molecular pathology of intraductal papillary mucinous neoplasms of the pancreas

Since the first description of intraductal papillary mucinous neoplasms(IPMNs)of the pancreas in the eighties,their identification has dramatically increased in the last decades,hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases.However,the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions.The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed.We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms,identifying some genes,molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy.The knowledge of molecular biology of IPMNs has impressively developed over the last few years.A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified,in pancreatic juice or in blood or in the samples from the pancreatic resections,but further researches are required to use these informations for clinical intent,in order to better define the natural history of these diseases and to improve their management.

European vs 2015-World Health Organization clinical molecular and pathological classification of myeloproliferative neoplasms

The BCR/ABL fusion gene or the Ph^1-chromosome in the t(9;22)(q34;q11)exerts a high tyrokinase acticity,which is the cause of chronic myeloid leukemia(CML).The1990 Hannover Bone Marrow Classification separated CML from the myeloproliferative disorders essential thrombocythemia(ET),polycythemia vera(PV)and chronic megakaryocytic granulocytic myeloproliferation(CMGM).The 2006-2008 European Clinical Molecular and Pathological(ECMP)criteria discovered 3variants of thrombocythemia:ET with features of PV(prodromal PV),"true"ET and ET associated with CMGM.The 2008 World Health Organization(WHO)-ECMP and 2014 WHO-CMP classifications defined three phenotypes of JAK2^(V617F)mutated ET:normocellular ET(WHO-ET),hypercelluar ET due to increased erythropoiesis(prodromal PV)and ET with hypercellular megakaryocytic-granulocytic myeloproliferation.The JAK2^(V617F)mutation load in heterozygous WHO-ET is low and associated with normal life expectance.The hetero/homozygous JAK2^(V617F)mutation load in PV and myelofibrosis is related to myeloproliferative neoplasm(MPN)disease burden in terms of symptomaticsplenomegaly,constitutional symptoms,bone marrow hypercellularity and myelofibrosis.JAK2 exon 12mutated MPN presents as idiopathic eryhrocythemia and early stage PV.According to 2014 WHO-CMP criteria JAK2 wild type MPL^(515)mutated ET is the second distinct thrombocythemia featured by clustered giant megakaryocytes with hyperlobulated stag-horn-like nuclei,in a normocellular bone marrow consistent with the diagnosis of"true"ET.JAK2/MPL wild type,calreticulin mutated hypercellular ET appears to be the third distinct thrombocythemia characterized by clustered larged immature dysmorphic megakaryocytes and bulky(bulbous)hyperchromatic nuclei consistent with CMGM or primary megakaryocytic granulocytic myeloproliferation.

Sarin Induced Lung Pathology and Protection by Standard Therapy Regime

The effects of atropine, diazepam and pralidoxime were studied for their ability to block the pathological lesions induced by sarin. Rats were exposed to an aerosol of sarin at a concentration of 51.2mg-m for 15 min following the pretreatment with one of the following combinations: atropine (10 mg/kg, i.m.) and diazepam (0.5 mg/kg, i.m.); atropine and pralidoxime (25 mg/kg, i.m.); diazepam and pralidoxime; atropine, diazepam and pralidoxime. Lung exposed to sarin aerosols revealed an increased cellular proliferation with progressive diffused interstitial thickening on the 4th day following exposure. On the 16th day, loss of alveolar space and consolidation of large areas of all lobes were observed. Sarin also caused damage to the respiratory bronchioles. All the therapy regime blocked the development of lung lesions in the descending orders: atropine, diazepam and pralidoxime, atropine and diazepam > diazepam and pralidoxime > atropine and pralidoxime. The result suggests that diazepam in combination with atropine and pralidoxime could be an effective drug combination regime for the lung lesions.

