Diagnostic Pathology

Extraosseous plasmacytoma, so called extramedullary plasmacytoma (EMP) is relatively rare in China. The aim was investigate the clinicopathologic features of EMP and the role of Immunophenotype and genotype detection in diagnosis of EMP. Thirty-two cases of EMP were investigated retrospectively by histopathology, immunophenotype, genotype and survival analysis. Clinically, the mean age of the patients was 53.4. Most of the patients received no treatment after the diagnosis was established, and the prognosis was relatively poor. Histologically, in 40% of the cases, the neoplastic cells were grade II or III. The neoplastic cells expressed one or more PC associated antigens. The immunophenotype of EMP and inflammation of sinonasal regions with numerous PC infiltrations were compared and showed some difference in expression of CD45, CD27, CD44v6 and Bcl-2 as well. Ig light chain restriction was detected in 87.5% of the cases. we described 32 Chinese cases of EMP, compare with that reported in the literature, some differences are presented, including higher percentage of grade II and III cases, clinically inconsistent treatment and management as well as poor outcome of the disease.

Surfactant Protein-A (SP-A) is the most prominent among four proteins in the pulmonary surfactant-system. SP-A is expressed by alveolar epithelial cells type II as well as by a portion of non small cell lung carcinomas (NSCLC). The expression of SP-A is complexly regulated on the transcriptional and the chromosomal level. SP-A is a major player in the pulmonary cytokine-network and moreover has been described to act in the pulmonary host defense. By the use of cell culture or animal models the functional properties have been repeatedly shown in many aspects, often bearing surprising properties which strongly indicate the physiological importance of SP-A. To date SP-A is recognized as a molecule essential for pulmonary development, structure and function. An upcoming number of reports deals with the role of SP-A for pulmonary pathology. This article gives an overview about the state of knowledge on SP-A focused in applications for human pulmonary disorders and points out the importance for pathology-orientated research approaches using immunohistochemistry or in situ hybridization as promising methods to further elucidate the role of this molecule in adult lung diseases.

Anaplastic lymphoma kinase (ALK) gene rearrangements, have been identified in approximately 2-7% of patients with lung adenocarcinoma (LUAD). However, co-occurrence of double ALK fusions in one patient was rare. Herein, we reported two Chinese female LUAD patients with confirmed double ALK fusion variants by next generation sequencing. Case 1, a 38-year-old female was diagnosed as peripheral LUAD in left upper lobe with synchronous multiple intrapulmonary metastases (pT2N0M1b, stage IVa). And case 2, a 58-year-old female had left lower lobe primary LUAD and synchronous multiple lung metastases (pT4N2M1b, stage IVa). In both patients, tumor cells displayed strong expression of ALK protein. Genetic profiling by next generation sequencing showed both patients concurrently harbored two types of ALK rearrangements. Case 1 had an unreported ALK-SSH2/EML4-ALK double fusions, and case 2 had an another novel ARID2-ALK/EML4‐ALK double fusions. Both of these patients responded to ALK inhibitor crizotinib. Our study reported two novel ALK fusion partners never reported, which expands the knowledge of ALK fusion spectrum and provides insight into therapeutic options for patients with double ALK fusions.

