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BACKGROUND: To the authors' knowledge, the impact of the coronavirus disease 2019 (COVID-19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported. METHODS: Data regarding the activity of each cytopathology laboratory during 4 weeks of COVID-19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine-needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta-analytical approach. RESULTS: Overall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%-98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conversely, the percentage of samples from the urinary tract, serous cavities, breast, lymph nodes, respiratory tract, salivary glands, central nervous system, gastrointestinal tract, pancreas, liver, and biliary tract increased (P < .05). An overall increase of 5.56% (95% CI, 3.77%-7.35%) in the malignancy rate in nongynecological samples during the COVID-19 pandemic was observed. When the suspicious category was included, the overall increase was 6.95% (95% CI, 4.63%-9.27%). CONCLUSIONS: The COVID-19 pandemic resulted in a drastic reduction in the total number of cytology specimens regardless of anatomic site or specimen type. The rate of malignancy increased, reflecting the prioritization of patients with cancer who were considered to be at high risk. Prospective monitoring of the effect of delays in access to health services during the lockdown period is warranted. ispartof: CANCER CYTOPATHOLOGY vol:128 issue:12 pages:885-894 ispartof: location:United States status: published

Background: The novel coronavirus disease 2019 (COVID-19) has rapidly spread worldwide since the outbreak in Wuhan, China, in 2019, becoming a major threat to public health. The most common symptoms are fever, dry cough, shortness of breath, but subjects with COVID-19 may also manifest gastrointestinal symptoms, and in a few cases an involvement of the gallbladder has been observed. Case report: Here we present a case of 50-year-old male with SARS-CoV-2 infection who had abdominal pain, vomiting and diarrhea without respiratory symptoms and was finally diagnosed as acute acalculous cholecystitis (AAC). Laparoscopic cholecystectomy was performed and found a gangrenous gallbladder; the real-time reverse transcription polymerase chain reaction SARS-CoV-2 nucleic acid assay of the bile was negative. We also made a review of the literature and try to understand the hypothetic role of SARS-CoV-2 in the pathogenesis of AAC. Conclusions: We highlighted that it is noteworthy to look at gastrointestinal symptoms in patients with SARS-CoV-2 infection and take into account AAC as a possible complication of COVID-19. Although more evidence is needed to better elucidate the role of the pathogenic mechanisms of the SARS-CoV-2 in AAC, it is conceivable that the hepatobiliary system could be a potential target of SARS-CoV-2.

Background: In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 “lockdown” period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020). Methods: Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. Results: A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P

Summary The 2019 WHO classification of digestive system tumors significantly reformed the classificatory definition of serrated lesions of the colorectal mucosa and added new essential diagnostic criteria for both conventional adenomas and hereditary gastrointestinal polyposis syndromes. Histopathological examination of colorectal adenocarcinoma precursors lesions represents an important segment of daily clinical practice in a pathology department and is essential for the implementation of current colorectal adenocarcinoma secondary prevention strategies. This overview will focus on a schematic histopathological and molecular classification of precursor lesions arising within colorectal mucosa.

Summary Pancreatic malignant exocrine tumors represent the most important cause of cancer-related death for pancreatic neoplasms. The most common tumor type in this category is represented by pancreatic ductal adenocarcinoma (PDAC), an ill defined, stroma-rich, scirrhous neoplasm with glandular differentiation. Here we present the relevant characteristics of the most important PDAC variants, namely adenosquamous carcinoma, colloid carcinoma, undifferentiated carcinoma, undifferentiated carcinoma with osteoclast-like giant cells, signet ring carcinoma, medullary carcinoma and hepatoid carcinoma. The other categories of malignant exocrine tumors, characterized by fleshy, stroma-poor, circumscribed neoplasms, include acinar cell carcinoma (pure and mixed), pancreatoblastoma, and solid pseudopapillary neoplasms. The most important macroscopic, histologic, immunohistochemical and molecular hallmarks of all these tumors, highlighting their key diagnostic/pathological features are presented. Lastly, standardized indications regarding gross sampling and how to compile a formal pathology report for pancreatic malignant exocrine tumors will be provided.

A case of lymphoepithelioma-like (LEL) hepatobiliary carcinoma is reported. To date, only 89 cases of this rare neoplasm have been reported, with both hepatocellular and cholangiocellular histotype. The case reported here could be classified as LEL mixed hepatobiliary carcinoma (Hepato-Cholangio), a histotype not reported so far in the LEL variant.

