Absence of enhancement in a lesion does not preclude primary central nervous system T-cell lymphoma: A case report.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin lymphoma that originates in the central nervous system (CNS) and is exclusively limited to the CNS. Although most PCNSLs are diffuse large B-cell lymphomas, primary CNS T-cell lymphomas (PCNSTLs) are rare. PCNSTLs typically demonstrate some degree of enhancement on contrast-enhanced magnetic resonance imaging (MRI). To the best of our knowledge, non-enhancing PCNSTL has not been reported previously. CASE SUMMARY: A 69-year-old male presented to the neurology department with complaints of mild cognitive impairment and gradual onset of left lower leg weakness over a span of two weeks. Initial MRI showed asymmetric T2-hyperintense lesions within the brain. No enhancement was observed on the contrast-enhanced T1 image. The initial diagnosis was neuro-Behçet's disease. Despite high-dose steroid therapy, no alterations in the lesions were identified on initial MRI. The patient's symptoms deteriorated further. An MRI performed one month after the initial scan revealed an increased lesion extent. Subsequently, brain biopsy confirmed the diagnosis of PCNSTL. The patient underwent definitive combined chemo-radiotherapy. However, the patient developed bacteremia and died of septic shock approximately three months after diagnosis. CONCLUSION: The absence of enhancement in the lesion did not rule out PCNSTL. A biopsy approach is advisable for pathological confirmation.

Epithelioid angiomyolipoma of the liver in a patient with Li-Fraumeni syndrome: a case report.

BACKGROUND: Epithelioid angiomyolipoma (EAML) is a rare variant of angiomyolipoma that predominantly consists of epithelioid cells and belongs to the perivascular epithelioid cell neoplasm (PEComa) family. The majority of EAMLs arise in the kidneys, and primary hepatic EAML appears to be much less common than renal EAML. Most PEComas arise sporadically, but may be associated with tuberous sclerosis complex (TSC), an autosomal dominant genetic disorder characterized by germline mutations in the TSC1 or TSC2 genes. However, PEComas have previously been reported in five patients with Li-Fraumeni syndrome (LFS), which is an inherited cancer susceptibility disorder resulting from germline mutations in the TP53 tumor suppressor gene. CASE PRESENTATION: We report a 49-year-old female patient with hepatic EAML and pancreatic cancer. Because she had previously been diagnosed with bilateral breast cancer at the age of 30, we performed a comprehensive genetic analysis to identify genetic alterations associated with any cancer predisposition syndrome. Whole-exome sequencing of a blood sample identified a heterozygous germline variant of TP53 (NM_000546.5):c.708C>A, and targeted next-generation sequencing of liver EAML and pancreatic cancer tissue samples demonstrated the same TP53 (NM_000546.5):c.708C>A variant in both. This, plus the patient's history of early-onset breast cancer, met the 2015 version of the Chompret criteria for diagnosis of LFS. CONCLUSIONS: There have been very few case reports regarding the presence of PEComa in LFS, and to the best of our knowledge, this is the first report of EAML of the liver in a patient with LFS.

Cytokine storm syndrome after anti-thymoglobulin infusion in a cynomolgus monkey with systemic lymphadenopathy caused by follicular hyperplasia: A case report.

Nonhuman primates are widely used in transplantation research as preclinical xeno- or allo-transplantation models. Rabbit anti-thymoglobulin (ATG) is often used for T-cell depletion as an immunosuppressant. T-cell depletion can cause a secondary cytokine storm syndrome that can be minimized/prevented by a prophylactic administration of systemic corticosteroids and antihistamines. We report a case of death due to CSS in a cynomolgus monkey with follicular hyperplasia-induced systemic lymphadenopathy after ATG administration. A 6-year-old female cynomolgus monkey was rendered diabetic and then transplanted with a genetically modified porcine pancreatic islets (PPI) (50 000 IEQ/kg) through the portal vein 22 days later without immunosuppressant. Because graft function was not comparable, we planned re-transplantation of PPI. For re-transplantation of the PPI, we performed an intravenous (IV) ATG infusion for inductive immunosuppression. The monkey died 3 h and 30 min after ATG administration despite cardiopulmonary resuscitation. Systemic lymphadenopathy was observed on submandibular, axillary, inguinal, foregut, colic, and hilar lymph nodes, and splenomegaly was also observed on necropsy. Histopathologic examination of the lymph node revealed follicular hyperplasia. The IL-6 level was higher after ATG infusion compared to before ATG infusion (before vs. after ATG infusion; 14.9 vs. >5000 pg/mL). The death of the cynomolgus monkey was caused by severe CSS because of apoptosis of B cells in the systemic lymph nodes caused by the ATG administration. A thorough physical examination of palpable lymph nodes and pre-ATG sonographic or computed tomographic screening could have identified lymphadenopathy, potentially preventing its infusion and reducing mortality risk.

