Clinicopathological Diagnosis Research Articles

Parathyroid carcinoma with sarcomatoid differentiation: a case report and literature review

BackgroundParathyroid carcinoma (PC) is a rare thyroid tumor. PC with sarcomatoid differentiation(PCSD) is even rarer and its exact etiology remains unclear. We here report a case of PCSD, and present the clinicopathological features and pathological diagnosis and review the literature.Case presentationA 71-year-old man presented with a mass of 4.5 cm × 3.5 cm in the right neck. The tumor was composed of nest-like transparent cells, and the septum had heterotypic rhabdoid cells with sarcomatoid differentiation. Immunophenotype was as follows: myogenic differentiation 1(MyoD1), myogenin and desmin were positive; clear cells were positive for chromogranin A(CGA), synaptophysin(Syn) and GATA-3; and Ki-67 proliferation index was 40%. Hematoxylin and eosin staining and immunohistochemistry were performed. The patient was diagnosed with PCSD, and died 6 months after surgery.ConclusionsPCSD is a rare type of primary parathyroid tumor with high malignancy and poor prognosis. Definitive diagnosis should be based on histopathological morphology and immunophenotype, and surgical treatment should be performed as soon as possible.

Clinicopathological features of polymorphous low-grade neuroepithelial tumor of the young

Objective: To investigate the clinicopathological features, diagnosis and prognosis of polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Methods: Two cases of PLNTY diagnosed during January 2016 to December 2019 were collected from Ningbo Diagnostic Pathology Center, Zhejiang, China. The clinical features, histopathological characteristics, immunohistochemical and molecular genetic findings were analyzed and the relevant literature was reviewed. Results: The two patients were both female, at the ages of 14 and 25 years, respectively. Both patients presented with seizure attacks. The imaging study showed a mixed signal in the cerebral cortex, located in the occipital and temporal lobes, respectively. Microscopically, the tumors were characterized by the invariable presence of oligodendroglioma-like appearance, often with calcification. Immunohistochemically, the tumors were diffusely and intensely CD34 positive with ramified, CD34-expressing neural elements in regional cortex. The tumors were positive for GFAP, Olig2 and ATRX, and negative for IDH1, Neu N, nestin and EMA. The Ki-67 labeling index was less than 2%. The case number 2 harbored the BRAF V600E mutation, while the case number 1 was negative for both the BRAF V600E mutation and 1p/19q codeletion. Both patients recovered very well and were free of seizures after the following-up of 2 and 24 months, respectively. Conclusions: PLNTY is an uncommon neuroepithelial tumor. Histopathologic and immunohistochemical examinations are necessary for establishing the diagnosis and for excluding oligodendroglioma. PLNTY should be considered as a benign tumor corresponding to WHO Grade I. The prognosis is overall good after complete tumor-resection.

IgG4-related disease: a contemporary review

Background/aimImmunoglobulin G4-related disease (IgG4-RD), is an immune-mediated fibroinflammatory condition, which may involve multiple organs and mostly presents with high serum IgG4 levels and specific histopathological characteristics. As IgG4-RD is a relatively new entity the etiology, prevalence and epidemiologic knowledge is quite limited. Although involvement of almost all anatomical regions has been reported, the most commonly affected regions are pancreas, lacrimal glands, salivary glands, retroperitoneum, orbita, lymph nodes, kidney and lungs. Diagnosis is made with combined evaluation of clinical, radiological and histopathological findings. Typical histopathological features include storiform fibrosis, dense lymphoplasmacytic infiltrates and obliterative phlebitis. Its course is typically marked by remission and relapsing attacks and it may lead to fibrosis, destructive lesions in tissues and organ failure unless promptly treated. In the treatment of IgG4-RD, many approaches including surgical resection of tissues, systemic glucocorticoids, steroid-sparing immunosuppressive drugs, and biological agents are employed. Although association is not clear, malignancies are frequently reported in IgG4-RD patients. Therefore, it is prudent to monitor patients for the symptoms of malignant diseases.ConclusionIn this review, recent advances in clinico-pathological characteristics, diagnosis, and treatment of IgG4–RD are discussed.

