Aberrant expression of GATA3 in metastatic adenocarcinoma of the prostate: an important pitfall.

AIMS: The distinction of high-grade prostate cancer (PCa) from poorly differentiated urothelial carcinoma (UC) can be somewhat challenging on clinical and morphological grounds alone, yet it is of great importance for prognostication and choice of treatment. GATA3 is a useful immunohistochemical marker to confirm urothelial origin. However, recent works report strong GATA3 immunoexpression in primary high-grade PCa. The aim of this study was to explore GATA3 expression specifically in metastatic PCa. METHODS AND RESULTS: The pathology databases of four tertiary institutions were queried for cases of metastatic PCa. Available slides and clinical records were reviewed by experienced genitourinary pathologists. Prostatic markers (PSA, PSAP, NKX3.1) and GATA3 immunohistochemistry were performed. A total of 163 metastatic PCa cases were included. At least one prostate marker was positive in each case of non-regional distant metastasis, confirming prostatic origin. GATA3 strong staining was found in four (2.5%) cases: two liver, one bone and one non-regional lymph-node metastases. All four patients had Grade Group 5 PCa at the initial diagnosis. The metastatic prostatic adenocarcinomas were solid, either with no gland formation (n = 3) or with only focal cribriforming (n = 1). CONCLUSIONS: To our knowledge, this is the first study exploring GATA3 expression specifically in metastatic PCa. Despite being infrequent, GATA3 positivity in high-grade PCa may lead to misdiagnosis, with clinical implications. We recommend a panel of immunohistochemical markers, both prostatic and urothelial, for ruling out UC, either in primary tumour samples or in the event of metastases of unknown primary, when a genitourinary origin is suspected.

Emerging roles of transmembrane-type tight junction proteins in cancers.

Tight junctions (TJs) are the most apical components of the cell-cell adhesion machinery in epithelial and endothelial cells and they play essential roles in homeostasis. Recent studies have revealed that aberrant expression of tight junction proteins (TJPs) is frequently observed in various type of cancers. Here we review cancer-associated aberrant expression of TJPs with focus on transmembrane-type TJPs including claudins, junctional adhesion molecule-A (JAM-A), and occludin. Some transmembrane-type TJPs are upregulated at the early neoplastic stage and their expression persists during dedifferentiation. Aberrant expression of TJPs contributes to proliferation, invasion, and dysregulated signaling of cancer cells. In addition to an increase in their expression level, their localization is altered from a TJ-restricted pattern to distribution throughout the whole cell membrane, making them suitable as therapeutic targets. Extracellular domains of transmembrane-type TJPs can be approached by target drugs not only from the lumen side (apical side) but also from the extracellular matrix side (basal side), including blood vessels. Aberrantly expressed TJPs are potential useful diagnostic markers as well as therapeutic targets for cancers.

Primary central nervous system extranodal NK/T-cell lymphoma, nasal type with CD20 expression: Case report and review of the literature.

Primary central nervous system (PCNS) extranodal NK/T-cell lymphoma, nasal type (ENKTCL), is an exceedingly rare tumor. To the best of our knowledge, only 27 cases and only one reported aberrant CD20 expression have been documented in the literature. Here we present a second case of PCNS ENKTCL with aberrant CD20 expression in a 43-year-old immunocompetent Chinese female. The patient presented with tremors, weakness in the right upper limb, and a slow reaction. Magnetic resonance imaging revealed multiple brain lesions. A histological examination revealed a diffuse distribution of intermediate-sized pleomorphic lymphocytes with angiocentric growth. The tumor cells expressed CD2, CD3, CD56, T-cell intracellular antigen-1, granzyme B, and Epstein-Barr virus-encoded RNAs (EBERs), with additional partial and weak CD20 and CD30 expression. Despite a confirmatory pathological diagnosis, the patient refused treatment and was discharged, ultimately dying from the disease. In the literature review, the clinical, immunohistochemical, EBERs, treatment, and prognostic features of PCNS ENKTCL were summarized. Although PCNS ENKTCT is extremely rare, it does occur and should always be included in differential diagnoses. CD20 expression should be evaluated routinely with relevant markers. The accumulation of cases is crucial for developing an effective treatment strategy for this rare and aggressive malignancy.

The Role of Paxillin Aberrant Expression in Cancer and Its Potential as a Target for Cancer Therapy.