Effectiveness of antidepressant repetitive transcranial magnetic stimulation in a patient with refractory psychogenic dysphagia: A case report and review of literature.

BACKGROUND: Dysphagia is a common condition in older as well as young patients, and a variety of treatments have been reported depending on the cause. However, clinicians are challenged when the cause is unclear. This is the case with psychogenic dysphagia, which has typically been treated with supportive psychotherapy, medication, swallowing exercise, and dysphagia rehabilitation therapy. Here, we aimed to relieve the symptoms of a patient with refractory psychogenic dysphagia, who was unresponsive to conventional swallowing therapy, with repetitive transcranial magnetic stimulation (rTMS). CASE SUMMARY: A relatively calm-looking 35-year-old female patient presented with a 2-year history of dysphagia. She showed little improvement with conventional swallowing treatments over the past 2 years. She was relatively compliant with in-hospital dysphagia therapy, but uncooperative with home exercise and medication. In particular, since she was resistant to drug treatment, we had to take a different approach than the treatment she had been receiving for the past 2 years. After much deliberation, we decided to initiate antidepressant rTMS treatment with her consent (IRB No. 2023-05-021). Antidepressant rTMS treatment was performed twice weekly for a total of 20 sessions over 10 wk. The results showed improvement in subjective symptoms and video fluoroscopic swallowing study findings. To the best of our knowledge, this is the first report of symptomatic improvement using antidepressant rTMS protocol for refractory psychogenic dysphagia. CONCLUSION: This case demonstrates that rTMS with antidepressant protocol can be used to improve swallowing in patients with refractory psychogenic dysphagia.

MicroRNA 29a therapy for CEACAM6-expressing lung adenocarcinoma.

BACKGROUND: Non-coding microRNAs (miRNAs) play critical roles in tumor progression and hold great promise as therapeutic agents for multiple cancers. MicroRNA 29a (miR-29a) is a tumor suppressor miRNA that inhibits cancer cell growth and tumor progression in non-small cell lung cancer. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), which plays an important role in lung cancer progression, has been identified as a target of miR-29a. Here, we evaluated the therapeutic efficacy of a peptide vector capable of delivering miR-29a intracellularly using the acidic tumor microenvironment in a lung adenocarcinoma xenograft mouse model. METHODS: A miRNA delivery vector was constructed by tethering the peptide nucleic acid form of miR-29a to a peptide with a low pH-induced transmembrane structure (pHLIP) to enable transport of the miRNAs across the plasma membrane. Tumor suppressive effects of pHLIP-miR29a on lung adenocarcinoma development in vivo were assessed using a BALB/c xenograft model injected with A549 cells. RESULTS: Incubation of A549 cells with pHLIP-miR-29a at an acidic pH downregulated endogenous CEACAM6 expression and reduced cell viability. Intravenous injection of the mice with pHLIP-miR-29a inhibited tumor growth by up to 18.1%. Intraperitoneal injection of cisplatin reduced tumor volume by 29.9%. Combined pHLIP-miR-29a + cisplatin treatment had an additive effect, reducing tumor volume up to 39.7%. CONCLUSIONS: Delivery of miR-29a to lung adenocarcinoma cells using a pHLIP-mediated method has therapeutic potential as a unique cancer treatment approach.

Intrahepatic Cholangiocarcinoma Arising from Biliary Hamartomas in Patients with Recurrent Acute Cholangitis: A Case Report and Literature Review.

