An 81-year-old man was evaluated in our hospital for upper abdominal pain and dyspepsia. At the time of his presentation, hematological examinations were within the normal limits, except for C-reactive protein (5.18 mg/dL) and hemoglobin (92.00 g/L). There was no alteration in liver function tests. Gastro-duodenoscopy was within normal limits. He underwent abdominal ultrasound (Fig. 1a) and contrast-enhanced multi-detector computed tomography (Fig. 1b), which revealed a heterogeneous hypo-echoic and hypo-dense sub-Glisson's capsule hepatic multiple nodular formations (range diameter from 0.9 to 3.1 cm) and the presence of hepatic hilar lymph nodes. The patient then performed serological and tumor markers; both types of tests resulted negative. After multidisciplinary discussion, the patient underwent ultrasound guided liver core needle biopsy. Hepatic histopathological evaluation demonstrated a malignant mesothelioma, consisting in predominantly epithelioid poorly differentiated as tumor cells or also known as ‘primary intrahepatic mesothelioma’ (Fig. 2). Given the intrahepatic multi-nodular form of malignant mesothelioma in our patient, he undergone to chemotherapy. Primary intrahepatic mesotheliomas are exceedingly rare tumors, and their incidence is not well defined. Clinical manifestation is present only in advanced forms and has non‑specific signs; this makes them difficult to diagnose. Intrahepatic malignant mesotheliomas develop from mesothelial cell layers covering Glisson's capsula and subsequently invades the hepatic parenchyma. Initial evaluation includes tumor markers for possible differential diagnosis of primary and secondary liver neoplasms. Consequently, imaging studies (ultrasound, multi-detector computed tomography, or magnetic resonance imaging) are to be performed as they allow us to evaluate the morphological characteristics and the intrahepatic and extrahepatic extension of the pathology. Generally, primary intrahepatic mesothelioma appears as a solitary tumor mass that is localized into the liver parenchyma. To our knowledge, an initial presentation of primary intrahepatic mesotheliomas with sub-Glisson's capsule hepatic multiple nodular formations, as in our patient, has not been described previously in the literature. Biopsy is mandatory to establish the correct nature diagnosis. Surgery is indicated in single hepatic nodule, all other case are treated by chemotherapy.
This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment.
Case 1: A case of left hydronephrosis referred four years after a right radical mastectomy for lobular breast carcinoma was described. Computed tomography scan revealed a left hydronephrosis with dilated ureter up to the proximal third. An exploratory laparoscopy was performed and the definitive histopathology examination showed a recurrence of the carcinoma with a right tubal metastasis and peritoneal carcinosis.
Case 2: A rare case of an extensive penile squamous cell carcinoma in a young man. The patient was treated with radical surgery and modified inguinal lymphadenectomy. No recurrence was noticed so far.
Case 3: A rare case of left sided Inferior Vena Cava (IVC) in a patient diagnosed with renal cell cancer who underwent open left partial nephrectomy.
Case 4: A case of urethrorrhagia, caused by a recent trauma from an urinary catheter placed in a patient submitted to gastric resection due to a neoplastic pathology. Urethrorrhagia only temporarily responded to conservative treatment and ultimately resolved by coagulation with an endoscopic approach.
The incidence of certain forms of tumors has increased progressively in recent years and is expected to continue growing as life expectancy continues to increase. Tumor-infiltrating NK cells may contribute to develop an anti-tumor response. Optimized combinations of different cancer therapies,, including NK cell-based approaches for targeting tumor cells, have the potential to open new avenues in cancer immunotherapy. Functional inhibitory receptors on NK cells are needed to prevent their attack on healthy cells. Nevertheless disruption of inhibitory receptors function on NK cells increases the cytotoxic capacity of NK cells against cancer cells. MicroRNAs (miRNAs) are small non-coding RNA molecules that target mRNA and thus regulate the expression of genes involved in the development, maturation, and effector functions of NK cells. Therapeutic strategies that target the regulatory effects of miRNAs have the potential to improve the efficiency of cancer immunotherapy. Interestingly, emerging evidence points out that some miRNAs can, directly and indirectly, control the surface expression of immune checkpoints on NK cells or that of their ligands on tumor cells. This suggests a possible use of miRNAs in the context of anti-tumor therapy. This review provides the current overview of the connections between miRNAs and regulation of NK cell functions and discusses the potential of these miRNAs as innovative biomarkers/targets for cancer immunotherapy.