Paxillin is a multi-domain adaptor protein. As an important member of focal adhesion (FA) and a participant in regulating cell movement, paxillin plays an important role in physiological processes such as nervous system development, embryonic development, and vascular development. However, increasing evidence suggests that paxillin is aberrantly expressed in many cancers. Many scholars have also recognized that the abnormal expression of paxillin is related to the prognosis, metastases, invasion, survival, angiogenesis, and other aspects of malignant tumors, suggesting that paxillin may be a potential cancer therapeutic target. Therefore, the study of how aberrant paxillin expression affects the process of tumorigenesis and metastasis will help to develop more efficacious antitumor drugs. Herein, we review the structure of paxillin and its function and expression in tumors, paying special attention to the multifaceted effects of paxillin on tumors, the mechanism of tumorigenesis and progression, and its potential role in tumor therapy. We also hope to provide a reference for the clinical prognosis and development of new tumor therapeutic targets.

The impact of NRG1 expressions and methylation on multifactorial Hirschsprung disease.

BACKGROUND: Hirschsprung disease (HSCR) is a complex genetic disorder characterized by the lack of ganglion cells in the intestines. A current study showed that the NRG1 rare variant frequency in Indonesian patients with HSCR is only 0.9%. Here, we investigated the impact of NRG1 expressions and methylation patterns on the pathogenesis of HSCR. METHODS: This cross-sectional study determined NRG1 type I (HRGα, HRGß1, HRGß2, HRGß3, HRGγ, and NDF43 isoforms), type II and type III expressions in both ganglionic and aganglionic colons of 20 patients with HSCR and 10 control colons by real-time polymerase chain reaction (qPCR). For methylation studies, we treated the extracted gDNA from 16 HSCR patients' and 17 control colons with sodium bisulfate and analyzed the methylation pattern of NRG1 exon 1 with methylation-specific PCR. The samples were collected and analyzed at our institution from December 2018 to December 2020. RESULTS: NRG1 types I, II and III expressions were upregulated (17.2-, 3.2-, and 7.2-fold, respectively) in the ganglionic colons compared with control colons (type I: 13.32 ± 1.65 vs. 17.42 ± 1.51, p < 0.01; type II: 13.73 ± 2.02 vs. 16.29 ± 2.19, p < 0.01; type III: 13.47 ± 3.01 vs. 16.32 ± 2.58, p = 0.03; respectively); while only type I (7.7-fold) and HRGß1/HRGß2 (3.3-fold) isoforms were significantly upregulated in the aganglionic colons compared to the controls (type I: 14.47 ± 1.66 vs. 17.42 ± 1.51, p < 0.01; HRGß1/HRGß2: 13.62 ± 3.42 vs 14.75 ± 1.26, p = 0.01). Moreover, the frequency of partially methylated NRG1 was higher in the ganglionic (81%) and aganglionic (75%) colons than in the controls (59%). CONCLUSIONS: Our study provides further insights into the aberrant NRG1 expression in the colons of patients with HSCR, both ganglionic and aganglionic bowel, which might contribute to the development of HSCR, particularly in Indonesia. Furthermore, these aberrant NRG1 expressions might be associated with its methylation pattern.

Aberrant expression of myeloid antigens in patients of acute lymphoblastic leukaemia.

OBJECTIVE: To determine the immunophenotypic pattern and aberrant expression of myeloid antigens in newly diagnosed patients of acute lymphoblastic leukaemia(ALL). METHODS: This descriptive cross-sectional study was carried out in Haematology / Pathology department, Army Medical College, National University of Medical Sciences (NUMS) in collaboration with Immunology and Haematology departments of Armed Forces Institute of Pathology (AFIP), Rawalpindi from 1st January, 2019 to 31st December, 2019. Seventy-three (73) recently diagnosed patients of Acute Lymphoblastic leukaemia of all age groups and both genders were included in the study. A proforma was used to note demographic data. CBC, cytochemical stains and bone marrow examinations were carried out and assessed for morphology and percentage of blasts using a microscope. Flow cytometry was used to perform immunophenotyping on samples of peripheral blood and bone marrow, using a standard panel. RESULTS: The most commonly expressed markers were weak CD45, TdT, CD19, CD10 and HLA-DR. Weak CD45 was present in almost all blast cells and there was no remarkable difference in its positivity among various subtypes of ALL. Myeloid expression was observed in 13 (17.8%) cases. CD13 and CD33 were aberrantly expressed in 11 and 12.3 of all cases of ALL respectively. CONCLUSIONS: Expression of aberrant myeloid CD markers in acute lymphocytic leukaemia has prognostic significance and should be documented during lineage assignment of acute leukaemias while performing immunophenotyping.