Clinico-pathological Diagnosis of Transmissible Venereal Tumour with Hepatozoon canis and Babesia canis Infection in a Chippiparai Dog

Background: The concurrent infection of tick borne haemoprotozoan diseases like B.canis, E.canis and H.canis were commonly recorded in breed dogs. There is paucity in recording the combined haemoprotozoan infection with neoplasms in the native breeds of Tamil Nadu. The current investigation was documented to study the clinico-pathological changes, diagnosis and treatment of the concomitant infection of Hepatozoon canis and Babesia canis along with transmissible venereal tumor in a native dog.Methods: This Clinical investigation was carried out during April’ 2019 for about a month. A male Chippiparai dog was presented to the Veterinary Clinical Complex, VCRI, Tirunelveli with history of mass and bleeding from the genital area. The impression cytology from the mass and the whole blood and serum samples were collected for the laboratory diagnosis.Result: The hematological examination showed marked anaemia and the blood smear revealed the presence of H.canis gamonts in neutrophils and B.canis piroplasm in red bloods cells. The serum biochemical values showed the elevation of alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, creatinine and reduction of total protein, albumin. The impression cytology revealed the presence of uniform sheets discrete round cells with punctuate vacuolation in the cytoplasm, confirmed the sexually transmitted venereal tumor.

Diagnostic Criteria for Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation.

ObjectiveThe aim of the study was to describe the features required for diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM).Materials and MethodsThe International Society of the Study of Vulvovaginal Diseases tasked the difficult pathologic diagnoses committee to develop consensus recommendations for clinicopathologic diagnosis of vulvar lichen planus, lichen sclerosus, and dVIN. The dVIN subgroup reviewed the literature and formulated diagnostic criteria that were reviewed by the committee and then approved by the International Society of the Study of Vulvovaginal Diseases membership.ResultsDifferentiated vulvar intraepithelial neoplasia is the immediate precursor of human papillomavirus (HPV)–independent vulvar squamous cell carcinoma and shows a spectrum of clinical and microscopic appearances, some overlapping with HPV-related neoplasia. The histopathologic definition of dVIN is basal atypia combined with negative or nonblock-positive p16 and basal overexpressed, aberrant negative, or wild-type p53. The most common pattern of dVIN is keratinizing with acanthosis, aberrant rete ridge pattern, and premature maturation. The morphologic spectrum of keratinizing dVIN includes hypertrophic, atrophic, acantholytic, and subtle forms. A few dVIN cases are nonkeratinizing, with basaloid cells replacing more than 60% of epithelium. Vulvar aberrant maturation is an umbrella term for lesions with aberrant maturation that arise out of lichenoid dermatitis and lack the basal atypia required for dVIN.ConclusionsEvaluation of women at risk for dVIN and VAM requires a collaborative approach by clinicians and pathologists experienced in vulvar disorders. Close surveillance of women with lichen sclerosus and use of these recommendations may assist in prevention of HPV-independent squamous cell carcinoma through detection and treatment of dVIN and VAM.

Clinicopathological characteristics, diagnosis, and treatment of 29 cases of signet ring cell carcinoma of the rectum and sigmoid colon

Objective: To investigate the clinicopathological characteristics and the therapeutic effects of signet ring cell carcinoma (SRCC) of rectum and sigmoid colon. Methods: Clinical data and the follow-up information of 29 SRCC patients treated in our tertiary care center from 2008 to 2018 were retrospectively reviewed. The clinicopathological features, diagnostic and therapeutic effects, and the prognostic outcomes were analyzed. Results: Among the 29 patients, 17 were male, 12 were female. The average age was (48.7±14.3) years. Colonoscopy revealed the features of diffuse circumferential thickening of the bowel wall in 20/29 cases (69.0%), while in 9/29 cases (31.0%), endoscopic biopsies showed false negative results. Twenty-five% (4/16) and 17.6% (3/17) lesions were misdiagnosed as the inflammatory changes by endoscopic rectal ultrasonography exam and rectal MRI scan, respectively. Thirteen of the 29 patients received the neoadjuvant chemoradiotherapy (NCRT), 27 patients underwent the radical resection surgeries, and 8 underwent the postoperative radiotherapy. With a median follow-up of 38.5 (3.5-87.0) months, the cumulative 3-years overall survival (OS) rate was 54.0%, and the cumulative 3-years disease-free survival (DFS) rate was 43.0%. The OS rates of patients treated with or without NCRT (non-NCRT) were 46.2% and 69.2%, respectively, without significant difference (P>0.05). The DFS rates of patients treated with or without NCRT were 45.8% and 39.2%, respectively, without significant difference (P>0.05). Parameters including age younger than 40 years and tumor size larger than 5 cm were independent potential risk factors for shortened OS (P<0.05). Conclusions: SRCC of the rectum and sigmoid colon is a rare malignant tumor with special clinical manifestations. It is younger-onset, highly malignant and with very poor prognosis. Therefore, in-depth researches with focus upon the progress of molecular oncology are urgently needed to substantially improve the therapeutic effect of this disease.