Although endometrial cancer (EC) is a hormone dependent neoplasm, there are no recommendations for the determination of steroid hormone receptors in the tumor tissue and no hormone therapy has ever been assessed in the adjuvant setting. The purpose of this study was to explore the effect of adjuvant aromatase inhibitors (AIs) on progression-free survival (PFS) and overall survival (OS) in patients with early stage and steroid receptors-positive EC.We retrospectively analyzed clinical and pathological factors in 73 patients with high-risk (49.3%) or low-risk (50.7%) stage I (n = 71) or II (n = 2) endometrial cancer who received by their preference after counseling either no treatment (reference group) or AI. Prognostic factors were well balanced between groups. Expression of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67 index was correlated with clinical outcomes.Univariate and multivariate Cox proportional regression analyses, adjusted for age, grade, stage, depth of myometrial invasion, lymphovascular space invasion, BMI, ER, PgR and Ki-67 labeling index levels, showed that PFS and OS had a trend to be longer in patients receiving AI than in the reference group HR= 0.23 (95% CI; 0.04-1.27) for PFS and HR= 0.11 (95% CI; 0.01-1.36) for OS.Compared with no treatment, AI exhibited a trend toward a benefit on PFS and OS in patients with early stage hormone receptor-positive EC. Given the exploratory nature of our study, randomized clinical trials for ER/PgR positive EC patients are warranted to assess the clinical benefit of AI and the potential predictive role of steroid receptors and Ki-67.
Mature cystic teratomas (MCTs) (commonly called 'dermoid cysts') are cystic tumors composed of well-differentiated tissue derived from at least two of the three germ cell layers (ectoderm, mesoderm and endoderm). They usually arise in the ovaries but can be extragonadal, with uterine location exceedingly rare. We describe the sonographic features of an MCT presenting as an endometrial polyp in a 58-year-old asymptomatic woman, referred to our division after a 15-mm polyp was found following routine transvaginal ultrasound examination. Imaging was performed using a Siemens Aldara machine (Germany) with a 7.5-MHz convex transducer (Figure 1). The polyp was excised hysteroscopically and had a fibrous consistency, appearing as a 3 × 1-cm benign mucosal polyp with a smooth surface. Final pathology confirmed the diagnosis of MCT (Figure 2). Transvaginal ultrasound image, showing that the uterus has normal echogenicity and morphology with a homogeneously thin endometrium (thin arrow) and a hyperechoic endocavitary lesion of 15 mm (thick arrow). The image is suggestive of an endometrial polyp. Histological cross-section showing the inner wall of the cyst lined with mature squamous epithelium. Hair follicles, skin glands, adipocytes, cartilage and vascular structures are also present. All the elements are eutypic and mature, fitting the description of a mature cystic teratoma deriving from two germ cell layers. Clinical presentation of uterine MCTs includes abnormal uterine bleeding, cervical polyps, pelvic pain, vaginal discharge and enlargement of the uterus. In none of the cases reported in the literature was a clinical, preoperative diagnosis possible and in most cases the tumors were misdiagnosed as mucous cervical polyps. None of the patients underwent preoperative imaging studies. Most ovarian MCTs are diagnosed on ultrasound examination. Common sonographic features are a cystic lesion with a densely echogenic tubercle (Rokitansky nodule) projecting into the cystic lumen, and a diffusely or partially echogenic mass with sound attenuation because of hair and sebaceous material within the cyst and the presence of multiple thin, echogenic bands caused by the hairs in the cavity1-3. None of these features presented in this case of uterine MCT. Sonographic features depend on the content of the cyst and many unusual sonographic presentations have been described3-5. In this case, despite the presence of hair follicles and sebaceous