PVSG and WHO vs European Clinical,Molecular and Pathological Criteria for prefibrotic myeloproliferative neoplasms

The Polycythemia Vera Study Group(PVSG),World Health Organization(WHO) and European Clinical,Molecular and Pathological(ECMP) classifications agree upon the diagnostic criteria for polycythemia vera(PV) and advanced primary myelofibrosis(MF). Essential thrombocythemia(ET) according to PVSG and 2007/2008 WHO criteria comprises three variants of JAK2V617 F mutated ET when the ECMP criteria are applied. These include normocellular ET,hypercellular ET with features of early PV(prodromal PV),and hypercellular ET due to megakaryocytic,granulocytic myeloprolifera-tion(ET.MGM). Evolution of prodromal PV into overt PV is common. Development of MF is rare in normocellular ET(WHO-ET) but rather common in hypercellular ET.MGM. The JAK2V617 F mutation burden in heterozygous mutated normocellular ET and in heterozygous/homozygous or homozygous mutated PV and ET.MGM is of major prognostic significance. JAK2/MPL wild type ET associated with prefibrotic primary megakaryocytic and granulocytic myeloproliferation(PMGM) is characterized by densely clustered immature dysmorphic megakaryocytes with bulky(bulbous) hyperchromatic nuclei,which are never seen in JAK2V617 F mutated ET,and PV and also not in MPL515 mutated normocellular ET(WHO-ET). JAK2V617 mutation burden,spleen size,LDH,circulating CD34+ cells,and pre-treatment bone marrow histopathology are mandatory to stage the myeloproliferative neoplasms ET,PV,PMGM for proper prognosis assessment and therapeutic implications. MF itself is not a disease because reticulin fibrosis and reticulin/collagen fibrosis are secondary responses of activated polyclonal fibroblasts to cytokines released from the clonal myeloproliferative granulocytic and megakaryocytic progenitor cells in ET.MGM,PV and PMGM.

Parotid metastasis of rare lung adenocarcinoma:A case report

BACKGROUND Lung cancer(LC)is the leading cause of malignancy-related deaths worldwide.The most common sites of metastasis include the nervous system,bone,liver,respiratory system,and adrenal glands.LC metastasis in the parotid gland is very rare,and its diagnosis presents a challenge.Here,we report a case of parotid metastasis in primary LC.CASE SUMMARY The patient was a 74-year-old male who was discovered to have bilateral facial asymmetry inadvertently two years ago.The right earlobe was slightly swollen and without pain or numbness.Computed tomography(CT)examination showed bilateral lung space-occupying lesions.Pulmonary biopsy was performed and revealed adenocarcinoma(right-upper-lung nodule tissue).Positron emission tomography-CT examination showed:(1)Two hypermetabolic nodules in the right upper lobe of the lung,enlarged hy-permetabolic lymph nodes in the right hilar and mediastinum,and malignant space-occupying lesion in the right upper lobe of the lung and possible metastasis to the right hilar and mediastinal lymph nodes;and(2)multiple hypermetabolic nodules in bilateral parotid glands.Parotid puncture biopsy was performed considering lung adenocarcinoma metastasis.Gene detection of lung biopsy specimens revealed an EGFR gene 21 exon L858R mutation.CONCLUSION This case report highlights the challenging diagnosis of parotid metastasis in LC given its rare nature.Such lesions should be differentiated from primary tumors of the parotid gland.Simple radiological imaging is unreliable,and puncture biopsy is needed for final diagnosis of this condition.

Blastic plasmacytoid dendritic cell neoplasm in Jinhua,China:Two case reports

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,lymph nodes,and bone marrow,with rapid clinical progression and a poor prognosis.The BPDCN diagnosis is mainly based on the immunophenotype.CASE SUMMARY In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.CONCLUSION In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.

Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment:A Case report

BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung cancer(NSCLC).CASE SUMMARY A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment.Secondary pathological tissue biopsy confirmed squamous cell carcinoma(SCC)transformation.Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time,while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC.Notably,EGFR-TKIs resistance includes primary and acquired.Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs,with SCC transformation being relatively rare.Our results provide more detailed results of the patient’s diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma.CONCLUSION Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.

Relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma

Objective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:A total of 297 patients from July 2009 to May 2013 were chosen as objects.EGFR gene mutation were detected with fluorescence quantitative PCR.Relevance of EGFR gene mutation with clinical and pathological features was analyzed,and the prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was compared.Results:In 297 patients.136(45.79%) showed EGFR gene mutation.EGFR gene mutation had no significant relevance with age.gender,smoking history,family history of cancer and clinical stage(P>0.05);there was significant relevance between EGFR gene mutation and blood type,pathologic types,differentiation and diameter of cancer(P<0.05).The difference between prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was statistical significance(P<0.05).Conclusions:EGFR gene mutation has significant relevance with pathological features,the prognosis of EGFRmutant-paticnts is better than that of EGFR- wide type-patients.

Pathological features and diagnosis of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm(IPMN) of the pancreas is a noninvasive epithelial neoplasm of mucinproducing cells arising in the main duct(MD) and/or branch ducts(BD) of the pancreas.Involved ducts are dilated and filled with neoplastic papillae and mucus in variable intensity.IPMN lacks ovarian-type stroma,unlike mucinous cystic neoplasm,and is defined as a grossly visible entity(≥ 5 mm),unlike pancreatic intraepithelial neoplasm.With the use of high-resolution imaging techniques,very small IPMNs are increasingly being identified.Most IPMNs are solitary and located in the pancreatic head,although 20%-40% are multifocal.Macroscopic classification in MD type,BD type and mixed or combined type reflects biological differences with important prognostic and preoperative clinical management implications.Based on cytoarchitectural atypia,IPMN is classified into low-grade,intermediategrade and high-grade dysplasia.Based on histological features and mucin(MUC) immunophenotype,IPMNs are classified into gastric,intestinal,pancreatobiliary and oncocytic types.These different phenotypes can be observed together,with the IPMN classified according to the predominant type.Two pathways have been suggested:gastric phenotype corresponds to less aggressive uncommitted cells(MUC1-,MUC2-,MUC5 AC +,MUC6 +) with the capacity to evolve to intestinal phenotype(intestinal pathway)(MUC1-,MUC2 +,MUC5 AC +,MUC6- or weak +) or pancreatobiliary /oncocytic phenotypes(pyloropancreatic pathway)(MUC1 +,MUC 2-,MUC5 AC +,MUC 6 +) becoming more aggressive.Prognosis of IPMN is excellent but critically worsens when invasive carcinoma arises(about 40% of IPMNs),except in some cases of minimal invasion.The clinical challenge is to establish which IPMNs should be removed because of their higher risk of developing invasive cancer.Once resected,they must be extensively sampled or,much better,submitted in its entirety for microscopic study to completely rule out associated invasive carcinoma.

The Clinical Usefulness of ^(99m)Tc-Tetrofosmin Scintigraphy in the Diagnosis of Lung Neoplasmas and Mediastinal Lymphoid Node Involvement

In order to investigate the clinical significance of 99mTc-Tetrofosmin （TF） scintigraphy in the evaluation of lung cancer and mediastinal lymphoid node involvement, 33 patients with pulmo- nary neoplasmas were subjected to both 99mTc-TF scintigraphies and CT scans in one week before their operations or puncturations. All the images were judged visually and the emission images were analyzed with semi-quantitative methods in addition. The results of each group were compared. There was marked difference in target/non-target （T/N） ratio between the lung cancer group and the benign lesion group （P〈0.001）. Moreover, in the lung cancer group, T/N ratio in tomographies was signifi- cantly higher than that in planar images （P〈0.01）. The sensitivity and accuracy of semi-quantitative analysis in 99mTc-TF SPECT were significantly higher than those of CT in the diagnosis of pulmonary neoplasmas （P〈0.05 and P〈0.01 respectively）, so was the sensitivity of 99mTc-TF SPECT vs CT in the diagnosis of mediastinal lymphoid node metastasis （P〈0.05）. It was also found that epidermoid squamous cell carcinomas and adenocarcinomas had a higher T/N ratio than in small cell carcinomas （P〈0.05）, and 2 h washout rate （WR） of adenocarcinomas was higher than that of epidermoid squamous cell carcinomas （P〈0.05）. In conclusion, 99mTc-TF scintigraphy showed a favorable diag- nostic accuracy in appraising lung cancers and mediastinal lymph node metastases. Furthermore semi-quantitative technology can improve the accuracy, and is potential to offer some information about histological type of the cancer tissue. Therefore, 99mTc-TF scintigraphy will be a useful tool in the diagnosis and staging of lung cancer.

