like multinucleated giant cells. To the best of our knowledge, the presence of these giant cells has not been previously described in the English literature. The recognition of these cells is important and their occurrence in this rare neoplasm should not mislead the pathologist to misdiagnose this entity.

Histologic factors predicting invasion in patients with ductal carcinoma in situ (DCIS) in the preoperative core biopsy.

BACKGROUND: It is desirable to decrease the underestimation rate of invasion in cases diagnosed as ductal carcinoma in situ (DCIS) in breast core needle biopsy (CNB) in order to determine the appropriate candidates for axillary staging. The objective of this study is to identify the predictors of invasion in histology. METHODS AND RESULTS: Consecutive 92 CNB's were retrospectively evaluated. The upstaging rate was 47.8% after surgery. Among all the evaluated parameters, high nuclear grade, single architectural pattern, marked periductal lymphocytic infiltration, partial myoepithelial loss and the presence of foci suspicious of microinvasion were the significant predictors of invasion (two tailed p values 0.0327, 0.0003, 0.0346, <0.0001, 0.0025; respectively). Variables that didn't show significant upstaging include: comedo necrosis, microcalcification, periductal fibrosis, various architectural patterns, tumor attenuation, and the immunophenotype. Previous studies were also reviewed. CONCLUSIONS: We identified 5 predictive factors of upstaging. The lack of standardized quantification method may account, at least partially, for the conflicting results in different studies. To overcome this, we suggested a comprehensive reporting template for DCIS identified in CNB.

The Performance of Ki-67 Labeling Index in Different Specimen Categories of Invasive Ductal Carcinoma of the Breast Using 2 Scoring Methods.

In breast carcinoma proliferative rate is not only prognostic, but also predictive factor. Ki-67 labeling index (Ki-67 LI) is a superior and more reproducible way to assess proliferation than counting mitoses. There are different Ki-67 LI cut-off values proposed for stratification. The best method of scoring Ki-67 LI is still controversial. Our aim was to test the consensus of Ki-67 LI read in the 2 most common specimens, diagnostic core biopsies (CNB) and surgical excision (SE), first using the hot spot (HS) for counting, and then the average (Av) Ki-67 LI. Cases diagnosed as having invasive duct breast carcinoma on CNB followed by SE over 6 years were recruited (n=96). Ki-67 LI was counted in both specimen types using HS and Av scoring methods. For both methods, agreement between the 2 specimen categories was tested using different cut-off values. Intraobserver reproducibility was also measured for both scoring methods. Ki-67 LI was significantly lower in CNBs compared with SEs (mean difference: -13.3 and -6.3, P<0.001, using HS and Av methods, respectively). The agreement between Ki-67 LI in CNBs and SEs using 10, 14, and 20 as cut-off value was superior when we used Av method (for κ=0.793, 0.814, and 0.745; vs. for HS: κ=0.542, 0.525, and 0.672, respectively). Intraobserver reproducibility ranged from very good to perfect for both methods. Our results suggested that specimen-specific cut-off value should be applied for both scoring methods.

Adult Desmoplastic Medulloblastoma.

Medulloblastoma is more common in young age and rare in adult age. Some characteristics that characterize medulloblastoma in adults compared with children: Lateral cerebellar location, heterogeneous signal intensity on magnetic resonance imaging, desmoplastic histological variant and more favorable prognosis. Preoperative diagnosis is important for correct management of these patients. However, because of the low incidence of medulloblastoma in adults, preoperative diagnosis still challenging and prognostic factors and best treatment options are still controversial. We report a case of a 31-year-old male patient who presented with a rare case of posterior fossa medulloblastoma.

Combined Use of Unguided FNA and CNB Increases the Diagnostic Accuracy for Palpable Breast Lesions.

BACKGROUND: Obtaining nonsurgical precise diagnosis of a palpable breast lesion is of paramount importance. Both core needle biopsy (CNB) and fine needle aspiration (FNA) are validated techniques used for this purpose. In this study, we compared the accuracy of both methods and explored whether combining both tests adds significant diagnostic value, and for the first time, we tested the concordance of tumor grading in parallel biopsies with reference to surgical excision (SE). METHODS: Patients underwent concurrent unguided FNA and CNB followed by SE were retrospectively recruited. Chi-square was used to compare the accuracy of malignancy detection, and tumor grade agreement was calculated using kappa (k) statistical test with reference to SE findings. RESULTS: All patients were females (n: 170). The median age was 45 years. Excluding 18 cases which had inadequate FNA, accuracy of FNA and CNB was 86.2% and 79.6%; respectively. Accuracy was 94.1% when we considered both tests together for any positive result. For tumor grading, the agreement was 91.6% for CNB and 98.8% for FNA. CONCLUSION: Diagnostic strength was comparable for both FNA and CNB, slightly more favorable for the former. Combination of both tests significantly minimized missing cases as false negative. When available, it is worthy to grade malignant FNA samples. Diagn. Cytopathol. 2016;44:578-581. © 2016 Wiley Periodicals, Inc.

