Reduced expression of secretogranin VGF in laryngeal squamous cell carcinoma.

Laryngeal cancer accounts for one-third of all head and neck tumors, with squamous cell carcinoma (SCC) being the most predominant type, followed by neuroendocrine tumors. Chromogranins, are commonly used as biomarkers for neuroendocrine tumors, including laryngeal cancer. It has been reported that secretogranin VGF, a member of the chromogranin family, can be also used as a significant biomarker for neuroendocrine tumors. However, the expression and role of VGF in laryngeal carcinomas have not been previously investigated. Therefore, the present study aimed to determine the expression levels of VGF in laryngeal SCC (LSCC). The present study collected tumor tissues, as well as serum samples, from a cohort of 15 patients with LSCC. The results of reverse transcription-quantitative PCR, western blot analysis and immunofluorescence assays showed that the selective VGF precursor was downregulated in patients with LSCC. Notably, in tumor tissue, the immunoreactivity for VGF was found in vimentin-positive cells, probably corresponding to T lymphocytes. The current preliminary study suggested that the reduced expression levels of VGF observed in tumor tissue and at the systemic level could sustain LSCC phenotype. Overall, VGF could be a potential biomarker for detecting neoplastic lesions with a higher risk of tumor invasiveness, even in non-neuroendocrine tumors.

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.

Lymphadenopathies before and during the Pandemic COVID-19: Increasing Incidence of Metastases from Solid Tumors.

Since December 2019, the world has experienced a pandemic caused by SARS-CoV-2, a virus which spread throughout the world. Anti-COVID19 measures were applied to limit the spread of the infection, affecting normal clinical practice. In 2020, studies on the possible impact of the pandemic considering the screening programs for early diagnosis of cancer were conducted, resulting in a prediction of delayed diagnosis of cancer. We performed a retrospective monocentric study on patients who present with the onset of lymphadenomegalies evaluated at our Hematological Department from February 2019 to October 2021 and undergoing excisional lymph-node biopsy. Three periods were considered: pre-pandemic, first pandemic period and second pandemic period (Group A, B and C). We included 258 patients who underwent a surgical biopsy and received a histological diagnosis. Hematological evaluation of outpatients sent by the general practitioner and surgical biopsies did not decrease among the three groups, despite limitations placed during this pandemic as well as new diagnoses of hematological malignancies. However, the diagnosis of metastatic cancer significantly increased from 2019 (7.8%) to 2021 (22.1%) (p = 0.042). Our data supports the hypothesis that the pandemic affected the national screening programs of early cancer detection.

Solid-pseudopapillary tumor of the pancreas. An extrapancreatic loco-regional site and a review of the literature.

BACKGROUND: Solid pseudopapillary tumors (SPT) of the pancreas are rare, low malignancy and predominantly affect young women, but it may be locally aggressive. Pancreatic resection is the main treatment for SPTs. However, low malignancy SPT may give insidious extrapancreatic invasions. CASE REPORT: A 20-year-old woman was admitted with non-specific abdominal pain and diarrhea. A 9-cm SPT of the pancreas was discovered with extra-pancreatic invasion of the left adrenal gland and the spleen, in close contact with the body-tail of the pancreas, proximal portion of the jejunum, splenic flexure of the colon and the gastric fundus, with no signs of infiltration. For the young patient, a pancreas-preserving tumor excision was performed, with en-bloc resection of the spleen and adrenal gland, lymphadenectomy of the splenic vessels (13 lymph-nodes) and pre-pancreatic lymph node dissection, with no need for distal pancreatectomy. The duration of the surgery was 145 min, with no transfusion. The woman's postoperative course was complicated by a splenic lodge abscess treated via CT-guided percutaneous drainage, and a left pleural effusion treated medically, with a hospital stay of 16 days. Histology confirmed the diagnosis of a 9- cm low-grade SPT of the pancreas. In a close follow-up, the patient was asymptomatic 21 months later, with no tumor recurrence and good health. CONCLUSIONS: Low-grade SPT of the pancreas with extra-pancreatic invasion of loco-regional organs can be treated by a pancreas-preserving approach to avoid a pancreatectomy. Moreover, still few cases of extra-pancreatic SPT are reported in the literature and there is an urgent need for more relevant evidence. KEY WORDS: Extrapancreatic, Frantz's tumor, Pancreas preserving, Pancreas, Pancreatic neoplasm, Solid pseudopapillary tumor, Solid pancreatic tumor.

Pilot Investigation on p75ICD Expression in Laryngeal Squamous Cell Carcinoma.

