Prostatic tissue: an unexpected finding in a mature ovarian teratoma : Case report and systematic literature review.

PURPOSE: Prostatic tissue in an ovarian teratoma is an unusual finding, whose initiation in a 46, XX karyotype tissue is yet to be clarified. We present a case from our files and review the literature for this intriguing finding. METHODS: Unstained histology sections of the ovarian teratoma containing prostatic tissue were evaluated using immunohistochemistry for PSA and androgen receptor. RESULTS: Both PSA and androgen receptor immunostainings were positive in the prostatic tissue. From the literature review, it appears that most of the patients (74%) with similar findings were either pregnant or experiencing a miscarriage, menopausal or infertile at presentation, showing that an imbalanced hormone status is frequently associated with the presence of male structures in ovarian teratomas.

Exploring Mitochondrial Localization of SARS-CoV-2 RNA by Padlock Assay: A Pilot Study in Human Placenta.

The ongoing COVID-19 pandemic dictated new priorities in biomedicine research. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is a single-stranded positive-sense RNA virus. In this pilot study, we optimized our padlock assay to visualize genomic and subgenomic regions using formalin-fixed paraffin-embedded placental samples obtained from a confirmed case of COVID-19. SARS-CoV-2 RNA was localized in trophoblastic cells. We also checked the presence of the virion by immunolocalization of its glycoprotein spike. In addition, we imaged mitochondria of placental villi keeping in mind that the mitochondrion has been suggested as a potential residence of the SARS-CoV-2 genome. We observed a substantial overlapping of SARS-CoV-2 RNA and mitochondria in trophoblastic cells. This intriguing linkage correlated with an aberrant mitochondrial network. Overall, to the best of our knowledge, this is the first study that provides evidence of colocalization of the SARS-CoV-2 genome and mitochondria in SARS-CoV-2 infected tissue. These findings also support the notion that SARS-CoV-2 infection can reprogram mitochondrial activity in the highly specialized maternal-fetal interface.

Zero-ischemia testis-sparing surgery for probably benign pediatric testicular tumors.

Permanent ischemia-induced testicular damage may occur as early as 30 min in prepupertal rats. With the goal of potentially enhancing testicular function and fertility preservation, we performed testis-sparing surgery (TSS) without ischemia for testicular lesions in select children with negative markers and high likelihood of benignity on ultrasonography. Preliminary experience suggests that off-clamp TSS should be more liberally encouraged, especially in infants and prepubertal children, given their particularly vulnerable spermatic cord elements.

Primary anaplastic large T-cell lymphoma of the psoas muscle.

Lymphomas presenting and mimicking soft-tissue masses are important to recognize, to avoid unnecessary treatment delays or extensive surgery. We describe a case of primary anaplastic large cell lymphoma (ALCL) arising from a deep skeletal muscle in a middle-aged male. He presented with a two-month history of swelling of his right thigh and mild fever, which led to a diagnosis of abscess formation. Antibiotics were prescribed for two weeks, with little improvement of symptoms. Subsequently, an exploratory surgery, with excision of the mass, demonstrated a ALCL of the psoas muscle, ALK-1 positive.

Metastases to extraocular muscles from breast cancer: case report and up-to-date review of the literature.

BACKGROUND: Unilateral or bilateral metastases to extraocular muscles are very rare in breast cancer. CASE PRESENTATION: We describe a case of inferior rectus extraocular muscle involved by ductal luminal B/Her-2 neu negative breast cancer, observed in a cohort of 580 patients. Our patient had received chemotherapy and hormonal therapy (tamoxifen for 3 years and letrozole in the following 3 years) for her primary cancer and developed an orbital metastasis while she was under aromatase inhibitor-based therapy. Diagnosis was confirmed by MRI and biopsy. Orbital radiotherapy, combined with fulvestrant, resulted in shrinking of the secondary mass. A third line hormonal therapy using palbociclib was then started. Twelve-months later, MRI showed no residual tumor mass. Currently, the patient is alive and in good general conditions after 20 months. CONCLUSIONS: Literature review yielded 57 patients with extraocular muscle metastases from breast cancer, mostly due to the invasive lobular subtype of carcinoma. In addition to the present case, only 4 other extraocular muscles metastases from invasive ductal carcinoma has been reported, pointing out to the rarity of ductal type spread to the orbit in the natural history of breast cancer. Surgery may be used as a single treatment, despite no improvement of symptoms. Radiotherapy alone or combined with chemotherapy, or with chemotherapy plus hormonal therapy are available options. Results are, however, missing or poor. The present case is the first one with complete and stable response after 20 months to radiotherapy, antiestrogen drug fulvestrant and selective inhibitor of CDK4 /CDK6 palbociclib. In this subset of patients, with unusual metastatic sites and frequent multi-organ metastatic impairment, a multidisciplinary approach is indicated in order to achieve the best therapeutic management and long-term surveillance.