Biliary hamartomas are tumor-like malformations of the liver. Biliary hamartomas are a type of fibrocystic disorder originating from ductal plate malformation and are typically considered benign, but with the risk of malignant transformation. In this case report, we present a rare occurrence of intrahepatic cholangiocarcinoma (ICC) that developed from biliary hamartomas, along with a literature review. A 76-year-old man with a diagnosis of biliary hamartomas had a history of recurrent cholangitis for 12 years, necessitating cholecystectomy, ERCP, and repeated antibiotic treatments. During his last episode, imaging studies revealed a hypervascular infiltrative mass in the right posterior liver segment. A liver biopsy confirmed adenocarcinoma and subsequent surgical pathology revealed ICC originating from biliary hamartomas. Chronic inflammation in the bile duct associated with biliary hamartomas may serve as a potential trigger for malignant transformation, as observed in this case. Therefore, close surveillance is essential for patients with biliary hamartomas presenting with infectious complications.

Adenocarcinoma arising from heterotopic pancreas at the first portion of the duodenum: a case report.

Malignant transformation of a heterotopic pancreas in the duodenum is very rare. To our knowledge, only 15 cases have been reported worldwide, including the present case. We herein report a rare case of malignant transformation of a heterotopic pancreas in the duodenum along with a review of the literature.A 65-year-old man was admitted to our hospital for evaluation of dyspepsia and vomiting. Esophagogastroduodenoscopy showed a stricture of the duodenal bulb. Laparoscopic distal gastrectomy was performed. Although a duodenal tumor had not been suspected, histopathological examination of the surgical specimen showed adenocarcinoma arising from a heterotopic pancreas (Heinrich type III) in the duodenum. Four months postoperatively, the patient received adjuvant chemotherapy. He was still alive without recurrence at 24 months of follow-up.Adenocarcinoma arising in a heterotopic pancreas is rare; therefore, preoperative diagnosis is difficult to obtain. Effective management of a heterotopic pancreas depends on the presence or absence of symptoms. Awareness of the possibility of malignant change in a heterotopic pancreas of the duodenum prior to surgery is helpful for the diagnosis and appropriate management of such patients.

Clinicopathological Characteristics of Autoimmune-Like Hepatitis Induced by COVID-19 mRNA Vaccine (Pfizer-BioNTech, BNT162b2): A Case Report and Literature Review.

Widespread use of vaccinations worldwide in the coronavirus disease (COVID-19) pandemic has resulted in various side effects. Here, we presented a 27-year-old man with autoimmune-like hepatitis after the first dose of the BNT162b2 (mRNA) COVID-19 vaccine and reviewed previous reports. He presented with sweating, febrile sensations, and general weakness. He did not have any medical histories. Although he was treated with biphenyl dimethyl dicarboxylate and ursodeoxycholic acid, the elevated liver enzyme levels persisted for 2 months. Liver biopsy demonstrated portal inflammation with rosette formation, interface hepatitis, and infiltration of lymphocytes, histiocytes, plasma cells, and eosinophils. Especially, centrilobular edema and necrosis were found. The symptoms and liver enzymes improved with prednisolone treatment. If persistently elevated liver enzymes are found after COVID-19 mRNA vaccination, the possibility of autoimmune-like hepatitis induced by the vaccine should be considered and a careful pathologic evaluation is required.

Inflammatory myofibroblastic tumor of the urinary bladder with FN1­ALK gene fusion: A case report.

Inflammatory myofibroblastic tumors (IMTs), which are rare tumors, exhibit myofibroblastic differentiation, often with anaplastic lymphoma kinase (ALK) gene rearrangements. A subset of IMTs identified in the urinary tract have been shown to harbor a fibronectin 1 (FN1)-ALK gene fusion. In this case report, a case of an IMT with FN1-ALK fusion in the urinary bladder was presented, and its clinicopathological characteristics were reviewed. A 45-year-old female was referred to Chungbuk National University Hospital with gross hematuria. Cystoscopy revealed a solid mass in the bladder. The patient subsequently underwent transurethral resection of the lesion. The mass comprised stellate and spindled myofibroblastic cells that were arranged in loose fascicles, with a myxoid background and a mixed inflammatory infiltrate. Immunohistochemical analysis revealed that the tumor cells were positive for vimentin, cytokeratin AE1/AE3 and ALK, and focal-positive for desmin. Targeted next-generation sequencing was subsequently employed to identify the FN1-ALK fusion. To date, the patient has undergone outpatient follow-up for 18 months, with no signs of tumor recurrence. To conclude, in total, FN1 has been identified as an ALK fusion partner almost exclusively in cases of genitourinary IMTs [13 bladder IMTs (including the present case) and two uterine IMTs]. In the present case, the FN1-ALK fusion was found to involve ALK exon 19 and FN1 exon 23. By contrast, the majority of the other IMTs with an ALK fusion have involved ALK exon 20, whereas ALK fusion involving ALK exon 18 or 19 has been reported only in genitourinary IMTs. Therefore, the FN1-ALK fusion involving ALK exon 18 or 19 may be specific to a subset of IMTs arising in the urinary bladder.