Clinicopathologic Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation.

The aim of the study was to describe the demographic, clinical, and histopathologic features of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM). Specimens from 2010 to 2020 reported as dVIN or VAM were reviewed. Clinical data included age, rurality, symptoms, and evidence of lichen sclerosus (LS). Histopathologic data included epithelial thickness, keratinization, architectural and dyskeratotic features, stroma, p16, and p53. Differentiated vulvar intraepithelial neoplasia and VAM were distinguished by assessment of basal nuclear chromatin, enlargement, pleomorphism, and mitoses. One hundred twenty women with a median age of 71 years had 179 examples of dVIN and VAM. Squamous cell carcinoma was concurrent in 66% and associated with rurality. Ten percent were asymptomatic, and all but 3 had evidence of LS. Differentiated vulvar intraepithelial neoplasia showed a range of thickness, architecture, and dyskeratosis; its unifying !feature was basal atypia. Differentiated vulvar intraepithelial neoplasia displayed hyperchromasia in 83% and easily observed mitoses in 70%. Nonkeratinizing morphology, subcategorized into basaloid and intermediate, occurred in 24% of women with dVIN. Traditional dVIN represented 62% of keratinizing cases; the remainder were atrophic (13%), hypertrophic (13%), acantholytic (8%), or subtle (5%). Vulvar aberrant maturation had abnormal stratum corneum, acanthosis, premature maturation, and enlarged vesicular nuclei. Null p53 helped distinguish dVIN from VAM and dermatoses. The morphology of dVIN encompasses nonkeratinizing and keratinizing types, the latter subdivided into traditional, acantholytic, atrophic, hypertrophic, and subtle. Diagnosis relies on basal atypia with supportive p16 and p53. Atypia exists on a biologic spectrum with mild abnormalities of VAM and reactive change. Identification of dVIN and VAM requires collaboration between clinicians and pathologists experienced in vulvar disorders.

Diagnosis and Treatment of 43 Patients with IgG4-related Disease

To summarize the clinicopathological characteristics, diagnosis and treatment of IgG4-related disease (IgG4-RD). The clinical data of 43 cases with IgG4-RD diagnosed from January 2013 to December 2017 were retrospectively analyzed. The clinical data of the patients including clinical characteristics, accessory examinations, diagnosis, and treatment were collected. Among the 43 patients with IgG4-RD, the ratio of male to female was 3∶1, the mean age was (51.3±15.9) years. Eleven patients had gastrointestinal symptoms, including 5 cases of IgG4-related cholangitis with the feature of dilation of the biliary system and narrowing of the lumen in the abdominal enhanced CT scans, and 6 cases of IgG4-related autoimmune pancreatitis with the feature of pancreatic enlargement or soft tissue density shadow in the abdominal enhanced CT scans. There were 10 cases (23.3%) with periorbital involvement, with the feature of intraorbital soft tissue nodule in the CT scan. Besides, 9 cases (20.9%) had lymphadenopathy, 6 cases (14.0%) had fever. The results of autoimmune antibody tests showed that 14 of 42 patients had increased antinuclear antibody (ANA). Among 40 patients who underwent immunoglobulin tests, 25 cases had elevated IgG, 12 cases had increased IgA, and 29 cases had increased IgE. Coombs test were performed for 6 cases and 4 patients were positive. Serum immunoglobulin G4 subtypes showed that the IgG4 levels of 35 patients were higher than 1 350 mg/L. The immunohistochemistry showed that IgG4 (+) cells (3->500/HPF) were infiltrated, with the CD20 (+), CD3ε (+) or CD138 (+). Among the 43 patients, 5 patients underwent operations due to misdiagnosis. All patients were treated with steroid and immunosuppressive agents after diagnosis, and their clinical symptoms were improved. The clinical symptoms of IgG4-RD are various, involving multiple organs. Therefore, the standardized diagnosis and treatment of IgG4-RD should be strengthened.