Lymphoma tế bào B lớn khuếch tán (DLBCL) thường dẫn đến sự thay đổi cấu trúc hạch bạch huyết do sự xâm lấn của các tế bào ác tính. Hiếm khi (<1%), DLBCL có thể xuất hiện với kiểu hình giữa các nang (DLBCL-IF) mà vẫn bảo tồn các nang bạch huyết. Người ta giả thuyết rằng DLBCL-IF có nguồn gốc từ các tế bào B vùng biên và có thể đại diện cho sự chuyển đổi tế bào lớn của lymphoma vùng biên (MZL), tuy nhiên chưa có bằng chứng trực tiếp nào được đưa ra cho đến nay. Ở đây, chúng tôi mô tả một trường hợp hiếm gặp của DLBCL-IF có tính chẩn đoán khó khăn liên quan đến một hạch bạch huyết ở một bệnh nhân có tiền sử hạch bạch huyết kéo dài nhiều năm và MZL liên quan đến da. Một người đàn ông 53 tuổi đã đến khám tại Phòng khám Da liễu của chúng tôi do có lịch sử ngứa toàn thân kéo dài một năm, mệt mỏi trong 2-3 tháng, buồn nôn và phát ban giữa lưng đã được sinh thiết. PET (hình ảnh phát xạ positron)/CT (chụp cắt lớp vi tính) đã được thực hiện và cho thấy tình trạng hạch bạch huyết ở bẹn, vùng chậu, sau phúc mạc, nách và cổ. Bệnh nhân được chuyển đến phẫu thuật để sinh thiết hạch bạch huyết bẹn phải. Các lát cắt nhuộm H&E chẩn đoán và các nghiên cứu bổ sung đã được xem xét cho mẫu hạch bạch huyết và da. Tính đồng nhất tế bào B thông qua PCR và các nghiên cứu giải mã đã được thực hiện trên cả hai mẫu. Chúng tôi chứng minh rằng MZL và DLBCL-IF của bệnh nhân này có liên quan đến tính đồng nhất, cho thấy một cách mạnh mẽ rằng sự chuyển đổi từ MZL sang DLBCL đã xảy ra. Hơn nữa, chúng tôi đã xác định được sự mất đoạn mới của cánh dài nhiễm sắc thể 20 (del(20q12)) và một đột biến điểm trong BIRC3 (Protein chứa miền lặp IAP virus Baculovirus 3) trong DLBCL của bệnh nhân này, vắng mặt trong MZL, cho thấy rằng những biến đổi di truyền này đã góp phần vào sự chuyển đổi thành tế bào lớn. Theo hiểu biết của chúng tôi, đây là báo cáo đầu tiên cung cấp bằng chứng phân tử cho mối liên hệ trước đây được nghi ngờ giữa MZL và DLBCL-IF. Ngoài ra, chúng tôi mô tả lần đầu tiên del(20q12) và đột biến điểm trong BIRC3 trong DLBCL. Phát hiện của chúng tôi cũng nâng cao nhận thức về DLBCL-IF và thảo luận về những cạm bẫy trong chẩn đoán của thực thể hiếm này.

To date, very few studies on clinical-histopathological correlations of cutaneous disorders associated with COVID-19 have been conducted. The Case 1 was a 90-year-old man, who tested positive for SARS-CoV-2 from a nasopharyngeal swab. Two days later, he was hospitalized and after eleven days transferred to Intensive Care Unit. A chest CT showed bilateral ground-glass opacities. Just that day, an erythematous maculo-papular rash appeared on trunk, shoulders and neck, becoming purpuric after few days. Histological evaluations revealed a chronic superficial dermatitis with purpuric aspects. The superficial and papillary dermis appeared edematous, with a perivascular lympho-granulocytic infiltrate and erythrocytic extravasation. At intraepithelial level, spongiosis and a granulocyte infiltrate were detected. Arterioles, capillaries and post-capillary venules showed endothelial swelling and appeared ectatic. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Regrettably, due to severe lung impairment, he died. The Case 2 was a 85-year-old man, admitted to Intensive Care Unit, where he was intubated. He had tested positive for SARS-CoV-2 from a nasopharyngeal swab two days before. A chest RX showed bilateral atypical pneumonia. After seven days, a cutaneous reddening involving trunk, upper limbs, neck and face developed, configuring a sub-erythroderma. Histological evaluations displayed edema in the papillary and superficial reticular dermis, and a perivascular lymphocytic infiltrate in the superficial dermis. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Sub-erythroderma as well as respiratory symptoms gradually improved until healing. The endothelial swelling detected in the Case 1 could be a morphological expression of SARS-CoV-2-induced endothelial dysfunction. We hypothesize that cutaneous damage could be initiated by endothelial dysfunction, caused by SARS-CoV-2 infection of endothelial cells or induced by immune system activation. The disruption of endothelial integrity could enhance microvascular permeability, extravasation of inflammatory cells and cytokines, with cutaneous injury. The Case 2 developed a sub-erythroderma associated with COVID-19, and a non-specific chronic dermatitis was detected at histological level. We speculate that a purpuric rash could represent the cutaneous sign of a more severe coagulopathy, as highlighted histologically by vascular abnormalities, while a sub-erythroderma could be expression of viral hematogenous spreading, inducing a non-specific chronic dermatitis.

We report a case of a 33-year-old man who presented with immunoglobulin (Ig)G4-related disease (IgG4-RD) forming a pseudotumor in the left paratesticular region during oral administration of corticosteroid for Wells syndrome, which involves cellulitis with eosinophilia. The patient was introduced to our institution from a private hospital with a 3-month history of asymptomatic left scrotal mass. A 5-cm diameter nodule was palpable in the left scrotum. Tumor lesion in the left paratestis involving the epididymis and spermatic cord was observed on computed tomography and magnetic resonance imaging. Blood testing showed no abnormalities other than a minimal increase in C-reactive protein levels. Urine examination likewise revealed no significant findings. Left radical orchidectomy was performed under a diagnosis of left paratesticular neoplasm suspected as malignant tumor. The tumor was pathologically identified as IgG4-RD of the left paratestis involving the epididymis and spermatic cord. We present a first description of IgG4-RD in a patient with Wells syndrome and the ninth case of IgG4-RD in a scrotal organ, and discuss this very rare entity with reference to the literature. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_225

