Cerebellar metastasis of ovarian cancer: a case report.

BACKGROUND: Ovarian cancer is metastatic at presentation in about 62% of cases, but brain metastases are rare, reported in 3.3-4% of patients. Brain metastasis seems to be more frequent in advanced stages at diagnosis and in patients with BRCA1/2 mutation. CASE PRESENTATION: We present a case of a 47-year-old Caucasian woman, BRCA wild type, with an ovarian cancer that started with single cerebellar metastasis. CONCLUSION: Brain metastases in ovarian cancer are rare and complex for diagnosis and management. This case focuses both on diagnosis and treatment, emphasizing the importance of a multimodal approach in a multidisciplinary team.

Metabolic Profile of Whole Unstimulated Saliva in Patients with Sjögren's Syndrome.

Primary Sjögren's Syndrome (pSS) is a multi-system autoimmune disease that involves the exocrine glands. Lymphocytes infiltrate the gland tissue, leading to anatomical modification and hypofunction. Even if the prognosis of pSS is favorable, quality of life is typically reduced due to the diverse manifestations of the disease. The aim of this study is to compare the salivary metabolomes of pSS with healthy controls (HCs). Seven cases were selected from a cohort of pSS patients, and six age- and sex-matched HCs were recruited from a cohort of volunteers. Whole unstimulated saliva was collected for NMR analysis. Our metabolomic analysis focused on 360 ms total echo 1D 1H NMR CPMG spectra. Metabolites detected with CPMG NMR spectra were assigned through 2D NMR spectra (COSY, TOCSY, and HSQC). About 50 metabolites were detected and assigned. Unsupervised exploratory PCA returned partial clustering, and PLS-DA improved the separation between pSS and HCs, highlighting a pool of metabolites distinctly describing each group. Despite the limited number of samples, the presented preliminary data are promising. PLS-DA indicated well-defined group separation, suggesting that the application of 1H-NMR metabolomics is suitable for the study of pSS.

Fulminant Sepsis and Perinatal Death at 23 Weeks Due to Fusobacterium nucleatum.

Introduction: Fusobacterium nucleatum is a gram-negative anaerobe, a constituent of the oral microflora, responsible for chronic periodontal diseases. Case Report: We describe a preterm infant with premature rupture of membranes at 23 weeks of gestational age due to F. nucleatum. The newborn died soon after birth. Placental histopathology showed severe necrotizing chorioamnionitis and funisitis with gram-negative bacilli. After autopsy, F. nucleatum was microbiologically isolated from the lung. The mother had dental hygiene 1 day before delivery, presenting mild and diffuse gingivitis. At admission, she had leukocytosis, foul-smelling vaginal discharge, but no fever. Conclusion: This case highlights the possibility of F. nucleatum spreading from oral cavity after a dental procedure to the placenta with chorioamnionitis and fetal infection. This raises the question of whether dental procedures during pregnancy should be accompanied by prophylactic antibiotics.

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment.

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-ß, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients' serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells.

Gastrointestinal Manifestations in Systemic Mastocytosis: The Need of a Multidisciplinary Approach.

Mastocytosis represents a heterogeneous group of neoplastic mast cell disorders. The basic classification into a skin-limited disease and a systemic form with multi-organ involvement remains valid. Systemic mastocytosis is a disease often hard to diagnose, characterized by different symptoms originating from either the release of mast cell mediators or organ damage due to mast cell infiltration. Gastrointestinal symptoms represent one of the major causes of morbidity, being present in 60-80% of patients. A high index of suspicion by clinicians and pathologists is required to reach the diagnosis. Gastrointestinal mastocytosis can be a challenging diagnosis, as symptoms simulate other more common gastrointestinal diseases. The endoscopic appearance is generally unremarkable or nonspecific and gastrointestinal mast cell infiltration can be focal and subtle, requiring an adequate sampling with multiple biopsies by the endoscopists. Special stains, such as CD117, tryptase, and CD25, should be performed in order not to miss the gastrointestinal mast cell infiltrate. A proper patient's workup requires a multidisciplinary approach including gastroenterologists, endoscopists, hematologists, oncologists, and pathologists. The aim of this review is to analyze the clinicopathological features of gastrointestinal involvement in systemic mastocytosis, focusing on the relevance of a multidisciplinary approach.

How Can We Treat Vulvar Carcinoma in Pregnancy? A Systematic Review of the Literature.

According to our systematic literature review (PRISMA guidelines), only 37 vulvar squamous cell carcinomas (VSCCs) were diagnosed during pregnancy (age range: 17-41 years). The tumor size range was 0.3-15 cm. The treatment was performed after (14/37, 38%), before (10/37, 27%), or before-and-after delivery (11/37, 30%). We found that 21/37 (57%) cases were stage I, 2 II (5%), 11 III (30%), and 3 IVB (8%). HPV-related features (condylomas/warts; HPV infection; high-grade squamous intraepithelial lesion) were reported in 11/37 (30%) cases. We also found that 9/37 (24%) patients had inflammatory conditions (lichen sclerosus/planus, psoriasis, chronic dermatitis). The time-to-recurrence/progression (12/37, 32%) ranged from 0 to 36 (mean 9) months. Eight women died of disease (22%) 2.5-48 months after diagnosis, 2 (5%) were alive with disease, and 23 (62%) were disease-free at the end of follow-up. Pregnant patients must be followed-up. Even if they are small, newly arising vulvar lesions should be biopsied, especially in women with risk factors (HPV, dermatosis, etc.). The treatment of VSCCs diagnosed in late third trimester might be delayed until postpartum. Elective cesarean section may prevent vulvar wound dehiscence. In the few reported cases, pregnancy/fetal outcomes seemed to not be affected by invasive treatments during pregnancy. However, clinicians must be careful; larger cohorts should define the best treatment. Definite guidelines are lacking, so a multidisciplinary approach and discussion with patients are mandatory.