Nasal meningoencephalocele: A retrospective study of clinicopathological features and diagnosis of 16 patients

ObjectiveNasal meningoencephalocele (encephalocele or cephalocele) is a rare condition with congenital, traumatic, or spontaneous origins. We investigated the clinicopathological characteristics of nasal encephaloceles to improve pathologists' and clinicians' understanding of this disease. MethodsSixteen patients with nasal encephaloceles were enrolled in this retrospective study investigating the condition's clinical and morphological features. ResultsPatients' average age was 37.8 (±20.8) years. The ratio of men to women was 2.2:1, patients' mean age was 47.4 (±11.8) years, and 10/16 patients had spontaneous encephaloceles. All patients with traumatic and spontaneous encephaloceles presented with cerebrospinal fluid leak. In 9/16 patients, the skull defect site occurred on the lateral wall of the sphenoid sinus. Both congenital patients experienced nasal obstruction. Histopathology, herniated tissues were brain and/or meningeal tissue, and the brain tissue was almost mature glial tissue. ConclusionNasal meningoencephalocele is a rare condition that can be challenging to diagnose. In patients with recurrent clear nasal discharge or in children with a unilateral nasal mass, a high index of suspicion for encephalocele is essential. In this study, spontaneous cases were most common in adults, and the lateral wall of the sphenoid sinus was the most common location.

Malignant gastrointestinal neuroectodermal tumor: clinicopathological analyses of four cases

Objective: To investigate the clinicopathological features, diagnosis, differential diagnosis, and molecular alterations of malignant gastrointestinal neuroectodermal tumor (MGNET). Methods: Four cases of MGNET were collected at Fujian Provincial Hospital, from July 2013 to January 2019. H&E and immunohistochemical staining were retrospectively evaluated, together with genetic mutation analysis of EWSR1. The relevant literature was systematically reviewed. Results: There were two male and two female patients, with an age range of 34-81 (median 57) years. Tumor sizes ranged from 5-9 (median 6.8) cm. Microscopy showed diffuse and flaky growth of tumor cells, some of which were small and round. The tumor cells were arranged in solid, flaky, nested or pseudoadenoid patterns. The tumor cells were epithelioid, oval, short spindled, or small, with round or oval nuclei. The cytoplasm was eosinophilic or clear. Osteoclast-like multinucleated giant cells were scattered focally. Mitosis was about (2-10)/10 HPF. Immunohistochemically, the tumor cells were positive for S-100 protein (4/4), SOX10 (4/4), Syn (2/4), INI1 (4/4), H3K27Me3 (4/4) and vimentin (4/4). Ki-67 index was 15%-90%. Gene mutation detection confirmed EWSR1 mutation in all four cases, and C-KIT/PDGFRα genes were not mutated in two cases. Conclusions: MGNET is a rare high grade malignant soft tissue tumor. The diagnosis is based on clinicopathological, immunophenotypic, and molecular pathology features. The primary treatment for MGNET is complete surgical excision and chemotherapy; the prognosis is poor.

Diagnostic value of MRI-derived liver surface nodularity score for the non-invasive quantification of hepatic fibrosis in non-alcoholic fatty liver disease.

To assess the accuracy of MRI-derived liver surface nodularity (LSN) score for staging of hepatic fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Forty-seven patients with clinicopathological diagnosis of NAFLD who underwent 1.5-T liver MRI within 12months of liver biopsy were included. Axial non-contrast T1-weighted 3D GRE was used for image analysis. LSN of the left lobe was measured using a custom semiautomated software. Histopathologic analysis (F0-F4) served as the reference standard for staging of fibrosis. Mann-Whitney test and Spearman's correlation coefficient were used to compare LSN scores between different stages of fibrosis and to assess the correlation. Diagnostic performance of LSN score for detection of significant (F2-F4) and advanced (F3-F4) fibrosis was assessed by receiver operating characteristics (ROC) curve. p value of less than 0.05 was considered statistically significant different. Twenty-one subjects had advanced fibrosis. The LSN scores among different stages of fibrosis were significantly different (p < 0.001). The correlation between LSN score and stage of fibrosis was also strong (ρ = 0.71; p < 0.001). The areas under ROC curves for detection of significant and advanced fibrosis were 0.80 (95% CI 0.66-0.95) and 0.86 (95% CI 0.75-0.97), using a threshold of 2.23 and 2.44, respectively. This method showed 81% sensitivity and 88% specificity for detection of advanced fibrosis. MR-based LSN score is a promising non-invasive objective tool for detection of advanced fibrosis in patients with NAFLD. • Liver surface nodularity (LSN) score is a fast retrospective method for precise quantification of nodularity of liver surface. • MR-based LSN score is a promising non-invasive objective tool to accurately detect different stages of fibrosis in patients with non-alcoholic fatty liver disease (NAFLD).

ADNC-RS, a clinical-genetic risk score, predicts Alzheimer's pathology in autopsy-confirmed Parkinson's disease and Dementia with Lewy bodies.