Intraductal papillary-mucinous neoplasia of the pancreas:Histopathology and molecular biology

Intraductal papillary-mucinous neoplasm(IPMN) of the pancreas is a clinically and morphologically distinctive precursor lesion of pancreatic cancer,characterized by gradual progression through a sequence of neoplastic changes.Based on the nature of the constituting neoplastic epithelium,degree of dysplasia and location within the pancreatic duct system,IPMNs are divided in several types which differ in their biological properties and clinical outcome.Molecular analysis and recent animal studies suggest that IPMNs develop in the context of a field-defect and reveal their possible relationship with other neoplastic precursor lesions of pancreatic cancer.

PROXIMAL BRONCHIAL INVASION OF LUNG CANCER: ACLINICOPATHOLOGICAL STUDY

Objective: To investigate the characteristics of proximal bronchial invasion of lung cancer for different types. Methods: Proximal bronchus of 151 operatively resected specimens of hilar type lung cancer were selected for cross-sectional pathological study. Forty-one specimens were obtained from total pulmonectomy, and 110 from pulmonary lobectomy. Results: Evidence showed that the direct invasion of tumor cells through the submucosal layer or multiple layers was the major form of lung cancer spread; 96.6% of the cancerous invasion occurred at the proximal bronchial wall less than 1.5 cm apart from the margin of the cancer. The extension of invasion was correlated with the histopathologic type of cancer, mode of invasion and TNM classification (pT, pN). Besides, the invasion in the bronchial wall by metastatic lymph nodes was also an important way for the cancer to spread. Conclusion: In order to achieve the radical removal of a tumor, it is imperative to keep a distance of 1.5 cm or more between the excision margin of the bronchus and the tumor, and to completely resect the hilar and mediastinal lymph nodes.

Clinicopathologic characteristics and therapeutic responses of Chinese patients with non-small cell lung cancer who harbor an anaplastic lymphoma kinase rearrangement

Introduction: The rearrangement of the anaplastic lymphoma kinase(ALK) gene accounts for approximately 1%–6% of lung adenocarcinoma cases and deines a molecular subgroup of tumors characterized by clinical sensitivity to ALK inhibitors such as crizotinib. This study aimed to identify the relationship between ALK rearrangement and the clinico?pathologic characteristics of non?small cell lung cancer(NSCLC) and to analyze the therapeutic responses of crizotinib and conventional chemotherapy to ALK rearrangement in NSCLC patients.Methods: A total of 487 lung cancer patients who underwent testing for ALK rearrangement in our department were included in this study. ALK rearrangement was examined by using fluorescence in situ hybridization(FISH) assay.Results: Among the 487 patients, 44(9.0%) were diagnosed with ALK rearrangement by using FISH assay. In 123 patients with adenocarcinoma who were non?smokers and of a young age(≤58 years old), the frequency of ALK rearrangement was 20.3%(25/123). Short overall survival(OS) was associated with non?adenocarcinoma tumor type(P = 0.006), poorly diferentiated tumors(P al growth factor rece= 0.001), advanced?stage tumors(P < 0.001), smoking history(P ptor(EGFR)(P = 0.008), and wild?type epidermrter time to cancer p= 0.008). Moreover, patients with poorly diferentiated and advanced?stage tumors had a shorogression compared with those with well diferentiated(P = 0.023) and early?stage tumors(P = 0.001), respectively.Conclusions: ALK?rearranged NSCLC tends to occur in younger individuals who are either non?smokers or light smokers with adenocarcinoma. Patients with ALK rearrangement might beneit from ALK inhibitor therapy.