Long noncoding RNAs in endometriosis: Biological functions, expressions, and mechanisms.

Endometriosis refers to a benign chronic gynecological disorder, and is defined as the ectopic growth of endometrium in pelvic cavity. Endometriosis affects about 10% of reproductive-aged women. Unfortunately, the pathogenesis of endometriosis remains obscure, and the disease witnesses a lack of effective therapy approaches. Therefore, more research needs to be performed to throw light on endometriosis, its pathogenesis, and therapy. Long noncoding RNAs (lncRNAs), which are defined as functional cellular RNA longer than 200 nucleotides, have been implicated in many chronic disorders. It has been suggested that lncRNAs are closely related to the endometriosis process. Nevertheless, the molecular mechanisms by which lncRNAs associate with endometriosis should be elucidated more detailed. In our brief review, we first exhibit the aberrant lncRNAs expression in endometriosis. Then, we talk about the molecular mechanisms underlying lncRNAs in endometriosis. Finally, we also present the potential of lncRNAs as biomarkers for endometriosis.

Systematic identification of dysregulated lncRNAs associated with platinum-based chemotherapy response across 11 cancer types.

Aberrant expression of long non-coding RNAs (lncRNAs) leads to the development of chemoresistance by regulating a series of biological processes, which is one of the major obstacles in the cancer treatment. This study aimed to identify some key lncRNAs that are associated with platinum-based chemoresistance in multiple cancers. Regulating the expression levels of these lncRNAs can enhance the sensitivity of patients to chemotherapy drugs and improve the therapeutic effect of cancer. By systematically analyzing 648 samples regarding platinum drug response from the Cancer Genome Atlas (TCGA), we have identified 32 dysregulated lncRNAs across 11 cancer types that could affect platinum-based chemotherapy response, of which 78.125% (25/32) were significantly down-regulated in drug-resistant samples. Drug response prediction model that had been constructed based on the expression pattern of these dysregulated lncRNAs could accurately predict the chemotherapy response of tumor patients, and the area under the curve (AUC) was between 0.8034 and 0.9984. In particular, all of these dysregulated lncRNAs that we identified were cancer-specific. They were significantly associated with the survival of tumor patients and could serve as cancer-specific biomarkers for prognosis. In conclusion, this study will contribute to improving the drug resistance of tumor patients during chemotherapy, and it is of real significance for selecting effective chemotherapy drugs and achieving precision medicine.

The pathogenic role of the GIP/GIPR axis in human endocrine tumors: emerging clinical mechanisms beyond diabetes.

The glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone produced in the gastrointestinal tract in response to nutrients. GIP has a variety of effects on different systems, including the potentiation of insulin secretion from pancreatic ß-cells after food intake (i.e. incretin effect), which is probably the most important. GIP effects are mediated by the GIP receptor (GIPR), a G protein-coupled receptor expressed in several tissues, including islet ß-cells, adipocytes, bone cells, and brain. As well as its involvement in metabolic disorders (e.g. it contributes to the impaired postprandial insulin secretion in type 2 diabetes (T2DM), and to the pathogenesis of obesity and associated insulin resistance), an inappropriate GIP/GIPR axis activation of potential diagnostic and prognostic value has been reported in several endocrine tumors in recent years. The ectopic GIPR expression seen in patients with overt Cushing syndrome and primary bilateral macronodular adrenal hyperplasia or unilateral cortisol-producing adenoma has been associated with an inverse rhythm of cortisol secretion, with low fasting morning plasma levels that increase after eating. On the other hand, most acromegalic patients with an unusual GH response to oral glucose suppression have GIPR-positive somatotropinomas, and a milder phenotype, and are more responsive to medical treatment. Neuroendocrine tumors are characterized by a strong GIPR expression that may correlate positively or inversely with the proliferative index MIB-1, and that seems an attractive target for developing novel radioligands. The main purpose of this review is to summarize the role of the GIP/GIPR axis in endocrine neoplasia, in the experimental and the clinical settings.

Expressional activation and functional roles of human endogenous retroviruses in cancers.