The classification of flat non-neoplastic urothelial lesions has been evolved through the years in the attempt to better define a spectrum of morphologic entities with somewhat overlapping features. Differentiating these lesions is important because of differences in patient management and clinical outcome. Materials and methods and objective: A systematic review of the literature has been carried out in order to (1) assess the most striking clinical features of each lesion and (2) identify those morphological traits and immunophenotypical markers which may aid in the differential diagnosis.Our results point out the importance of a proper definition of flat non-neoplastic urothelial lesions in order to predict clinical behaviour and allow tailored patient management; therefore, we attempted to construct a novel and "easy to use" algorithm for a clear, standardized and evidence-based pathological diagnosis.

Chordomas are rare malignant tumors of notochordal origin and are rare locally aggressive ones with a metastatic potential. The skin rarely is seen as metastatic site. We describe a case of an adult woman with cutaneous metastasis of a primary sacral chordoma excised ten years before, which appeared as a painless cutaneous mass located in the dorsal region. Once removed, the surgical specimen was formalin fixed and in paraffin embedded. Sections were stained with haematoxylin-eosin, and histochemical and immunohistochemical investigations were performed. Histologically, the neoplasia was characterized by cords or single tumor cells with an abundant myxoid stroma, conspicuous pale vacuolated cytoplasm (the classic “physaliphorous cells”), and mild nuclear atypia. Mitotic activity was scanty. At immunohistochemistry, the tumor cells were diffusely positive for S-100 protein, pan-keratins, EMA, and vimentin. A diagnosis of cutaneous metastasis of chordoma was performed. This case illustrates a diagnostic challenge because of the unusual presentation of an already rare tumor.

Cutaneous Angiosarcoma of the elderly's face is a rare and peculiar neoplasm with all its own clinical and morphological characteristics. The observation of a classic case in the clinical presentation and morphology has offered the opportunity to revisit this topic.

The new WHO 2016 classification of renal neoplasia encounters the new entity called “clear cell papillary renal cell carcinoma” (ccpRCC). The ccpRCC has been long included as a subtype of clear cell RCC histotype and it actually ranges from 2 to 9% in different routinely available cohort of renal carcinomas. Of important note, ccpRCC does not show any recurrences or metastases or lymph-node invasion and the outcome is always good. We reviewed twenty-four publications with available follow-up for patients (no. 362) affected by clear cell papillary RCCs/renal adenomatoid tumours and notably ccpRCC harbors an indolent clinical behavior after a mean of 38 months (3,5 years) of follow-up. This paper reviews the histological, molecular and clinical features characterizing ccpRCC, with the goal of focusing the knowledge of the benign fashion of this new tumour entity, supporting the idea of a new renal cell adenoma recruited morphologically from ex conventional clear cell RCC tumours.

Cdk9 is a member of the Cdc2-like family of kinases. Its cyclin partners are members of the family of cyclin T (T1, T2a and T2b) and cyclin K. The Cdk9/Cyclin T complex appears to be involved in regulating several physiological processes. Recently, Cdk9 has been identified as a regulator of the differentiation program of several cell types, such as muscle cells, monocytes and lymphocytes, suggesting that it may have a function in controlling specific differentiative pathways. We analyzed whether Cdk9 and Cyclin T1 may be involved in the regulation of neuron and astrocyte differentiation. Cdk9 and Cyclin T1 expression levels were monitored during the differentiation program of neuroblastoma and astrocytoma cell lines. Our results suggest that Cdk9/Cyclin T1 complex may be required for neuron differentiation induced by retinoic acid, because the expression level of the complex varies during differentiation, but no significant changes were observed in its expression in the astrocytoma cell line. In addition, the expression of Cdk9 and Cyclin T1 was evaluated by immunohistochemistry in samples of neuroblastoma, PNET (Primary Neuroectodermal Tumor) and astrocytoma tumors of different grades, in order to assess whether there was a correlation between Cdk9 expression and tumor grading. Our results show that in neuroblastoma and PNET tumor samples Cdk9 is more expressed the more differentiated the tumor is. Conversely, no significant alteration of Cdk9 expression was observed in astrocytoma tumor samples of different grades, thus confirming the results obtained for the cell lines.

Aims Grafts have been shown to be sites where the alloimmune response develops in a direct interaction between the targeted tissue and the immune effectors. An important issue in renal rejection is B cell infiltrate that may contribute to the development or persistence of rejection. Analysis of gene-expression patterns also provides a window on the biology and pathogenesis of renal allograft rejection. Methods To better understand the role exerted by B cells in a renal acute rejection, the authors analysed the IgVH gene repertoire in six cases of transplanted kidneys with acute T cell-mediated rejection (TCMR), three of which were associated with antibody-mediated rejection (ABMR). Results The authors found mutated and unmutated sequences, without any evidence of clonal relationships, in all patients with TCMR alone and in two of the three cases with both acute TCMR and ABMR. The remaining patient showed glomerular inflammation and thrombosis, with diffuse C4d glomerular and peritubular capillary deposition, and hypermutated V region genes. Conclusions These results suggest that there is more than one pathway to the onset and perpetuation of CD20 (+) B cells infiltration in acute rejection; furthermore, the CD20 (+) B cells9 clonal expansion may be responsible for a more severe pattern of ABMR, through immune-mediated tissue damage.