We investigated the p75 Neurotrophin Receptor (p75NTR) expression and cleavage product p75NTR Intracellular Domain (p75ICD) as potential oncogenic and metastatic markers in human Laryngeal Squamous Cell Carcinoma (LSCC). p75NTR is highly expressed in Cancer Stem Cells (CSCs) of the laryngeal epithelia and it has been proposed as a marker for stemness, cell migration, and chemo-resistance in different squamous carcinomas. To investigate the clinical significance of p75NTR cleavage products in solid tumors, full-length and cleaved p75NTR expression was analyzed in laryngeal primary tumors from different-stage LSCC patients, diagnosed at the Policlinico Umberto I Hospital. Molecular and histological techniques were used to detect the expressions of p75NTR and p75ICD, and ATP Binding Cassette Subfamily G Member 2 (ABCG2), a CSC marker. We found regulated p75NTR cleavage during squamous epithelial tumor progression and tissue invasion. Our preliminary investigation suggests p75ICD expression and localization as possible features of tumorigenesis and metastaticity. Its co-localization with ABCG2 in squamous cells in the parenchyma invaded by the tumor formation allows us to hypothesize p75NTR and p75ICD roles in tumor invasion and CSC spreading in LSCC patients. These data might represent a starting point for a comprehensive analysis of p75NTR cleavage and of its clinical relevance as a potential molecular LSCC signature, possibly helping diagnosis, and improving prognosis and personalized therapy.

Classic KSHV/HHV-8-positive Primary Effusion Lymphoma (PEL): A Systematic Review and Meta-Analysis of Case Reports.

Primary effusion lymphoma (PEL) is a large B-cell lymphoma growing within body-cavities caused by the Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8 (KSHV/HHV-8). It is mainly reported in HIV-infected patients. The uncommon occurrence in the elderly supports a form paralleling classic Kaposi sarcoma (KS), i.e. classic PEL, whose characteristics are relatively underexplored. To better understand the diagnostic modalities and clinical-epidemiological features of classic PEL, articles reporting cases of PEL were identified through MEDLINE/EMBASE databases (January 1998-July 2020) and screened according to PRISMA guidelines to extract individual-level data. A comparison was also performed between classic PEL and classic KS to evaluate similarities and differences. We identified 105 subjects (median age 77 years; 86% males), mainly from Mediterranean countries (52%, first Italy) and Eastern Europe (7%). Common comorbidities were heart failure (32%), cirrhosis (16%), and malignancy (20%) including lymphoid neoplasms. Pleural cavity was the commonest site (67%). PEL diagnosis was based on cytomorphology (89%), evidence of KSHV/HHV-8 infection (94%), EBV co-infection (28%) and clonality of IGH (59%), IGK (14%), TRG (9%) alone or in multiple combinations. Compared to KS, age (P<.001), gender-ratio (P=.08) and mortality (P<.001) were significantly higher in PEL, whereas the frequency of PEL as a second primary was similar (P=.44). This is the first systematic review of classic PEL case reports highlighting heterogeneity and lack of a uniform multidisciplinary approach at diagnosis, in the absence of specific guidelines as it happens for rare cancers. It is conceivable that classic PEL is still underdiagnosed in Mediterranean countries wherein KSHV/HHV-8 is endemic.

Circulating CD137+ T Cells Correlate with Improved Response to Anti-PD1 Immunotherapy in Patients with Cancer.

PURPOSE: CD137 molecule is expressed by activated lymphocytes, and in patients with cancer identifies the tumor-reactive T cells. In solid tumors, high levels of circulating CD137+ T cells are associated with the clinical response and the disease-free status. Here, we examined the role of the CD137+ T cells in the improvement of patients' selection for immunotherapy treatment. EXPERIMENTAL DESIGN: Peripheral blood mononuclear cells derived from 109 patients with metastatic cancer (66 patients for the identification cohort and 43 for the validation cohort) were analyzed for the expression of CD3, CD4, CD8, CD137, and PD1 molecules before the beginning of anti-PD1 therapy. Twenty healthy donors were used as control. The soluble form of CD137 (sCD137) was also analyzed. The CD137+ T cell subsets and the sCD137 were correlated with the clinicopathologic characteristics. The distribution of CD137+ T cells was also examined in different tumor settings. RESULTS: The percentage of CD137+ T cells was higher in healthy donors and in those patients with a better clinical status (performance status = 0-1, n°metastasis≤2) and these high levels were ascribed to the CD8+CD137+ T cell population. The high frequency of CD137+ and CD8+CD137+ T cells resulted as a prognostic factor of overall survival (OS) and progression-free survival (PFS), respectively, and were confirmed in the validation cohort. High levels of CD3+CD137+PD1+ lymphocytes were associated with a low number of metastasis and longer survival. Instead, the high concentration of the immunosuppressive sCD137 in the serum is associated with a lower PFS and OS. In tumor bed, patients with a complete response showed a high percentage of CD137+ and CD8+ T cells. CONCLUSIONS: We propose the CD137+ T subset as an immune biomarker to define the wellness status of the immune system for successful anticancer immunotherapy.