Growing evidence suggests overlap between Alzheimer's disease (AD) and Parkinson's disease (PD) pathophysiology in a subset of patients. Indeed, 50-80% of autopsy cases with a primary clinicopathological diagnosis of Lewy body disease (LBD)-most commonly manifesting during life as PD-have concomitant amyloid-beta and tau pathology, the defining pathologies of AD. Here we evaluated common genetic variants in genome-wide association with AD as predictors of concomitant AD pathology in the brains of people with a primary clinicopathological diagnosis of PD or Dementia with Lewy Bodies (DLB), diseases both characterized by neuronal Lewy bodies. In the first stage of our study, 127 consecutive autopsy-confirmed cases of PD or DLB from a single center were assessed for AD neuropathological change (ADNC), and these same cases were genotyped at 20 single nucleotide polymorphisms (SNPs) found by genome-wide association study to associate with risk for AD. In these 127 training set individuals, we developed a logistic regression model predicting the presence of ADNC, using backward stepwise regression for model selection and tenfold cross-validation to estimate performance. The best-fit model generated a risk score for ADNC (ADNC-RS) based on age at disease onset and genotype at three SNPs (APOE, BIN1, and SORL1 loci), with an area under the receiver operating curve (AUC) of 0.751 in our training set. In the replication stage of our study, we assessed model performance in a separate test set of the next 81 individuals genotyped in our center. In the test set, the AUC was 0.781, and individuals with ADNC-RS in the top quintile had four-fold increased likelihood of having AD pathology at autopsy compared with those in each of the lowest two quintiles. Finally, in the validation stage of our study, we applied our ADNC-RS model to 70 LBD individuals from 20 Alzheimer's Disease Research Centers (ADRC) whose autopsy and genetic data were available in the National Alzheimer's Coordinating Center (NACC) database. In this validation set, the AUC was 0.754. Thus, in patients with autopsy-confirmed PD or DLB, a simple model incorporating three AD-risk SNPs and age at disease onset substantially enriches for concomitant AD pathology at autopsy, with implications for identifying LBD patients in which targeting amyloid-beta or tau is a therapeutic strategy.

Abstract B01: Validation of a novel cytologic biomarker for urothelial carcinoma

Abstract Introduction: Cytology and cystoscopy have limited sensitivity and specificity for the diagnosis of urothelial carcinoma (UC), due to inflammatory atypia, sampling errors, and other clinicopathologic factors that may obscure test results. Therefore, there remains a clinical need to identify biomarkers to improve the diagnostic accuracy to detect UC. Keratin 17 (K17) is an embryologic cytokeratin that functions as an oncoprotein to promote the degradation of tumor suppressors that drive tumorigenesis. Published work from our group established that K17 is highly expressed in UC and confirmed specificity for UC by immunohistochemical localization of K17 in tissue biopsies of both low-grade and high-grade UCs (Babu et al., Mod Pathol, 2018). Objective: The objective of the current study was to develop an immunocytochemical (ICC) assay to determine K17 is a sensitive and specific biomarker to enhance diagnostic accuracy for UC in urine cytology. Methods: 80 ThinPrep CytoLyt-fixed urine specimens, collected at Stony Brook Medicine in 2018, including 39 with a clinicopathologic diagnosis of UC based on current cytologic diagnosis, and/or a history of biopsy confirmed UC within one year (+/-) of urine cytology specimen collection. K17 ICC was performed by indirect immunoperoxidase methods and K17 test results were scored based on the detection of immunoreactive urothelial cells and not on an assessment of cytologic atypia. The sensitivity and specificity of urine K17 ICC for detection of urothelial neoplasia was calculated by comparison of ICC test results with the cytologic diagnosis and/or the histologic diagnosis of positive cystoscopic biopsy specimens (papillary urothelial neoplasm of low malignant potential [PUNLMP, n=1] or greater). Samples that had no history of abnormal urine cytologic or biopsy diagnosis were categorized as negative for urothelial neoplasia. Results: Relative to the final clinicopathologic diagnosis of UC (n=38) or PUNLMP (n=1), K17 ICC had a sensitivity of 100% (95% CI: 91-100%) and specificity of 90% (95% CI: 77-96%). The positive predictive value was 90% (95% Cl: 78-96%) and the negative predictive value was 100% (95% Cl: 90-100%). Comparing ICC test results to cytologic and biopsy diagnoses, K17 ICC was positive in 9/23 (39%) cases with negative urine cytology. Of these 9 cases, 4 cases had biopsy confirmed UC. K17 ICC was positive in 4/11 (36%) of cases with inflammatory/reactive changes. Of these 4 cases, 3 had biopsy-confirmed UC. K17 ICC was positive in 14/30 (46%) of cases with mild atypia. Of these 14 cases, 12 had biopsy-confirmed UC and 1 had PUNLMP. K17 ICC was positive in 16/16 (100%) of cases with moderate atypia (n=8), severe atypia (n=3), or UC (n=5), all with biopsy-confirmed UC. Conclusions: K17 ICC is a novel and highly sensitive and specific diagnostic test for underlying biopsy-confirmed UC among samples with inflammatory/reactive changes, cytologic atypia, or positive urine cytology. Thus, the K17 test could serve as an adjunct to guide the clinical management of UC cases. Citation Format: Sruthi Babu, Lucia Roa-Peña, Ina Chan, Nam W. Kim, Sholeh Jahanfard, Luisa F. Escobar-Hoyos, Kenneth R. Shroyer. Validation of a novel cytologic biomarker for urothelial carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B01.