Gynecological malignancy mimicking a thyroid lymph node metastasis.

SUMMARY: We present the case of a 69-year-old woman who attended the Endocrinology Unit of Modena for a suspicious lymph node in the left cervical compartment discovered during the follow-up of a recurrent gynecological malignancy. At neck ultrasonography, a thyroid goiter was detected, and the further cytological examination was inconclusive for thyroid nodule and compatible with a localization of an adenocarcinoma with papillary architecture for the lymph node. The histological examination after a left neck dissection confirmed the presence of an intracapsular metastasis of a papillary carcinoma immunohistochemically focally positive for thyroid transcription factor 1 and paired box 8 and negative for thyroglobulin. Subsequently, in the suspicion of a thyroid primitiveness, a total thyroidectomy was performed, revealing an intraparenchymal follicular variant of papillary thyroid carcinoma of 2 mm in the right lobe. During the follow-up, the appearance of a suspected cervical metastatic lesion led to another neck dissection, histologically compatible with a papillary carcinoma localization, immunohistochemically focally positive for thyroid transcription factor 1 and paired box 8, and negative for thyroglobulin. The histological revision of surgical specimens suggests the cervical recurrence of the prior gynecological cancer, rather than a thyroid carcinoma metastasis. The case described shows how carefully the cytological, histological and immunoistochemical results must be evaluated in oncological management, considering the whole patient's history. LEARNING POINTS: Neck lymph node metastases occasionally originate from anatomically distant primary sites, such as breast, lung, gastro-intestinal tract, genito-urinary tract and CNS. Histological and immunohistochemical evaluations play an important role to identify the primary malignant site, although in some cases they could mislead the clinicians. A multidisciplinary approach and the evaluation of the whole medical history of the patient are mandatory to guide the diagnostic-therapeutic path and to avoid unnecessary treatments.

Siblings with Acquired Tracheocele: Possible Hereditary Etiopathogenesis?

Tracheocele is a herniation of the tracheal mucosa through a defect in the tracheal wall. Familiar and/or genetical factors have never been taken into consideration in the etiopathogenesis of acquired tracheocele. Acquired tracheocele occurred in a brother and a sister from India. CT scan of the neck showed an air cyst next to the right tracheal wall. They underwent surgical excision through a transverse cervical incision. Histopathology of the lesion revealed a fibrous sac lined by a pseudostratified columnar respiratory epithelium in both patients. They had no recurrence of tracheocele at 12 months follow up. Genetic counseling did not evidence any significative associated abnormalities. No previous cases of familiar acquired tracheocele have been reported in the literature. Given the rarity of the lesion occurring in more than one member of a family, hereditary factors could be supposed as contributing factors in the etiopathogenesis of acquired tracheocele.

Appendix Tumor Microenvironment.

The pathological features of the appendix tumors fundamentally recall those of the more frequent colorectal neoplasms, although with a higher relative incidence of carcinoids, due to the abundant presence of enteroendocrine cells in the appendix wall. Moreover, different types of lymphomas, Hodgkin and non-Hodgkin, arising from the extra-nodal mucosal-associated lymphatic tissue, can be encountered. The appendix tumor microenvironment (TME) consists of a cellular component and of a noncellular component: the former includes the immunocompetent cells, while the latter represents the support stroma. Particularly in carcinoids, the immune cell reaction can be explicated by tumor-infiltrating lymphocytes, which, in some circumstances, may arrange around and inside the tumor in a brisk fashion influencing favorably the prognosis. This active reaction has to be distinguished from any preexisting inflammatory condition of the appendix and from superimposed tumor complications, such as infection or ischemia. In practice, we consider the appendix TME a complex framework with immunological, mechanic, and metabolic functions, all supported by a marked neo-lymphoangiogenesis.

Surrogate Molecular Classification of Invasive Breast Carcinoma: A Comparison Between Core Needle Biopsy and Surgical Excision, With and Without Neoadjuvant Therapy.

Surrogate molecular classification identifies different subtypes of invasive breast carcinoma on the basis of their immunohistochemical markers. The purpose of the study is to verify whether the immunohistochemical markers and surrogate molecular subtypes can be correctly assessed on the core needle biopsy (CNB) when compared with the corresponding surgical excision (SE), with or without neoadjuvant treatment (NAT). Cases with invasive carcinomas identified on both CNB and SE were retrospectively selected. With immunohistochemistry for estrogen receptors (ER), progesterone receptors (PgR), Ki67, human epidermal growth factor receptor 2 (Her2), and molecular analysis for Her2, surrogate molecular classification was determined in 4 and 5 groups, according to the 2013 St Gallen consensus. A total of 1067 cases was considered and complete data for surrogate molecular classification were available for 988 cases (655 without NAT, 333 with NAT). Without NAT, concordance was strong for ER and Her2, moderate for PgR, and weak for Ki67; concordance for surrogate molecular classification was moderate. After NAT, lower concordance rates were recorded, with significant reduction of PgR (P<0.001) and Ki67 (P<0.001). Without NAT, the surrogate molecular subtypes of breast carcinoma can be reliably assessed on CNB; Ki67 and/or PgR may be repeated on SE when values are close to cutoffs to avoid tumor subtype misclassification. After NAT, it seems advisable to repeat at least Ki67 and PgR.