We report 3 cases of lymphoid neoplasms with mixed lineage features of T-, NK-, or B-cell marker expression and clonal gene rearrangement for both T-cell receptor and immunoglobulin light chain IgK. A characteristic of our cases was the lack of expression of the specific B-cell transcription factor, Pax5, which is essential for maintaining the identity and function of mature B cells during late B lymphopoiesis. In the absence of Pax5, B cells in vitro can differentiate into macrophages, dendritic cells, granulocytes, and T/NK cells. Methylation analysis of the Pax5 gene in our cases suggests that its inactivation by this epigenetic event in a committed or mature B cell, before plasma cell differentiation, may well be a common pathogenetic mechanism in mature lymphoid neoplasms with expression of multilineage antigens. In particular, case 1 may represent a mixed NK- and B-cell lineage; and cases 2 and 3 may represent mixed T and B-cell lineage, respectively. Aberrations in the DNA methylation patterns are currently recognized as a hallmark of human cancer. Cases with aberrant phenotypes require molecular analysis for lineage assignment. Studies of such cases may be helpful to better elucidate whether they represent a distinct entity with clinical, immunophenotypic, and molecular characteristics or an incidental phenomenon during malignant transformation. Interestingly, these cases were all characterized by poor clinical outcome.

We describe the case of a 61-year-old patient with refractory splenic marginal zone lymphoma and secondary autoimmune hemolytic anemia, both successfully treated with rituximab. This case demonstrates that rituximab monotherapy might also be a valid therapeutic approach in marginal zone lymphoma and autoimmune hemolytic anemia after failure of first-line treatment. Maintenance therapy, although expensive, could be useful to improve event-free survival in patients with unfavorable clinical behavior.

We present two cases of small B-cell lymphomas of particular diagnostic interest because the histological patterns were at variance with their immunophenotype. One of these lymphomas, involving the gallbladder and duodenum, showed a marginal zone lymphoma-like (MALT type) pattern of cellular infiltration with CD5 negativity but (unexpectedly) Cyclin D1 positivity. Fluorescence in situ hybridization analysis of this case was performed because of the aberrant expression of Cyclin D1, and was clearly positive for the Cyclin D1 gene translocation. The second case, occurring in a lymph node, showed the typical growth pattern of a follicular lymphoma but it had an atypical immunophenotype, namely, expression of Cyclin D1, CD10, and Bcl2 and focally Bcl6, accompanied by a lack of CD5 and CD23. The Cyclin D1 gene translocation was detected by fluorescence in situ hybridisation (FISH), whereas c-myc and Bcl2 genes translocation were absent. Numerical chromosomal changes, which were visualized for chromosomes 8, 11, and 18 could be correlated to the aberrant immunoprofile. In this context, we discuss the diagnostic value of Cyclin D1, CD5, CD23, CD10, Bcl6 markers revealed by immunohistochemistry, as well as the significance of detection by FISH of chromosomal translocations such as t(11;14) and t(14;18). The question still remains as to whether such cases should be designated as specific lymphoma entities or reported as unclassifiable and the chromosome aberration reported.

We set out to analyze the presence of Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) in different neoplasms occurring in East Africa, a region characterized by a high KSHV/HHV-8 seroprevalence rate and endemic Kaposi's sarcoma (KS). Our results suggest that, in endemic regions of Africa, KSHV/HHV-8 is predominantly associated with KS, independently of HIV status. During the course of this study, other important information came to light. We found the presence of KSHV/HHV-8 in 2 cases of lymph nodes partially involved by Burkitt's lymphoma and KS and in 1 case of multicentric Castleman disease. Our immunophenotypic and molecular data seem to suggest 2 different mechanisms of viral infection are at work in lymphoid cells. On one hand, when B cells show a latent phase infection with KSHV/HHV-8, after the germinal center reaction, naive B cells become resting memory B cells, similarly to Epstein-Barr virus-infected B cells. On the other hand, when lytic genes such as vIL6 are expressed in naive B cells, they may be driven to differentiate into plasmablasts without undergoing germinal center reaction. Interestingly, among KSHV/HHV-8-positive cases, in those in which there was also lymphoma, the neoplastic cells were negative for KSHV/HHV-8. This further confirms that KSHV/HHV-8 is involved in the neoplastic transformation of only certain types of lymphoma, probably in relation to their precursor infected cell. In conclusion, the maturation stage of KSHV/HHV-8-positive B cells as well as the type of viral infection may well determine the morphological, phenotypic, and clinical characteristics of KSHV/HHV-8-associated lymphomas.