Diagnostic Significance of Clinicopathological Concordance in Various Spectrums of Skin Disorders

Introduction: Wide spectrums of skin disorders exist in the world. Skin biopsy is a proven method for allying the dermatologist in overcoming the diagnostic dilemmas that occur in consultations. The different level of clinicopathological concordance, either full or partial and discordant study may reflect the agreement between the clinicians and pathologists for diagnosing spectrum of skin disorders.&#x0D; Objectives: To analyze the histopathological spectrum of skin diseases emphasizing on the diagnostic significance of its clinicopathological concordance.&#x0D; Methodology: This is a prospective cross sectional hospital based study of skin biopsies obtained in the Department of Pathology, at Birat Medical College and Teaching Hospital from Dec 2016 to Jan 2020. Demographic data, nature of lesions, correlation between clinicopathological concordance and histopathological diagnosis were analyzed using SPSS version 16.&#x0D; Result: Among 111 skin biopsies, female gender of 19-39 years age groups was predominant. The commonest histopathological diagnosis of skin biopsies was under infectious and bacterial origin category (24.3%) reflecting non-neoplastic nature mostly. The overall clinicopathological concordant was 78.38% (fully concordant 27.93% and partially concordant 50.45%) and discordant 21.62%. Nature of lesions was strongly correlated (p&lt;0.05) with age group, while it was weak with gender. However, the relationship was very strong between histopathological diagnosis and clinicopathological concordance (p&lt;0.05%).&#x0D; Conclusion: Findings suggest that the clinicopathological concordance correlated well in histopathologically diagnosed disease category of skin disorders. This reflects the high diagnostic value of histopathological examinations for diagnosing different spectrum of skin disorders.

IgG4 plasma cell myeloma: Clinicopathological characteristics and diagnosis.

Plasma cell myeloma (PCM) is usually associated with the presence of M-protein in the serum and urine of patients, and about half of the PCM cases exhibit the IgG M-protein and increased gamma-globulin fraction on membrane electrophoresis. The IgG4 subclass is located in the beta-2 fraction on membrane electrophoresis. The aim of this study was to develop a method to evaluate IgG4-producing PCM (IgG4-PCM) and its clinicopathological characteristics. We found three cases of IgG4-PCM among 80 cases of IgG-producing PCM by membrane electrophoresis, which were confirmed by IgG4 immunostaining. None of the cases had a clinical history of IgG4-related disease, although they exhibited high levels of serum IgG4. A bone marrow aspiration specimen had an increased number of plasma cells with a relatively mature morphology. No cases exhibited lymphoplasmacytic inflammation, obliterative phlebitis or fibrosis. Immunohistochemistry revealed that tumor cells expressed CD138 and IgG4 and showed monoclonal expression of kappa. We revealed that IgG4-PCM might not be associated with IgG4-related disease and that the detection of M-protein with beta-globulin fraction by electrophoresis may be useful for screening IgG4-PCM.