Primary retroperitoneal mucinous cystic neoplasm of borderline malignancy with KRAS and GNAS co-mutation: a case report.

Primary retroperitoneal mucinous cystic neoplasms are rare retroperitoneal tumors, which are histologically similar to mucinous cystic neoplasms of the ovaries. Only 31 cases of primary retroperitoneal mucinous cystic neoplasm with borderline malignancy (PRMCN-BM) have been reported (26 in women and five in men). We describe an additional male patient with PRMCN-BM. A 39-year-old man presented to our hospital with back pain. Twelve years earlier, he had undergone an orchiectomy for a germ cell tumor. Computed tomography showed a 6.9- × 4.4-cm cystic mass in the left pararenal space. Laparoscopic mass excision was performed, and a unilocular cystic mass was found in the pararenal space near the lower pole of the left kidney. A histopathological examination showed a cyst lined by atypical mucinous intestinal epithelium without stromal invasion. Targeted next-generation sequencing identified two hotspot mutations, with one each in the KRAS and GNAS genes. Outpatient follow-up 10 months after surgery showed no evidence of tumor recurrence. PRMCNs are extremely rare retroperitoneal neoplasms, especially in men. These neoplasms are rarely considered in the differential diagnosis of retroperitoneal masses, and their preoperative diagnosis is difficult. Evaluation of additional patients is required to better determine the prognosis of PRMCNs and the optimal postoperative follow-up.

Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea.

BACKGROUND: Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study. METHODS: Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53. RESULTS: CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history. CONCLUSIONS: Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

Altered Lung Heat Shock Protein-70 Expression and Severity of Sepsis-Induced Acute Lung Injury in a Chronic Kidney Disease Rat Model.

Enhanced heat shock protein-70 (HSP-70) expression in the lungs is associated with attenuated acute lung injury (ALI) in a sepsis model. Chronic kidney disease (CKD) significantly contributes to the poor prognosis of patients with sepsis. This study examined the relationship between sepsis-induced ALI severity and altered lung HSP-70 expression in CKD. Experimental rats underwent a sham operation (control group) or 5/6 nephrectomy (CKD group). Sepsis was induced with cecal ligation and puncture (CLP). Laboratory tests and lung harvest were performed in the control group (without CLP and after 3, 12, 24, and 72 h of CLP) and in the CKD group (without CLP and after 72 h of CLP). ALI was the most severe after 12 h of sepsis. The mean lung injury score at 72 h after sepsis was significantly higher in the CKD group than in the control group (4.38 versus 3.30, p < 0.01). Nonetheless, enhanced lung HSP-70 expression was not observed in the CKD group. This study shows that altered lung HSP-70 expression is associated with the worsening of sepsis-induced ALI in patients with CKD. Enhancing lung HSP-70 is a novel treatment target for patients with CKD and sepsis-induced ALI.

pSlugS158 Immunohistochemistry is Useful in Grading Meningioma.

Snail family transcriptional repressor 2 (SNAI2, Slug) is a transcription factor that belong to the Slug/Snail superfamily. Site specific phosphorylation of slug (pSlugS158) is detected during the M phase, and thus, this phosphorylated protein is considered a novel marker for detecting mitotic figures. Herein, we investigated whether the detection of mitosis using pSlugS158 expression can be used in the histological grading of meningioma. We performed immunohistochemistry for pSlugS158 and PHH3 in tissue samples of 61 patients with meningioma and examined the association between mitotic counts using pSlugS158 and recurrence-free survival (RFS). The nuclear expression of pSlugS158 was observed in the cell with mitotic figures. Tumor grading based on pSlugS158 was significantly associated with the RFS (p < .001). It can be concluded that pSlugS158 is a useful and practical marker to detect mitosis and seems to be reliable for the counting of mitoses in histological grading of meningioma.

Diagnostic Value of Nestin Expression in Adult Gliomas.