Early histologic findings of pulmonary SARS-CoV-2 infection detected in a surgical specimen.

Despite the current pandemic season, reports on pathologic features of coronavirus disease 19 (Covid-19) are exceedingly rare at the present time. Here we describe the pathologic features of early lung involvement by Covid-19 in a surgical sample resected for carcinoma from a patient who developed SARS-CoV-2 infection soon after surgery. The main histologic findings observed were pneumocyte damage, alveolar hemorrhages with clustering of macrophages, prominent and diffuse neutrophilic margination within septal vessels, and interstitial inflammatory infiltrates, mainly represented by CD8+ T lymphocytes. These features are similar to those previously described in SARS-CoV-1 infection. Subtle histologic changes suggestive pulmonary involvement by Covid-19 may be accidentally encountered in routine pathology practice, especially when extensive sampling is performed for histology. These findings should be carefully interpreted in light of the clinical context of the patient and could prompt a pharyngeal swab PCR test to rule out the possibility of SARS-CoV-2 infection in asymptomatic patients.

Indeterminate thyroid nodules (TIR3A/TIR3B) according to the new Italian reporting system for thyroid cytology: A cytomorphological study.

OBJECTIVE: The Italian reporting system for thyroid cytology classifies indeterminate lesions as TIR3A (low risk) or TIR3B (high risk) and is meant to provide practical guidance rather than a detailed consideration of morphological features. We aimed to assess which cytological features have the most diagnostic value and whether they are effective in classifying nodules as either TIR3A or TIR3B and in predicting histological outcomes. METHODS: Thyroid fine-needle aspirates from 111 indeterminate nodules were reviewed blinded to clinical information, TIR3A/TIR3B classification, and histology in order to assess which cytological features (pooled into artefacts, smear background, architectural and nuclear atypia, and oncocytes) differentiate TIR3A from TIR3B, and benign from malignant histological outcomes. RESULTS: Of the cytological features examined, those specific for TIR3B included high cellularity, nuclear atypia, oncocyte predominance and transgressing vessels. Features specific for TIR3A included artefacts, low cellularity and oncocyte sparseness. Other features, such as microfollicules/trabeculae, were non-specific. Due to the different distributions of these features, three TIR3B subgroups were identifiable: follicular lesions with oncocytic changes, pure follicular lesions, and follicular lesions with nuclear atypia, whereas no subgroups were identifiable in TIR3A. Nuclear atypia was a significant indicator of malignancy, whereas oncocyte predominance was not a reliable predictor of malignancy. High cellularity and microfollicules/trabeculae were not indicative of any histological outcome. CONCLUSIONS: The majority of the assessed features were good predictors of histological outcomes. The TIR3A category included undefined nodules due to the absence of characterising features, whereas the TIR3B category included nodules with a greater number of distinguishing features.

Loss of BRCA1-associated protein 1 (BAP1) expression is useful in diagnostic cytopathology of malignant mesothelioma in effusions.

BACKGROUND: The important diagnostic challenge facing the cytopathologist is whether a mesothelial proliferation on effusions represents a malignant mesothelioma (MM) or a benign mesothelial hyperplasia (MH). Here, we evaluated the diagnostic utility of BAP1 immunohistochemistry (IHC) in distinguishing between reactive and neoplastic mesothelial cells. METHODS: In pleural and peritoneal effusions from 147 patients with diagnosed MM or with a differential diagnosis of MM and MH, the expression of BAP1 was examined by IHC on paraffin-embedded cell blocks (n = 121) and biopsies (n = 44). Included were also synchronous and methacronous cytology/biopsy pair samples. BAP1 IHC was evaluated for nuclear staining as positive or negative on target mesothelial cells, with appropriate internal control. RESULTS: In MM cases, loss of BAP1 nuclear staining was observed in 76.5% of the cell blocks and 47.5% of the biopsies. All BAP1-negative cases with a differential diagnosis of benign and malignant mesothelial proliferations were MM at follow-up. All MH cases, the 29% of epithelial MM and the 90% of nonepithelial MM, retained BAP1 expression. Synchronous and methacronous biopsy/cytology pairs showed matching BAP1 results. CONCLUSION: In effusions with mesotheliomatous cells or atypical mesothelial cells of uncertain significance, negative BAP1 IHC strongly supports a diagnosis of MM. With prudence in interpreting immunostaining, BAP1 may be included in IHC panels for MM cytodiagnosis, given its high specificity and sensitivity.