Human endogenous retroviruses (HERVs) are widely believed to be remnants of ancestral germ line infections by exogenous retroviruses. Although HERVs are deemed as "nonfunctional DNAs" due to loss of most of their viral protein coding capacity during evolution as part of the human genome, cumulative evidences are showing the expressional activation and potential roles of HERVs in diseases especially cancers. Work by other researchers and us has observed the dysregulation of HERVs in cancers, identified new HERV-related genes, and revealed their potential importance in cancer development. Here, we summarized the current knowledge on the mechanisms of the expressional activation and functional roles of HERVs, with a focus on the H family HERV (HERV-H), in carcinogenesis. HERV expression is regulated by external chemical or physical substances and exogenous virus infection, as well as host factors such as epigenetic DNA methylation, transcription factors, cytokines, and small RNAs. Diverse roles of HERVs have been proposed by acting in the forms of noncoding RNAs, proteins, and transcriptional regulators during carcinogenesis. However, much remains to be learnt about the contributions of HERVs to human cancers. More investigation is warranted to elucidate the functions of these "fossil remnants" yet important viral DNAs in the human genome.

The effect of APTR, Fn14 and CD133 expressions on liver fibrosis in biliary atresia patients.

PURPOSE: Although some biomarkers of hepatic progenitor cells have been reported to be involved in the liver fibrosis in patients with biliary atresia (BA), however, research still shows conflicting results. Therefore, we investigated the effect of Alu-mediated p21 transcriptional regulator (APTR), fibroblast growth factor-inducible 14 (Fn14) and CD133 expressions on liver fibrosis in Indonesian BA patients. METHODS: Nineteen liver samples from BA patients and 9 liver specimens from non-BA controls were obtained. The expressions of APTR, Fn14 and CD133 were analyzed by quantitative real-time polymerase chain reaction (qPCR). RESULTS: APTR expression was strongly up-regulated (1.5-fold) in liver BA specimens compared to liver controls (ΔCT 3.2 ± 0.6 vs 3.8 ± 0.51; p = 0.028). Moreover, Fn14 and CD133 expressions were similar in the BA and control groups (ΔCT 2.7 ± 1.3 vs. 1.4 ± 1.6, p = 0.07; and 12.0 ± 3.7 vs. 11.78 ± 2.30, p = 0.88, respectively). Intriguingly, CD133 expression was strongly related with the survival of BA patients (p = 0.0061), but not with age at Kasai procedure (p = 0.36) and the presence of cirrhosis (p = 0.77). CONCLUSION: We present the first study of aberrant APTR expressions in the liver of BA infants which might contribute to liver fibrogenesis in BA infants.

Aberrant UBR4 expressions in Hirschsprung disease patients.

BACKGROUND: Recently, pathogenic alleles within ubiquitin N-recognin domain-containing E3 ligase 4 (UBR4) gene have been shown to be associated with Hirschsprung disease (HSCR). We determined the UBR4 expressions in Indonesian HSCR patients. METHODS: We analyzed the UBR4 expressions in the colons of HSCR patient and anorectal malformation (ARM) patient as control by real-time polymerase chain reaction (qPCR). RESULTS: Thirty-seven patients with non-syndromic HSCR and eighteen controls were involved in this study. qPCR revealed that the UBR4 expression was strongly decreased (0.77-fold) in the ganglionic group of patients with HSCR compared to the control group with ARM (ΔCT 2.43 ± 0.36 vs. 2.05 ± 0.69; p = 0.009), whereas the UBR4 expression was also significantly reduced (0.79-fold) in the aganglionic group of patients with HSCR compared to the control group with ARM (ΔCT 2.39 ± 0.46 vs. 2.05 ± 0.69; p = 0.044). However, the UBR4 expression change was not associated with gender (p = 0.35 and 0.80), nor with degree of aganglionosis both in ganglionic and aganglionic colons (p = 0.72 and 0.73), respectively. CONCLUSION: Our study demonstrates that expression of UBR4 is decreased in both aganglionic and ganglionic colon of HSCR patients.

Expression of embryonic stem cell markers in acute myeloid leukemia.

Acute myeloid leukemia is driven by leukemic stem cells which can be identified by cross lineage expression or arrest of differentiation compared to normal hematopoietic stem cells. Self-renewal and lack of differentiation are also features of stem cells and have been associated with the expression of embryonic genes. The aim of our study was to evaluate the expression of embryonic antigens (OCT4, NANOG, SOX2, SSEA1, SSEA3) in hematopoietic stem cell subsets (CD34+CD38- and CD34+CD38+) from normal bone marrows and in samples from acute myeloid leukemia patients. We observed an upregulation of the transcription factors OCT4 and SOX2 in leukemic cells as compared to normal cells. Conversely, SSEA1 protein was downregulated in leukemic cells. The expression of OCT4, SOX2, and SSEA3 was higher in CD34+CD38- than in CD34+CD38+ subsets in leukemic cells. There was no correlation with biological characteristics of the leukemia. We evaluated the prognostic value of marker expression in 69 patients who received an intensive treatment. The rate of complete remission was not influenced by the level of expression of markers. Overall survival was significantly better for patients with high SOX2 levels, which was unexpected because of the inverse correlation with favorable genetic subtypes. These results prompt us to evaluate the potential role of these markers in leukemogenesis and to test their relevance for better leukemic stem cell identification.