Psammomatoid Ossifying Fibroma of the Ethmoid Sinus with Secondary Intracranial Aneurymal Bone Cyst: A Case Report and Literature Review.

Juvenile psammomatoid ossifying fibroma (JPOF) is a rare, slowly progressive tumor of the extragnathic craniofacial bones, with a tendency toward locally aggressive behavior and recurrence. The pathognomonic histopathologic feature is the presence of spherical ossicles, which are similar to psammoma bodies. Very few cases in association with secondary aneurysmal bone cyst (ABC) formation have been reported in literature. Treatment consists of complete surgical removal. However, incomplete excision has been associated with a high local recurrence rate. The prognosis is good because malignant change and metastasis have not been reported. The authors are reporting a case of JPOF of the ethmoid bones with secondary ABC in a 7-year-old female patient.

Prostatic diseases under focus in a university hospital in Eastern Saudi Arabia. A 15-year experience.

OBJECTIVES: To explore the spectrum of pathologies diagnosed in prostatic biopsies of Saudi men, and test whether the frequency of diagnosing the malignant fraction has been changed over the last 15 years, and assess the association between chronic inflammation (CI) with both benign prostatic hyperplasia (BPH) and cancer (PCa), and investigate the histological findings of cases presented with acute urinary retention (AUR) clinically. METHODS: This is a retrospective cohort study including all prostatic biopsies accessed in the files in the Surgical Pathology Laboratory of King Fahd University Hospital, Alkhobar, Kingdom of Saudi Arabia over 15 years (1999-2013) for Saudi men. Age, procedure indication, and final diagnoses were retrieved and slides were reviewed. RESULTS: There were 360 cases included in this study with a median age of 65 year-old. The BPH comprised the most (64.7%), while PCa accounted for 89 cases, 13.5% of which were incidental. Most cases of both BPH and PCa were diagnosed in the seventh decade. The frequency of diagnosing PCa did not show a solid rise or fall over time. Chronic inflammation is more related to BPH than to PCa. Only CI showed a significant statistical association with AUR. CONCLUSION: Prostatic diseases show a stable trend over time. While CI is a common dominator for both BPH and PCa, it is associated more with BPH. Among all histological findings, only CI is related to the clinical presentation of AUR.

Primary gastric actinomycosis: report of a case diagnosed in a gastroscopic biopsy.

BACKGROUND: Primary gastric actinomycosis is extremely rare, the appendix and ileocecal region being the most commonly involved sites in abdominopelvic actinomycosis. Herein, we report a case of primary gastric actinomycosis. The diagnosis was made on microscopic evaluation of gastroscopic biopsy specimens. To the best of our knowledge, this is the third case to be reported in the literature, in which the diagnosis was made in a gastroscopic biopsy rather than a resection specimen. CASE PRESENTATION: An 87-year-old Saudi male on medication for cardiomyopathy, premature ventricular contractions, renal impairment, hypertension, and dyslipidemia, presented to the emergency department with acute diffuse abdominal pain, abdominal distension, constipation and vomiting for two days, with no history of fever, abdominal surgery or trauma. The patient was admitted to the hospital with an impression of gastric outlet obstruction. Based on radiologic and gastroscopic findings, a non-infectious etiology was suspected, possibly adenocarcinoma or lymphoma. Gastroscopic biopsies showed an actively inflamed, focally ulcerated atrophic fundic mucosa along with fragments of a fibrinopurulent exudate containing brownish, iron negative pigment and abundant filamentous bacteria, morphologically consistent with Actinomyces. CONCLUSION: Althuogh extremely rare, primary gastric actinomycosis should be considered in the differential diagnosis of radiologic and gastroscopic diffuse gastric wall thickening and submucosal tumor-like or infiltrative lesions, particularly in patients with history of abdominal surgery or trauma, or those receiving extensive medication. A high level of suspicion is required by the pathologist to achieve diagnosis in gastroscopic biopsies. Subtle changes such as the presence of a pigmented inflammatory exudate should alert the pathologist to perform appropriate special stains to reveal the causative organism.