Impact of Hormone Receptor Status and Ki-67 Expression on Disease-Free Survival in Patients Affected by High-risk Endometrial Cancer.

OBJECTIVES: The aim of this study was to evaluate the immunohistochemical (IHC) expression of Ki-67, estrogen receptors α (ERsα), and progesterone receptors (PRs) in high-risk endometrial cancer patients and to assess their prognostic impact. METHODS/MATERIALS: Immunohistochemical expression of Ki-67, ERsα, and PRs was evaluated in primary untreated endometrial cancer. The correlation among IHC staining and risk factors of recurrence such as age, Federation International of Gynecology and Obstetrics stage, grading, depth of invasion, and metastatic spread was assessed. RESULTS: Eighty-two patients were available for the analysis. Mean ± SD age was 65.05 ± 10.48 years. The IHC assessment revealed a lack of ERα in 46.3% and of PR in 48.7% as well as a high Ki-67 in 31.7%. Loss of ERα and PR was associated with a significant higher rate of advanced stage of disease, a higher frequency of G3 tumors, and a myometrial invasion greater than 50%. A strong Ki-67 expression correlated with a deeper myometrial invasion. Analysis of the interrelationship between receptor immunonegativity revealed a relevant association of ERα immunolocalization with PR and with a high Ki-67 expression. The present study also showed that loss of ERα (P = 0.003), advanced Federation International of Gynecology and Obstetrics stage (P < 0.001), and high Ki-67 (P = 0.004) were independent prognostic factors of a shorter disease-free survival. Importantly, loss of ERα, loss of PR, and a high Ki-67 were correlated with a higher incidence of distant recurrence. CONCLUSIONS: A systematic immunohistochemistry should be a key step in the therapeutic algorithm and could contribute to the identification of high-risk tumors.

Breast cancer or metastasis? An unusual case of metastatic malignant pleural mesothelioma to the breast.

BACKGROUND: Metastases to the breast from extramammary malignancies are very rare, and ruling out the diagnosis of primary breast tumor is important in order to decide on clinical management and predict prognosis. CASE PRESENTATION: Clinical examination revealed in a 49-year-old hairdresser a 3-cm hard lump adherent to the underlying layers in the right breast. Trucut biopsy was performed. Histology showed a solid proliferation of medium-sized neoplastic polygonal cells. Immunohistochemical analysis showed tumor cells diffusely positive for cytokeratin 8/18 and calretinin and focally positive for cytokeratin 5/6 and Wilms' tumor 1, e-cadherin, and human bone marrow endothelial-1. Estrogen receptors and progesterone receptors were negative. The final diagnosis was metastatic epithelioid malignant pleural mesothelioma. CONCLUSIONS: Immunohistochemistry is an important tool for a conclusive diagnosis of malignant pleural mesothelioma. Owing to the degree of histological and immunohistochemical overlap, a high level of clinical suspicion is essential in order to avoid unnecessary mutilating surgery.

CX3CL1 and CX3CR1 expression in tertiary lymphoid structures in salivary gland infiltrates: fractalkine contribution to lymphoid neogenesis in Sjogren's syndrome.