Clinicopathological Profile of Lung Cancers at an Institute from South India—A Record Based Retrospective Cohort Study

Introduction: Apart from smoking as the known risk factor for lung cancer, recent developments implicate occupational exposure to carcinogens, indoor air pollution and dietary factors as other causative agents. In our study, we have analyzed the clinical and pathological profile of lung cancer patients treated at our center over a period of 8 years. Aim: To find the demographic and clinicopathological profile of lung cancer patients admitted to the oncology unit. Methods: This retrospective record based analysis includes a cohort of 1248 patients diagnosed with lung cancer, at a tertiary cancer care center in Bangalore, South India. This study includes data of patients admitted during the period 2010 to 2018, retrieved from the Hospital’s emergency medical records (EMR). Their demographic profile, clinical correlates, radiological profile and diagnostic details were studied. Benign tumours, malignant pleural disease and sarcomatoid tumors were excluded from this study. Results: Adenocarcinoma (AC) was detected among 70.4% of patients, Squamous cell carcinoma (SCC) among 15.3% and Small cell lung cancer (SCLC) among 14.3% of lung cancer admissions. Male to female ratio was 2.95:1. It was found that the median age of lung cancer patients was 61 years. >60% of lung cancer patients were from the 51 - 70 year age-group. Across the three types of cancers among the patients in Stage 3B to 4 strata, >35% received palliative chemotherapy and >20% received palliative chemotherapy + radiation. Conclusion: In our study, AC is the most common histological subtype (>70%) of lung cancer. The outcome of lung cancer patients can be considerably impacted by addressing risk factors through preventive measures implemented in the community.

A CLINICOPATHOLOGICAL STUDY OF MEDIASTINAL LYMPH NODE METASTASIS OF LUNG CANCER

Objective: To investigate pathologically the characteristics of lung cancer metastasis by mediastinal lymph node ways (N2). Methods: Of 398 lung cancer patients who underwent radical pulmonectomy and extensive lymph node dissection, 160 patients were diagnosed as with N2 metastasis, their 352 groups of mediastinal lymph nodes invaded were subject to the pathological study. Results: Evidences showed that the N2 metastasis of lung cancer was very active. It appears as single group or multi-group or jumping-form metastasis, rating 41.2%, 58.8% and 29.3% respectively. In addition, the extension of N2 metastasis was large, the most concentrated site was the 7th group lymph node (48.8%), then the 4th, 3rd and 5th group, rating 45.6%, 31.3% and 25.6% respectively. The occurrence of N2 metastasis was highly correlated with the site, size, histopathological type and the grade of differentiation of the cancer. An another feature of N2 metastasis was the invasion of metastasized lymph node into the bronchial wall, especially in adenocarcinoma. Conclusion: In order to achieve the radical removal of tumor, it is necessary to dissect the lymph nodes of the hilar and upper and lower mediastinum at the homolateral thoracic cavity actively and completely; beside, attention may be paid to the bronchial wall invasion caused by the lymph nodes metastasized.