Introduction. Nestin, a type VI intermediate filament, is expressed in neuroepithelial cells during embryogenesis and has been expressed in various human tumors. Recent studies reported that the expression was associated with poor prognosis in brain tumors, but the results were inconclusive. In this study, we evaluated usefulness of nestin expression as a prognostic biomarker in consideration of IDH mutation and the World Health Organization (WHO) classification fifth edition. Methods. To investigate nestin expression, immunohistochemistry was performed on 92 adult brain gliomas using tissue microarrays. We analyzed the clinical characteristics and survival outcomes according to nestin expression and examined whether nestin expression alone affects the prognosis, independent of IDH mutation. Results. Sixty patients (65.2%) were nestin-positive (weak and strong). Nestin expression and intensity were significantly correlated with pathologic diagnosis and IDH mutation. The patients with high-grade gliomas showed a higher frequency and stronger intensity of nestin expression than those with low-grade gliomas (P < .001). The majority (93.6%) of gliomas with IDH mutation showed no expression or weak positivity. Multivariate Cox proportional hazard regression analysis for overall survival demonstrated that nestin expression (weak, hazard ratio [HR] 5.39, P = .036; strong, HR 8.43, P = .007) was an independent prognostic factor. Moreover, patients with nestin-expressing glioma showed shorter survival (P < .001). Conclusions. Nestin seems to be strongly expressed in the vast majority of glioblastomas, IDH-wildtype and rarely in IDH-mutant gliomas. Clear correlation between nestin expression and pathologic diagnosis makes an accurate patient diagnosis. Expression and intensity of nestin were significantly correlated with worse survival.

Ampullary gangliocytic paraganglioma with lymph node metastasis: A case report with literature review.

RATIONALE: Gangliocytic paraganglioma (GP) is a rare tumor that mostly develops in the duodenum and is composed of the following 3 cell types: epithelioid endocrine, spindle-like, and ganglion-like cells. It manifests as symptoms such as abdominal pain, gastrointestinal bleeding, and weight loss; however, occasionally, it is incidentally detected on endoscopic or radiologic examinations. Although GP is usually benign, it can metastasize to the lymph nodes, and distant metastases have been reported in some cases. PATIENT CONCERNS: A 46-year-old woman presented with anemia on health surveillance examination. She had no other specific symptoms, and her physical examination did not reveal any abnormal finding. DIAGNOSIS: Endoscopic ultrasound-guided fine-needle aspiration biopsy was performed, and the endoscopist obtained samples from the inner side of the ampullary mass. Pathological examination suggested GP or a neuroendocrine tumor. INTERVENTIONS: Initially, we planned transduodenal ampullectomy with lymph node excision. However, there was severe fibrosis around the duodenum, and an examination of a frozen biopsy sample from the periduodenal lymph node showed atypical cells in the lymph node. Therefore, we performed pylorus-preserving pancreaticoduodenectomy with lymph node dissection. OUTCOMES: The final pathological diagnosis was GP located in the ampulla of Vater. The GP showed lymphovascular and perineural invasion and invaded the duodenal wall. Furthermore, 4 out of 18 harvested lymph nodes showed metastasis. LESSONS: We described a case of GP confined to the ampulla with regional lymph node metastasis and reviewed published literature on ampullary GP with lymph node metastasis.

Clinicopathological Characteristics of Inflammatory Myositis Induced by COVID-19 Vaccine (Pfizer-BioNTech BNT162b2): A Case Report.

As more individuals were coronavirus disease 2019 (COVID-19) vaccinated, unexpected side effects appeared. Herein, we present the case of a 30-year-old man with myopathy in both extremities after the second dose of the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine. Symptoms, swelling and pain, started from the proximal upper and lower extremities and extended to the distal parts. Although he underwent massive hydration, the muscle enzyme level continuously increased. He complained of dysphagia and dysarthria. Microscopically, muscle biopsy showed multifocal or scattered macrophage infiltration and degenerated myofibers. In contrast to general myopathy including inflammatory myositis and rhabdomyolysis, vaccine-induced inflammatory myositis shows a prolonged increase in muscle enzyme levels and multifocal macrophage infiltration with necrosis of the muscle fibers. Symptoms improved with glucocorticoid and immunosuppressive treatment. If vaccinated individuals experience severe and continuous muscle pain and swelling, clinicians should consider vaccine-induced inflammatory myositis, measure the muscle enzyme levels, and perform muscle biopsy for a definite diagnosis.

Acute aspiration pneumonia in common marmoset (Callithrix jacchus) with marmoset duodenal dilation syndrome: A case report.