OBJECTIVES: Primary SS is an autoimmune disease characterized by chronic lymphocytic inflammation and ectopic germinal centre (GC) formation within salivary glands. Fractalkine (CX3CL1), associated with the pathogenesis of RA, is the sole member of the CX3C chemokine (CK) family and acts as an adhesion and chemotactic molecule. The objectives of this work are to determine to what extent CX3CL1 and its receptor CX3CR1 expression might be altered in salivary glands obtained from patients and to establish whether these CKs might be involved in SS ectopic lymphoneogenesis. METHODS: We assessed the presence of CX3CL1 protein in sera by ELISA in 21 patients with primary SS, 11 patients with Sicca syndrome (Sicca), 20 RA patients and 10 blood donors. Histological evaluation was performed on sequential sections of salivary gland tissue. Using TaqMan RT-PCR we studied CX3CL1 and CX3CR1 mRNA expression in salivary gland tissues from a molecular point of view. RESULTS: Increased serum levels of CX3CL1 protein were observed in SS patients compared with controls (P < 0.0001) and in RA patients compared with controls (P < 0.0001), but no difference was found between Sicca patients and controls (P = 0.22). We identified histologically the cells expressing CX3CL1 and CX3CR1 in salivary glands of SS patients and we localized the molecule within tertiary lymphoid structures. Finally, the mRNA levels of the CK and its receptor were up-regulated in SS salivary glands. CONCLUSION: We believe that our findings point to the need for future studies on CX3CL1 and CX3CR1 proteins as contributors to the formation of ectopic GCs and possibly as a new tool in the evaluation and diagnosis of SS.

May increased CA125 in borderline ovarian tumor be indicative of a poor prognosis? A case report.

We present a case of a 58-year-old menopausal woman referred to our hospital for the presence of large pelvic masses diagnosed by clinical examination and pelvic ultrasound. MRI examination showed voluminous bilateral capsulated multilocular ovarian cysts slightly hyperintense on T1-weighted images with thick septa and small papillary projections. CT scan confirmed the MRI findings. Among the ovarian tumor markers analyzed (CA125, HE4, and CA72.4), only Ca125 was slightly increased (48 U/ml). These data were suggestive of mucinous ovarian tumor. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, appendectomy, and multiple peritoneal biopsies. Pathological examination revealed bilateral borderline mucinous ovarian tumor with superficial atypical implants. Nine months later, the patient complained of left coxofemoral pain and underwent a PET/TC total body that suggested pubic bone metastases. Ovarian tumor markers were analyzed, and a second PET/TC was performed. CA125 was 252 U/ml, HE4 62 pM/L, and CA72.4 > 100 U/Ml. PET/TC was suggestive of peritoneal carcinosis. The patient was readmitted to the hospital. Clinical examination revealed small vaginal nodules. All nodules were excised. Microscopic analysis of all specimens revealed metastatic mucinous adenocarcinoma of intestinal type.The case shows that even a slight CA125 increase in the presence of a borderline ovarian tumor should not be overlooked since it can be indicative of a progressive disease. This case also highlights its additional diagnostic value when serum CA125 analysis is used in conjunction with MRI and CT imaging for the prognosis of mucinous borderline ovarian tumors (mBOTs).

Benign schwannoma in supraclavicular region: a false-positive lymph node recurrence of breast cancer suspected by PET scan.

INTRODUCTION: Positron emission tomography (PET) is the most accurate imaging modalities to detect malignancies. And it helps to take decisions regarding diagnosis, staging, recurrence, and therapeutical management. CASE PRESENTATION: We report a case of a suspected supraclavicular lymph node relapse, diagnosed by PET-CT in a breast cancer patient. The lymph node was surgically removed in outpatient with local anesthesia. Histological findings diagnosed a benign Schwannoma. In this patient PET-CT failed to distinguish benign tumors from metastatic supraclavicular lymph nodes. CONCLUSION: This case confirms the need to investigate histologically suspected supraclavicular lesions, during breast cancer follow up.

A solitary fibrous tumour of the eyelid.

OBJECTIVE: To report a case of palpebral solitary fibrous tumour (SFT). CLINICAL PRESENTATION AND INTERVENTION: An elderly man presented with a slow-growing painless mass in the lower conjunctival fornix in the left eye. The lesion was excised and it measured 0.9 cm in maximum diameter. The microscopic features were characteristic of a benign SFT, with immunohistochemical reactivity for vimentin, CD34 and Bcl-2 protein. Nuclear staining for progesterone receptor was also observed. CONCLUSION: This tumour displayed a benign course, with no recurrence after excision. CD34 immunohistochemistry proved to be a useful adjunct to the microscopic diagnosis.