Long noncoding RNAs and tumorigenesis: genetic associations, molecular mechanisms, and therapeutic strategies.

The human genome contains a large number of nonprotein-coding sequences. Recently, new discoveries in the functions of nonprotein-coding sequences have demonstrated that the "Dark Genome" significantly contributes to human diseases, especially with regard to cancer. Of particular interest in this review are long noncoding RNAs (lncRNAs), which comprise a class of nonprotein-coding transcripts that are longer than 200 nucleotides. Accumulating evidence indicates that a large number of lncRNAs exhibit genetic associations with tumorigenesis, tumor progression, and metastasis. Our current understanding of the molecular bases of these lncRNAs that are associated with cancer indicate that they play critical roles in gene transcription, translation, and chromatin modification. Therapeutic strategies based on the targeting of lncRNAs to disrupt their expression or their functions are being developed. In this review, we briefly summarize and discuss the genetic associations and the aberrant expression of lncRNAs in cancer, with a particular focus on studies that have revealed the molecular mechanisms of lncRNAs in tumorigenesis. In addition, we also discuss different therapeutic strategies that involve the targeting of lncRNAs.

[Space-occupying lesion in the maxillary sinus]. / Eine Raumforderung im Sinus maxillaris.

During the preoperative diagnostics of an 80-year-old male patient prior to a planned endarterectomy, an unclear space-occupying lesion was detected in the right nasopharyngeal cavity. It proved to be a dense soft tissue space-occupying lesion of the right maxillary sinus. The histological investigations revealed a partially necrotically decomposed malignant tumor below normal respiratory mucosa free from dysplasia. This case demonstrates the difficulties in differential diagnostics, particularly involving (aberrant) expression of cytokeratin.

Current strategies for early epithelial ovarian cancer detection using miRNA as a potential tool.

Ovarian cancer is one of the most aggressive and significant malignant tumor forms in the female reproductive system. It is the leading cause of death among gynecological cancers owing to its metastasis. Since its preliminary disease symptoms are lacking, it is imperative to develop early diagnostic biomarkers to aid in treatment optimization and personalization. In this vein, microRNAs, which are short sequence non-coding molecules, displayed great potential as highly specific and sensitive biomarker. miRNAs have been extensively advocated and proven to serve an instrumental part in the clinical management of cancer, especially ovarian cancer, by promoting the cancer cell progression, invasion, delayed apoptosis, epithelial-mesenchymal transition, metastasis of cancer cells, chemosensitivity and resistance and disease therapy. Here, we cover our present comprehension of the most up-to-date microRNA-based approaches to detect ovarian cancer, as well as current diagnostic and treatment strategies, the role of microRNAs as oncogenes or tumor suppressor genes, and their significance in ovarian cancer progression, prognosis, and therapy.

Aberrant expression of CD markers in AML in patients attending RIMS, Ranchi - An observational study.

Introduction: Acute myeloid leukaemia (AML) is a tumour of hematopoietic progenitors caused by acquired oncogenic mutations that impede differentiation, leading to the accumulation of immature myeloid blasts in the marrow. Aberrant phenotype is a phenomenon in which lymphoid-associated and other myeloid lineage markers are expressed in myeloblasts or myeloid-associated markers are expressed in lymphoblasts. Materials and Methods: Diagnosed cases of AML were included in this study to study the aberrant expression using multiparametric flow cytometry. Results: Out of a sample size of 50, 30 cases expressed aberrant CD markers. Male: Female ratio was 0.76. Majority of cases belonged to the age group >60 years of age. CD 7 was overall the most common aberrant CD marker. Conclusion: Immunophenotyping has a significant role in diagnosis and predicting prognosis of hematopoietic malignancies in the absence of more advanced diagnostic tools like cytogenetics.

Analysis of 3760 hematologic malignancies reveals rare transcriptomic aberrations of driver genes.