Bronchiolar adenoma: a clinicopathological analysis of 15 cases

Objective: To study the clinicopathological characteristics, diagnosis and differential diagnosis of bronchiolar adenoma (BA). Methods: Fifteen cases of BA were collected from the First Affiliated Hospital of Nanjing Medical University, from January 2016 to October 2019. The clinical data, imaging examination, morphology, immunostaining and molecular changes were retrospectively analyzed. Results: There were 3 males, 12 females, most of the patients were female, mainly in middle-aged to elderly (51-77 years). Three had smoking history. The patients usually had no clinical symptoms. Imaging findings were ground-glass and/or lobulated nodules. Grossly, the tumors were gray-whitish, taupe solid or focally microcystic nodules with distinct boundary but no capsule. The maximum diameter was 0.4-2.5cm (mean 1.0cm). Histologically, there were glandular, papillary, or flat patterns that were composed of basal cells, mucous cells, ciliated cells and type Ⅱ pneumocytes, some of which showed basal cell proliferation and squamous cell metaplasia. However, there were some cases with few or even without mucous and/or ciliated cells. Immunostaining highlighted the continuous basal cell layer (positive for p63, p40 and cytokeratin 5/6), which was the most important diagnostic evidence. Genetic tests did not show mutation in BRAF or EGFR genes. All patients were followed up for 1-41 months, and they were without recurrence or metastasis. Conclusions: BA is a benign neoplasm that develops in the peripheral lung with good prognosis. Definite diagnosis is very crucial for surgical treatment, especially in frozen consultation. Immunohistochemistry will be helpful if necessary.

Clinicopathological differential diagnosis of IgG4‐related disease: A historical overview and a proposal of the criteria for excluding mimickers of IgG4‐related disease

IgG4-related disease (RD) is a relatively new entity, which was first proposed in 2001. Since then, clinical and pathological characteristics of the disease have been investigated. As IgG4-RD has been studied extensively, the diagnostic criteria for IgG4-RD of each organ and the comprehensive diagnostic criteria for IgG4-RD have also been developed. However, one of the biggest challenges in the field is distinguishing between IgG4-RD and mimickers, which show overlapping features with IgG4-RD. It is now known that some non-IgG4-RDs may meet the diagnostic criteria of IgG4-RD and can be misdiagnosed as IgG4-RD. However, accurate diagnosis is crucial, as the treatments for IgG4-RD and those for other diseases that may be misdiagnosed as IgG4-RD are different. This prompted us to create and propose comprehensive exclusion criteria for IgG4-RD. In this review, we have described the comprehensive exclusion criteria for IgG4-RD, with a historical overview of the disease. These exclusion criteria were recently created by the Research Program for Intractable Disease of the Ministry of Health, Labor, and Welfare of Japan, All Japan IgG4 team, to support correct and accurate diagnosis of IgG4-RD.

Paraganglioma of urinary bladder: a clinicopathological features analysis of 23 cases

Objective: To investigate the clinicopathological features, diagnosis, differential diagnosis and immunohistochemical (IHC) characteristics of paraganglioma of urinary bladder (PUB). Methods: The clinical and pathological data of 23 cases of PUB were collected at the Second Affiliated Hospital of Fujian Medical University (7 cases); Fujian Provincial Hospital (8 cases); Fujian Medical University Union Hospital (6 cases); and First Affiliated Hospital of Fujian Medical University (2 cases) from May 2010 to November 2018. IHC staining for CK, GATA3, CD56, Syn, CgA, S-100 protein, HMB45, SDHB, OCT3/4 and Ki-67 was done using EliVision method; and the relevant literature was reviewed. Results: There were 14 women and 9 men, aged ranged from 21 to 73 years (median 51 years). Clinically, patients presented with headache, vertigo, palpitation, hypertensive crisis during micturition, hypertension, blurred vision, gross hematuria and paroxysmal pallor. The tumor sizes ranged from 0.9 to 6 cm (mean2.5 cm). Macroscopically, most tumors were exophytic and well delineated within the lamina propria or muscularis propria. The tumors were firm and nodular and showed grayish-tan cut surface. Histologically,the tumor growth pattern was expansive or showed interpenetrating infiltrative growth within the lamina propria or muscularis propria; the tumor cells were typically arranged in distinctive nests (Zellballen) with organoid arrangement; pseudo-rosette were seen in some cases. The cells were rounded or polygonal and had rich, acidophilic or amphophilic cytoplasm and may contain pigmented granules and vacuoles; the nuclei were central or eccentric, with small nucleoli, although occasionally some nuclei were pleomorphic and hyperchromatic. Spindled sustentacular cells could be seen around the nests of tumor cells in some cases. There were abundant vessels that were fissure-like, hemangioma-like or dilated. By IHC, the tumor cells were positive for GATA3 (2/23), OCT3/4 (2/23), CD56 (22/23), Syn (23/23), CgA (22/23), S-100 (sustentacular cell, 23/23) and SDHB (23/23); and negative for CK and HMB45; Ki-67 index was 1%-5%. At follow-up, there was no recurrence or metastasis in 18 cases. Conclusions: The diagnosis of PUB relies on the morphologic and IHC features; but there may be histomorphologic heterogeneity. The most important differential diagnosis is invasive urothelial carcinoma. The tumor cells may show aberrant cytoplasmic expression of OCT3/4; there is no clear correlation between SDHB and OCT3/4 expression in the group.