Ciliated Cells in Renal Calyx mucosa: Metaplastic Change or Developmental Abnormality? Immunohistochemical Study of one Case and Review of the Literature.

Ciliated epithelial cells have been rarely observed in urothelium lined mucosa. Only extremely rare reports in the literature have described this phenomenon and no cases have been described in other sites than the male urethra. Herein, we illustrate the finding of ciliated pseudostratified columnar cells in the renal calyx mucosa adjacent to an area of urothelial invasive carcinoma in an 82 year-old man with previous history of nephrolithiasis. The ciliated cells covered a linear extension of 0.5 cm: they were positive for keratin 7 and keratin 8/18 and negative for keratin 20. Alcian blue staining was positive in some vacuoles in the apical cytoplasm of the same cells whereas PAS (Periodic Acid-Schiff) staining was negative. GATA3 resulted negative in ciliated cells except for a layer in the basal portion of the epithelium, just above the basal membrane. The actual prevalence of ciliated epithelia in the urinary tract is not well documented and the current knowledge on the subject is limited to electron scanning microscopy studies. The significance of this phenomenon remains unknown: it could be either a developmental abnormality or more probably a metaplastic change. Associated urolithiasis, which has been described in both a previous report and in the present one, could hypothetically represent a possible trigger for this unusual cell change. However, this hypothesis needs to be confirmed through further investigation.

Is Gastric Involvement by Strongyloides stercoralis in an Immunocompetent Patient a Common Finding? A Case Report and Review of the Literature.

PURPOSE: Gastric infection with Strongyloides stercoralis (SS) usually occurs in immunocompromised patients. The unexpected observation of this parasite in an otherwise healthy young lady who had undergone upper endoscopy and biopsy sampling of the gastro-duodenal mucosa, prompted us to review the literature to ascertain the conditions favouring gastric colonization by SS. METHODS: Pathology files of gastroduodenal biopsies received at St. Mary's hospital, Northern Uganda, between 2007 and 2017 were reviewed. Pubmed search was performed under the headings "Strongyloides stercoralis", "Gastric parasitosis". RESULTS: Histology of the only gastroduodenal biopsy with SS infection showed parasite eggs, immature rhabditiform larvae, and numerous adult worms in gastric pits and rhabditiform larvae in interepithelial parasitic tunnels, causing reactive changes of the glandular epithelium. There was no significant acute inflammatory cell infiltrate surrounding the parasites. Literature review showed that gastric SS infection appears to be very uncommon and was, as expected, largely prevalent in immunodeficient individuals (84.2% of published cases). The rare gastric SS infection is a complication of systemic strongyloidiasis, either hyperinfective, or disseminated form. It is also commonly associated with duodenal infection at microscopical examination. CONCLUSION: Involvement of gastric mucosa in the absence of duodenal strongyloidiasis appears to be quite rare and false-negative histopathological exams are reported if only the stomach is biopsied.

In Vivo Comparison of Micro-Balloon Interventions (MBI) Advantage: A Retrospective Cohort Study of DEB-TACE Versus b-TACE and of SIRT Versus b-SIRT.