BACKGROUND: Rare oncogenic driver events, particularly affecting the expression or splicing of driver genes, are suspected to substantially contribute to the large heterogeneity of hematologic malignancies. However, their identification remains challenging. METHODS: To address this issue, we generated the largest dataset to date of matched whole genome sequencing and total RNA sequencing of hematologic malignancies from 3760 patients spanning 24 disease entities. Taking advantage of our dataset size, we focused on discovering rare regulatory aberrations. Therefore, we called expression and splicing outliers using an extension of the workflow DROP (Detection of RNA Outliers Pipeline) and AbSplice, a variant effect predictor that identifies genetic variants causing aberrant splicing. We next trained a machine learning model integrating these results to prioritize new candidate disease-specific driver genes. RESULTS: We found a median of seven expression outlier genes, two splicing outlier genes, and two rare splice-affecting variants per sample. Each category showed significant enrichment for already well-characterized driver genes, with odds ratios exceeding three among genes called in more than five samples. On held-out data, our integrative modeling significantly outperformed modeling based solely on genomic data and revealed promising novel candidate driver genes. Remarkably, we found a truncated form of the low density lipoprotein receptor LRP1B transcript to be aberrantly overexpressed in about half of hairy cell leukemia variant (HCL-V) samples and, to a lesser extent, in closely related B-cell neoplasms. This observation, which was confirmed in an independent cohort, suggests LRP1B as a novel marker for a HCL-V subclass and a yet unreported functional role of LRP1B within these rare entities. CONCLUSIONS: Altogether, our census of expression and splicing outliers for 24 hematologic malignancy entities and the companion computational workflow constitute unique resources to deepen our understanding of rare oncogenic events in hematologic cancers.

Transcribed ultraconserved region in human cancers.

Long non-coding RNAs (lncRNAs) are transcripts longer than ~200 nucleotides with little or no protein-coding capacity. Growing evidence shows that lncRNAs present important function in development and are associated with many human diseases such as cancers, Alzheimer disease, and heart diseases. Transcribed ultraconserved region (T-UCR) transcripts are a novel class of lncRNAs transcribed from ultraconserved regions (UCRs). UCRs are absolutely conserved (100%) between the orthologous regions of the human, rat, and mouse genomes. The UCRs are frequently located at fragile sites and at genomic regions involved in cancers. Recent data suggest that T-UCRs are altered at the transcriptional level in human tumorigenesis and the aberrant T-UCRs expression profiles can be used to differentiate human cancer types. The profound understanding of T-UCRs can throw new light on the pathogenesis of human cancers.

Malakoplakia with aberrant ALK expression by immunohistochemistry: a case report.

BACKGROUND: Malakoplakia is a rare inflammatory disease of the urogenital tract. There have been no reports of malakoplakia expressing anaplastic lymphoma kinase (ALK) to date. Here, we present one case of malakoplakia with aberrant ALK expression by immunohistochemistry and discuss the clinical significance. CASE PRESENTATION: A 65-year-old Chinese woman with a history of diabetes presented with solid masses in the liver and kidney and elevated lesions on the mucosal surface of the colon. Right nephrectomy and partial liver resection were performed. Microscopically, sheets of histiocytes with poor intercellular adhesion were seen, with Michaelis-Gutmann bodies present in both the intracellular and extracellular interstitium. CD10-, CD68-, and CD163-positive cells were present, with Michaelis-Gutmann bodies confirmed by staining with Alcian blue, periodic acid-Schiff (PAS), periodic acid-Schiff with diastase, Von Kossa, and Prussian blue. Aberrant ALK1 and ALK (D5F3) expression was observed in the cytoplasm and nucleus of cells. However, ALK gene mutation was not detected by fluorescence in situ hybridization or whole exome next-generation sequencing. NGS revealed nine individual somatic gene mutations: GOT1L1, GLIS2, SPOUT1, TMEM97, MUC3A, NSD2, SFXN5, ADAD1 and RAD50. The significance of the somatic gene mutations detected in this study is not clear, and the relationship between them and malakoplakia cannot be clarified by existing scientific studies. The pathological diagnosis was malakoplakia with aberrant ALK expression by immunohistochemistry. The antibiotics imipenem and vancomycin were started based on the results of drug sensitivity analysis and the patient was subsequently discharged. She experienced no discomfort during 30 months of follow-up. CONCLUSION: This is the first reported case of malakoplakia with aberrant ALK expression, it should be differentiated from ALK-positive histiocytosis to avoid misdiagnosis.