glands, the lack of hairs, sebum and of the Rokitansky nodule explains the lack of typical sonographic features. Furthermore the good sensitivity and specificity of ultrasound examination in diagnosing ovarian MCTs are linked to the high prevalence of this lesion in the gonads and cannot be reproduced for extragonadal teratomas. It has been hypothesized that uterine teratomas originate either from pluripotent embryonic cells (e.g. residual tissues remaining in the uterus after a missed miscarriage or an undelivered papyraceous twin) owing to the genital canal being the natural pathway for the fertilized ovum (blastomere theory)6, 7, or from primordial cells that have gone astray during embryogenesis (parthenogenic theory), with extragonadal teratomas arising in sites to which germ cells normally migrate in early embryonic life8. Proliferating cells in benign cystic teratomas are derived from oocytes that have completed meiotic division and teratomas have a normal 46,XX karyotype, with identical X chromosomes derived solely from the host, making the parthenogenic theory more likely9. This case occurred in a postmenopausal woman with an obstetric history of two full-term pregnancies, who reported yearly gynecological check-ups with unremarkable routine transvaginal ultrasound examinations, further supporting the parthenogenic theory of MCTs. MCT should be included in the differential diagnosis of intracavitary uterine lesions even in the absence of typical features. A. Papadia*, M. Rutigliani , D. Gerbaldo*, E. Fulcheri , N. Ragni*, * Department of Obstetrics and Gynecology, San Martino Hospital, University of Genova, L.go R Benzi Pad 1, Genova, Italy 16132, Department of Pathology, San Martino Hospital, University of Genova, L.go R Benzi Pad 1, Genova, Italy 16132
D2-40 is a novel monoclonal antibody that recognizes a 40,000 Da O-linked sialoglycoprotein podoplanin. Although its use is becoming more common, little work has been done with human foetuses. We initiated an evaluation of D2-40 antibody immunoreactivity in developing cutaneous adnexa of human fetuses at various gestational ages. Starting from a retrospective cohort of 1,098 human fetal autopsies we identified and selected a total of 48 fetuses ranging from the 12th week gestational age to term appropriate for this study. We demonstrated that the gems of the hair follicles were D2-40 negative in fetuses from the 12th to 15th week gestation, positive in fetuses between the 16th and 20th week of gestation, negative in fetuses from the 21st week gestation to term. Normal adult controls were also negative. This is the first report to demonstrate intense D2-40 immunoreactivity in the gems of hair follicles of developing human skin.
We report a case of inflammatory colitis after SARS-CoV-2 infection in a patient with no additional co-morbidity who died within three weeks of hospitalization. As it is becoming increasingly clear that SARS-CoV-2 infection can cause immunological alterations, we investigated the expression of the inhibitory checkpoint PD-1 and its ligand PD-L1 to explore the potential role of this axis in the break of self-tolerance. The presence of the SARS-CoV-2 virus in colon tissue was demonstrated by qRT-PCR and immunohistochemical localization of the nucleocapsid protein. Expression of lymphocyte markers, PD-1, and PD-L1 in colon tissue was investigated by IHC. SARS-CoV-2-immunoreactive cells were detected both in the ulcerated and non-ulcerated mucosal areas. Compared to healthy tissue, where PD-1 is weakly expressed and PD-L1 is absent, PD-1 and PD-L1 expression appears in the inflamed mucosal tissue, as expected, but was mainly confined to non-ulcerative areas. At the same time, these markers were virtually undetectable in areas of mucosal ulceration. Our data show an alteration of the PD-1/PD-L1 axis and suggest a link between SARS-CoV-2 infection and an aberrant autoinflammatory response due to concomitant breakdown of the PD-1/PD-L1 interaction leading to early death of the patient.
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