Pathological diagnosis and immunohistochemical analysis of minute pulmonary meningothelial-like nodules:A case report

BACKGROUND Minute Pulmonary Meningothelial-like Nodules(MPMNs)are rare benign pulmonary nodules,which are more common in elderly women and have a higher detection rate in lung tissues of patients with lung malignant diseases.Its origin is not yet clear.At present,there are few reports on the diagnostic methods such as imaging and pathological manifestations of MPMNs.This article reports a 70-year-old female patient with pulmonary adenocarcinoma combined with MPMNs and reviews of the relevant literature.CASE SUMMARY A 70-year-old women was admitted to our institution with feeling sour in her back and occasional cough for more than 2 mo.Computerized electronic scanning scan and 3D reconstruction images in our institution showed there were multiple ground-glass nodules in both of her two lungs.The biggest one was in the apicoposterior segment of left upper lobe,about 2.5 mm×9 mm in size.We performed thoracoscopic resection of the left upper lung apicoposterior segment of the patient,and the final pathological report was minimally invasive adenocarcinoma.Re-examination of high resolution computed tomography 21 mo after surgery showed multiple ground-glass nodules in both lungs,and a new groundglass nodule was found in the superior segment of the right lower lobe.We took pathological biopsy of the right upper lung and right lower lung nodules for the patient under thoracoscopy.The histomorphology of the right lower lobe nodule showed multiple lesions in the lung tissue,and the small foci in the alveolar septum were distributed in mild form of the aggregation of short spindle cells.The immunohistochemistry showed that the lesion was epithelial membrane antigen(EMA)(+),somatostatin receptor 2a(SSTR2a)(+),S-100(-),chromogranin A(-),Syn(-),cytokeratin(-)and HMB-45(-).The final diagnosis was minimally invasive adenocarcinoma,accompanied by MPMNs.We recommend that patients continue to receive treatment after surgery and to do regular follow-up observations.CONCLUSION The imaging manifestations of MPMNs are atypical,histomorphology and immunohistochemistry can assist in its diagnosis.This article reviews the relevant literature of MPMNs immunohistochemistry and shows that MPMNs are positive for EMA,SSTR2a,and progesterone receptor.

Prognostic Clinico-Pathological Features of 99 Cases Advanced Non-Small Cell Lung Cancer—Egyptian National Cancer Institute

Background: Worldwide, lung cancer is the most commonly diagnosed cancer and causes more deaths than any other cancer. In Egypt;it accounts for 7% of male cancer & 3% in females. It is considered to be 3rd most common cancer in Egyptian males & 6th most common of both sexes. Materials and Methods: A total of 99 advanced non-small cell lung cancer patients who underwent first line platinum containing chemotherapy in our institute were included in this study. All clinical and pathological data were collected from patient’s files retrospectively between 2012-2014. Results: All 99 cases were diagnosed at late stage IIIB-IV (59 cases were IIIB).The median age was 54 years (range: 30 - 70) with 53% of cases are ≥ 54 years. 71% were males with male: female ratio of 2.4:1. All male patients were chronic smokers. The most frequent symptom was coughing (68%). Most of the patients had primary lung cancer in the right lung (77%). The most common histological subtype was squamous cell carcinoma (35.4%) with 54 cases present with PS-I, the remain was PS-II. All cases received platinum containing chemotherapy. The majority of cases experienced a progressive disease 60.6%. The median progression free survival (PFS) was 6 months & median overall survival (OS) was 18 months. We found that PS, disease stage, pathological subtypes and response to treatment statistically affect both median OS & PFS. Age affects only OS. Conclusions: Our analysis suggests that some of clinico-pathological factors & response to first line platinum containing regimens affect both OS & PFS of advanced NSCLC. This may be beneficial as prognostic markers and further studies were needed to aid in identification and treatment of these patients.