A female common marmoset (Callithrix jachhus) suffered from weight loss exhibited tachypnea after anesthesia. We diagnosed marmoset duodenal dilation syndrome (MDDS) and aspiration pneumonia after post-anesthesia vomiting secondary to MDDS. If MDDS is suspected due to clinical symptoms such as weight loss, bloating, or vomiting, careful anesthesia and treatment of vomiting will be important to prevent aspiration pneumonia.

Pulmonary vein aneurysm in a New Zealand White rabbit: a case report.

BACKGROUND: Pulmonary venous aneurysm (PVA) is a rare condition characterized by aneurysmal dilatation of the pulmonary vein in humans. The diagnosis is incidental usually as there are no clinical symptoms. This case report describes a histological diagnosis of PVA in a New Zealand White rabbit. CASE PRESENTATION: A 1.5-kg male New Zealand White rabbit was acclimatized in an animal room for 5 weeks until the experiment began. However, the rabbit was found dead, with signs of nasal hemorrhage. Necropsy revealed tracheal and pulmonary hemorrhage, and the epistaxis had a pulmonary origin. PCR and ELISA to detect antigens and antibodies pertaining to the rabbit hemorrhagic disease virus showed negative results. Multiple ballooning lesions (50-200 µm size) in the pulmonary veins were observed on histological examination, and PVA was diagnosed. Death was attributed to a spontaneous rupture of the PVA and massive hemorrhage into the lung parenchyma that extended into the trachea and nasal passages. CONCLUSIONS: To the author's best knowledge, this is the first report of a PVA in a rabbit.

Histologic Changes in Non-Small Cell Lung Cancer under Various Treatments: A Comparison of Histology and Mutation Status in Serial Samples.

PURPOSE: Histologic change is a resistant mechanism in lung cancer. The most common histological change is the switch from adenocarcinoma (AdenoCa) to small cell carcinoma (SCC) against to tyrosine kinase inhibitors (TKI). However, it is not clear whether other treatment modalities are involved in the histologic changes. MATERIALS AND METHODS: We investigated histological changes in eight cases, after various treatments, and compared the molecular profiles between primary tumors and changed tumors using exome sequencing where tissue was available. RESULTS: Three cases of AdenoCa that were changed into SCC retained the initial mutations after TKI and/or surgical treatment. After treatment with TKI and immunotherapy, an EGFR (epidermal growth factor receptor)-mutant AdenoCa changed to squamous cell carcinoma (SqCa). SqCa in a patient treated with surgery was changed into combined AdenoCa and SqCa. These two cases showed the same genetic variations between the two distinct non-small cell carcinomas (NSCC). Three patients experienced two histologic changes, which the changed tumors returned to its original subtype or changed to a combined tumor after treatments. Four cases showed combined histology in the first or second change. CONCLUSION: The histology of NSCC can be changed to a single pattern or combined subtypes after various treatment modalities, and the phenotypic changes seem not fixed. Therefore, additional morphologic changes may occur regardless of their genetic status and types of treatments. To refine the new treatment strategy, consecutive repeated biopsies in progressive disease or recurrent tumor are necessary.

pSlugS158 immunohistochemistry is a novel promising mitotic marker for FFPE samples: a pilot study.

Slug is a transcription factor belonging to the slug/snail superfamily. The protein is involved in embryonic development and epithelial-mesenchymal transition of tumors. Slug is also under temporal regulation during cell cycle. Here, we examined relationship between pSlugS158 (site-specific phosphorylation) and the cell cycle, and checked whether its phosphorylation level reflects mitotic activity in tissue specimens. Cell cycle analysis was performed after cell synchronization. To evaluate pSlugS158 identifying mitotic figures, we performed immunohistochemistry (IHC) for pSlugS158 in various formalin-fixed paraffin-embedded tissues; in addition, mitotic counts were compared with those in sections stained with hematoxylin and eosin (HE) and IHC for PHH3, a mitotic marker. We found that the level of pSlugS158 protein increased specifically at M phase and decreased at the G1/S phases in vitro. In almost all tested tissues, nuclear stain of pSlugS158 was identified in the cell with mitotic figures. There was no significant difference in mitotic counts between HE- and pSlugS158-stained sections. In conclusion, pSlugS158 may be a novel and practical immunohistochemical marker for detecting mitotic figures in human tissues.