PURPOSE: The purpose of this study was to evaluate in vivo the role of the micro-balloon by comparing trans-arterial chemoembolization (DEB-TACE) and selective internal radiotherapy (SIRT) procedures performed with and without balloon micro-catheter (b-DEB-TACE and DEB-TACE/SIRT and b-SIRT) for the treatment of hepatocellular carcinoma (HCC). METHODS: The impact of a balloon micro-catheter on trans-arterial loco-regional treatment was analyzed using non-enhanced post-procedural cone-beam CT (Ne-CBCT) by comparing the attenuation values in the embolized area and the surrounding liver tissue before and after DEB-TACE versus b-DEB-TACE and by comparing 2D/3D dosimetry in single-photon emission computed tomography after SIRT versus b-SIRT, and by comparing the histological count of the beads following orthotopic liver transplantation in the DEB-TACE versus b-DEB-TACE subgroup. RESULTS: We treated 84 HCC patients using trans-arterial loco-regional therapy. Fifty-three patients (26 DEB-TACE and 27 b-DEB-TACE) were analyzed in the TACE group. Contrast, signal-to-noise ratio, and contrast-to-noise ratio were all significantly higher in b-DEB-TACE subgroup than DEB-TACE (182.33 HU [CI95% 160.3-273.5] vs. 124 HU [CI95% 80.6-163.6]; 8.3 [CI95% 5.7-10.1] vs. 4.5 [CI95% 3.7-6.0]; 6.9 [CI95% 4.3-7.8] vs. 3.1 [CI95% 2.2-5.0] p < 0.05). Thirty-one patients (24 SIRT and 7 b-SIRT) were analyzed in the SIRT group. 2D dosimetry profile evaluation showed an activity intensity peak significantly higher in the b-SIRT than in the SIRT subgroup (987.5 ± 393.8 vs. 567.7 ± 302.2, p = 0.005). Regarding 3D dose analysis, the mean dose administered to the treated lesions was significantly higher in the b-SIRT than in the SIRT group (151.6 Gy ± 53.2 vs. 100.1 Gy ± 43.4, p = 0.01). In histological explanted liver analysis, there was a trend for higher intra-tumoral localization of embolic microspheres for b-DEB-TACE in comparison with DEB-TACE. CONCLUSIONS: Due to the use of three different methods, the results of this study demonstrate in vivo, a better embolization profile of oncological intra-arterial interventions performed with balloon micro-catheter regardless of the embolic agent employed.

Psychophysical and electrophysiological testing in ocular hypertension.

PURPOSE: The purpose of this study was to compare psychophysical and electrophysiological testings in early optic nerve dysfunction in a group of clinically asymptomatic subjects with suspect ocular hypertension (OHT). METHODS: Forty eyes of 40 patients with suspect OHT and asymmetrical horizontal cup/disc ratio (0.2/0.4), 22 eyes of 22 patients with open-angle glaucoma (OAG), and 40 eyes of 40 healthy controls were evaluated by using frequency-doubling technology perimetry (FDT), contrast sensitivity (CS), pattern electroretinography (PERG), and pattern visual-evoked potentials (VEP). The VEP were elicited by checkerboard stimuli with large (VEP 120), medium (VEP 45), and small (VEP 15) checks; then the values of the amplitude (A) and latency (L) of P100 peaks were studied. Receiver operator characteristic (ROC) curves were calculated to determine the sensitivity, specificity, and optimal cutoff points of abnormal values. A logistic regression analysis was performed to determine which tests were providing the most useful information. In addition, Kruskal-Wallis test was performed to test the differences between the control group and the OHT group. RESULTS: VEP P100 peak latency (VEP L15 and VEP L45) and amplitude (VEP A120), PERG N95 peak amplitude, CS at medium spatial frequencies (CS 4SF), and FDT pattern standard deviation (PSD) yielded the greatest sensitivity (85.0 to 60.0%) and specificity (80.0 to 60.0%) ratio, displaying the largest ROC curve areas; whereas PERG N95 peak latency ROC curve had the smallest areas. Kruskal-Wallis test showed that most diagnostic tests were able to differentiate the OHT group from the control group. Stepwise logistic regression analysis identified VEP L15 (p < 0.001), CS 4SF (p = 0.023), FDT PSD (p = 0.032), and VEP A120 (p = 0.072) as tests that could be useful to distinguish controls from OHT. CONCLUSIONS: Our data confirm that psychophysical and electrophysiological tests are useful for early detection of patients at risk of developing OAG.

Incidence of male breast carcinoma in North Uganda: A survey at Lacor Hospital, Gulu, during 2009-2016.