Acetyl-CoA acetyltransferase 2 (ACAT2) is a lipid metabolism enzyme and rarely was researched in epithelial ovarian cancer (EOC). ACAT2 expressions were confirmed in two pairs of cell lines (A2780 and A2780/DDP, OVCAR8 and OVCAR8/DDP) from Gene Expression Omnibus database by bioinformatics analysis, and in A2780 and A2780/DDP cell lines by quantitative real-time polymerase chain reaction and western blotting. Tissue samples were stained by immunohistochemistry and scored for ACAT2 expression. The relationships between ACAT2 expression and clinicopathological characteristics were analyzed by χ2 test. The prognosis of ACAT2 was analyzed by the log-rank tests and Cox regression models. ACAT2 was remarkably upregulated in the above drug-resistant cell lines by mRNA (all P < 0.05) and protein expression (P = 0.026) than those in sensitive ones. Patients were classified as ACAT2-high (n = 51) and ACAT2-low (n = 26) according to immunohistochemical score. ACAT2 expression had a significantly inverse correlation with FIGO stage (P = 0.030) and chemo-response (P = 0.041). A marginal statistical significance existed in ACAT2 expression and ascites volume (P = 0.092). Univariate analysis suggested that high-expressed ACAT2 was associated with decreased platinum-free interval (PFI) (8.57 vs. 14.13 months, P = 0.044), progression-free survival (PFS) (14.12 vs. 19.79 months, P = 0.039) and overall survival (OS) (36.89 vs. 52.40 months, P = 0.044). Multivariate analysis demonstrated that ACAT2 expression (hazard ratio = 2.18, 95% confidence interval: 1.15–4.11, P = 0.017) affected OS independently, rather than PFI and PFS. The expression of ACAT2 in A2780/DDP and OVCAR8/DDP was higher than the corresponding A2780 and OVCAR8. High-expressed ACAT2 was associated with advanced FIGO stage, chemo-resistance, and decreased PFI, PFS and OS. It was an independent prognostic factor of OS in EOC.

Gastric-type endocervical adenocarcinoma is rare but the most common subtype of cervical adenocarcinoma not associated with human papillomavirus. It is more aggressive with a shorter five-year survival rate compared to human papillomavirus-associated usual type endocervical adenocarcinoma. The objectives of our study were to determine the incidence and clinical-pathological characteristics of Gastric-type endocervical adenocarcinoma in a single institution. Twenty four cases of invasive cervical adenocarcinoma were identified between January 2000 and December 2015, from the Saskatoon Health Region pathology database using International Endocervical Adenocarcinoma Criteria and Classification to retrospectively classify endocervical adenocarcinoma. Immunohistochemistry was performed with antibodies for Gastric mucin-6 (MUC-6), p16INK4a, cyclin-dependent kinase inhibitor 2A (p16), p53 protein (p53), estrogen and progesterone receptors. Clinical and pathological data was retrieved from pathology reports and charts. Statistical analysis was performed using Mann-Whitney U test and Chi-Square test. Using the International Endocervical Adenocarcinoma Criteria and Classification criteria, 19 cases (79.2%) were classified as human papillomavirus-associated usual type endocervical adenocarcinoma, and five cases (20.8%) as Gastric-type endocervical adenocarcinoma. In our study 40% of Gastric-type endocervical adenocarcinoma cases presented at stage III compared to none of the usual type endocervical carcinoma cases. All the Gastric-type endocervical adenocarcinoma cases were positive for MUC-6, and negative for p16. 60% Gastric-type endocervical adenocarcinoma cases demonstrated mutant type p53 staining. In contrast, 84.2% of human papillomavirus-associated usual type endocervical adenocarcinoma cases showed block like nuclear and cytoplasmic positivity with p16 antibodies. The Gastric-type endocervical adenocarcinoma group had significantly shorter median survival time than human papillomavirus-associated usual type endocervical adenocarcinoma group, Gastric-type endocervical adenocarcinoma is 22 months compared to human papillomavirus-associated usual type endocervical adenocarcinoma at 118 months (p = 0.043). In this study, Gastric-type endocervical adenocarcinoma accounted for 20.8% of all cervical adenocarcinoma with higher stage at presentation and shorter overall survival. Criteria proposed by International Endocervical Adenocarcinoma Criteria and Classification (IECC) are simple and reproducible in differentiating between, HPV- associated (HPVA) and non HPV associated (NHPVA) endocervical adenocarcinoma. Although none of the IHC assays is specific for GAS, but p16, MUC-6, ER, PR and p53 may further aid in confirming GAS and to differentiate it from benign and malignant mimics.