Pathological Lung Lesions of COVID-19 and Opioid Use Disorder: A Post-Mortem Lung and Toxicology Examination of 43 Decedents

The COVID-19 pandemic has continued from 2019 to current times, exacerbating existing epidemics since its beginning. Pathologic lung lesions in acute cases have consisted of hyaline membrane disease and microthrombi. More severe cases have pathologic lesions of alveolar and bronchiolar epithelial necrosis, lymphocytic interstitial infiltrate, and peribronchiolar and perivascular lymphocytic infiltrate. The opioid epidemic is one epidemic exacerbated by COVID-19. Those with opioid use disorder (OUD) are more likely to have compromised lung function, of which infection with the SARS-CoV-2 virus can worsen. The combined symptoms lead to an increased risk of overdose. In addition to anatomical risks, those with OUD require person-to-person contact to obtain opioids. This enhances the spread of COVID-19 and increases the risk of acquiring the disease. Pathological findings in those with chronic OUD can contain fluorescing talc powder with multinucleated giant cells and granulomas in the lung tissue. Twenty-one positive cases and twenty-two negative cases were collected from COVID-19 suspicious decedents in Marion County Coroner’s Office. Toxicology screens and COVID-19 RT-PCR tests were run on each of the 43 decedents. Microscopic evaluation was done by hematoxylin and eosin (H & E) and Masson’s Trichrome stains. The age range of those collected was 3 to 81 years. The ethnicities were 1 Asian, 8 African American, 1 Cuban, 3 Hispanic, 29 Caucasian, and 1 unknown. The male to female ratio was 3.8:1. The histological features found in this study were alveolar and bronchiolar epithelial necrosis, lymphocytic interstitial infiltrates, perivascular and peribronchiolar lymphocytic infiltrate, fibrosis, microthrombi, and hyaline membrane. Fluorescing talc was seen in 5 cases with granulomas and multinucleated giant cells. Toxicology reports showed 11 drug-related deaths, with cocaine, methamphetamine, alcohol, fentanyl, morphine, acetyl fentanyl, and sertraline as the causative agents.

Complete pathological response in locally advanced non-small-cell lung cancer patient: A case report

BACKGROUND Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer(NSCLC).We describe the case of a patient with locally advanced node-positive NSCLC(LA-NSCLC)treated in a phase II prospective protocol with chemotherapy,accelerated hypofractionated radiotherapy(AHRT)and surgery in the preimmunotherapy era.CASE SUMMARY A 69-year-old male,ex-smoker(20 PY),with a Karnofsky performance status of 90,was diagnosed with locally advanced squamous cell lung carcinoma.He was staged by total body computed tomography(CT)scanning,and integrated 18Ffluorodeoxyglucose positron emission tomography/CT scan[cT4 cN3 cM0,stage IIIC according to TNM(tumor-node-metastasis)8th edition]and received AHRT between chemotherapy cycles,in accordance with the study protocol(EudractCT registration 2008-006525-14).At the end of the study the patient underwent surgery,which was not part of the protocol,and showed a complete pathological response.CONCLUSION This case report confirms that AHRT can be used successfully to treat primary LA-NSCLC with bilateral mediastinal lymph node involvement.Our case is of particular interest because of the pathological response after AHRT and the lack of surgical complications.We hypothesize that this radiotherapeutic approach,with its proven efficacy,could be delivered as a short course reducing treatment costs,increasing patient compliance and reducing toxicity.We are currently investigating the possibility of combining hypofractionation,chemotherapy and immunotherapy for patients with LA-NSCLC.

SIGNIFICANCE OF ELECTRON MICROSCOPIC EXAMINATION IN THE DIAGNOSIS OF PULMONARY NEOPLASMS

The significance of electronic microscopc examination(EM) in the diagnosis of pulmonary neoplasms was evaIuated in 40 cases of Patients with different kinds of Pulmonary neoplasms.In 27 of the 40 cases,final diagnoses were made by light microscope(LM) examination,while in the remaining 13 cases,LM faded to reach definite diagnoses which were established with the help of EM.By analyzing our data,we conclude that in the following situations,EM helps meet in the diagnosis of pulmonary neoplasm:1.diagnosis of neuroendocrinal carcinomas of the lung;2.diagnosis of some rare pulmonary neoplasm;3.documentation of the histologic origins of the matastatic pulmonary neoplasms and 4.differentiation of malignant mesothelioma with pleural metastasis of Pulmonary adenocarcinoma.