BACKGROUND: Little information is available on male breast cancer (MBC) incidence from sub-Saharan Africa. OBJECTIVE: This is a retrospective study on MBC in rural North Uganda, based on the pathology records of a private, non-profit, missionary hospital. METHODS: All male patients that had histological diagnosis of breast carcinoma from January 2009 to December 2016 were included in this study. RESULTS: In time span of 8 years, there were 337 consecutive breast cancer presentations, including 21 MBC (6.2%). The latter patients showed advanced disease (mean symptom duration: 20.3 months; mean tumour size: 5 cm) skin ulceration and ipsilateral lymph node metastasis: 60%). The mean age was 60.52 years (from 30 to 85 yrs). Ductal infiltrating carcinoma was the prevalent histological type in our series (65%), followed by an unusually high rate of papillary carcinomas (15%). There appeared to be a prevalence for left breasts (11 LT versus 6 RT; 64.7%), a finding also observed in the majority of MBC. CONCLUSIONS: This study is representative of the scenario in Northern Uganda, where MBC accounts for 6.2% of breast cancers, More information on the occurrence and risk factors of this unusual neoplasm in African countries may prompt prevention of chronic liver disease and early recognition and treatment of MBC.

PD-L1 expression is associated with tumor infiltrating lymphocytes that predict response to NACT in squamous cell cervical cancer.

Cancer immunotherapy has significantly improved the management of many malignancies in recent years. Although cervical cancer is the second most common women's cancer in the world, there are still few information about the role of checkpoint inhibitors in this neoplasm, especially in the neoadjuvant setting. In the present study, we retrieved 38 consecutive patients with squamous cell cervical cancer who underwent platinum-based neoadjuvant chemotherapy (NACT) followed by radical surgery. Pre-therapy biopsies were evaluated for the presence of tumor-infiltrating lymphocytes (TILs), including T (both cytotoxic CD8+ and helper CD4+) and B lymphocytes, macrophages, natural-killer cells, and eosinophils. Immunohistochemistry was performed to characterize the inflammatory cells and to evaluate programmed death-ligand 1 (PD-L1) expression on both neoplastic and inflammatory cells. We divided our study population in three groups using three cut-offs (< 10%, 10-40%, >40%), for both TILs and PD-L1 evaluation. Pathological response to NACT was obtained from the histological reports of the post-therapy surgical specimens. We observed that all cases showed stromal TILs, with a predominance of CD3+/CD4+ T helper cells, thus supporting the strong immunogenic potential of cervical cancer. The vast majority of neoplasms expressed PD-L1: 100% on immune cells and 92% on tumor cells. Firstly, we noticed that the percentage of neoplastic cells PD-L1+ was positively associated with high TIL percentage (p = 0.0073) and with increased PD-L1 expression on inflammatory cells (p = 0.0297). Secondly, we observed a significant correlation between both the percentage (p = 0.0105) of TILs and the expression of PD-L1 (p = 0.01045) on inflammatory cells and pathological response to NACT. These results suggest that cervical cancer could be a good target for immunotherapy, also in the neoadjuvant setting. Furthermore, PD-L1 expression was significantly associated with stromal TILs that interestingly may predict pathological response to NACT.

CTNNB1 p.L31P mutation in an ovarian endometrioid carcinoma with synchronous uterine endometrioid carcinoma.

We performed next generation sequencing of DNA extracted from the neoplastic tissues obtained from a patient who underwent surgery for a large right ovarian carcinoma (OC) of endometrioid type associated with endometrial cancer (EC). This was done in order to ascertain whether the tumors were synchronous endometrial/ovarian cancers or an advanced metastatic stage from either the ovary or the uterus. Pathologic criteria favoured synchronous EC/OC. We identified a PTEN c.959 T > G (p.L320X) truncating mutation occurring with similar allele frequency in both neoplastic tissues (ovary: 88 %, endometrium 89 %) and a CTNNB1 c.100C > G (p.S37C) activating mutation, with a comparable allelic frequency in both tumor tissues (ovary 51 %, endometrium 52 %). The shared genetic mutations, and the presence of PTEN c.959 T > G (p.L320X) truncating mutation, albeit at low allelic frequency (6 %), in the healthy peritumoral endometrial tissue, appear to confirm the recent literature on a primary endometrial origin for synchronous EC/OC. A third mutation was CTNNB1 c.92 T > C (p.L31 P), a missense mutation occurring with a low allele frequency (3.7 %) only in the ovarian cancer tissue. This mutation is only occasionally described in hepatocellular carcinomas.