Large nested variant of urothelial carcinoma of urinary bladder: a clinicopathological analysis of five cases

Objective: To investigate the clinicopathologic features, diagnosis and differential diagnosis of large nested variant of urothelial carcinoma (LNUC) of urinary bladder. Methods: The clinical and pathologic data of five cases of LNUC of urinary bladder diagnosed between January 2014 and December 2018 at the Department of Pathology, Zhejiang Provincial People's Hospital were analyzed by immunohistochemistry (IHC) and Sanger sequencing. The relevant literature was reviewed. Results: All five patients were male with a mean age of 63 years (range, 48 to 81 years). The mean tumor size was 3.4 cm (range, 1.7 to 4.7 cm). Histologically, the invasive LNUC tumor cells formed medium to large sized nests of varying shapes, from regular round, bulbous, oval to irregularly fused, branched, dumbbell shaped glands, with mild stromal reaction. In all five cases, focal central necrosis and microcystic changes in the tumor nests were identified. Cytologically, the tumor cells were low grade in four cases; the remaining case was overall low grade with focal high grade areas. Mitoses were scarce. All cases possessed surface urothelial tumors, including three low-grade papillary carcinomas, one high-grade papillary carcinoma and one carcinoma in situ. Three of the LNUC were accompanied by small nested variant of urothelial carcinoma and two by conventional high grade invasive urothelial carcinoma. Perineural involvement and angiolymphatic invasion were each noted in four tumors. Radical cystectomy was performed in four cases with TNM stages as followings: pT3aN0M0 in two cases, pT4aN0M0 and pT4aN1M0 in one case each. The remaining case had transurethral bladder resection and was of pT2 stage. By IHC, all five cases were positive for CK7 and p40; four were positive for GATA3; two were positive for CK20; and the mean Ki-67 proliferation index was 18%. TERT promoter mutation status were successfully performed in three cases, with one showing mutation (C228T) and two were wild type. All patients received postoperative chemotherapy. At a follow-up of 2 to 11 months, one patient died of unrelated causes, two patients developed metastases, and two were alive with no evidence of disease. Conclusions: LNUC is a histologic subtype of urothelial carcinoma with deceptively benign features but aggressive behavior, and appreciation of its unique infiltration patterns can aid in diagnosis and differential diagnosis. LNUC tends to coexist with small nested variant of urothelial carcinoma, suggesting these may represent different manifestations of the same urothelial carcinoma subtype.

Clinical characteristics and prognosis of multiple primary colorectal carcinoma

Objective To explore the clinical characteristics and prognosis of multiple primary colorectal carcinoma. Methods The clinical data of 42 cases of colorectal cancer admitted to the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2018 were retrospectively analyzed. The clinicopathological features, diagnosis, treatment and prognosis were summarized. Results There were 42 patients with multiple primary colorectal carcinoma, accounting for 1.20% (42/3 499) of all colorectal carcinoma patients in the same period. The main pathological type was adenocarcinoma. Among them, 32 cases were synchronous multiple primary carcinoma. And the age ranged 38-86 years old, and the median age was 66 years old. A total of 73 colorectal cancer lesions were detected, mostly located in the proximal colon, sigmoid colon and rectum. A total of 527 lymph nodes were detected, and the positive rate was 1.9% (10). Patients with positive lymph nodes accounted for 37.5% (12/32), including 27 cases of multiple primary carcinoma, 3 cases of triple primary carcinoma, 2 cases of five primary carcinoma. The 1-year and 3-year overall survival rates were 83.75% and 74.38%, respectively. There were 10 cases of metachronous multiple primary carcinoma. Patients were aged 33-86 years old. The first cancer was mostly located in the rectum and sigmoid colon, and the second cancer was mostly located in the ascending colon area. A total of 276 lymph nodes were detected, and the positive rate was 12.3% (34). The 1-year and 3-year overall survival rates were 100.00% and 66.67%, respectively. Conclusions Multiple primary colorectal cancer is not rare clinically and its distribution shows a certain regularity. More attention should be paid to improve the early diagnosis rate. Early operation is needed to improve the survival rate of patients. Key words: Colorectal neoplasms; Neoplasms, multiple primary; Clinical characteristics; Prognosis