Immunocytochemistry on frozen-embedded cell block for the diagnosis of hematolymphoid cytology specimen: a straightforward alternative to the conventional cell block.

Agarose-based cell block (CB) technique can be modified to be combined with the frozen section technique for the preparation of a high-quality frozen-embedded CB (F-CB) from an effusion or fine-needle aspiration (FNA) cytology sample. This combined technique can be effectively used for the immunocharacterization of the hematolymphoid cells on F-CB. To demonstrate the applicability of performing diagnostic ICC on F-CB, we have analyzed the immunophenotype of the hematolymphoid cells in a series of eight cases of effusions and eight cases of FNA cytology specimens by using CB-ICC on sections cut from frozen-embedded CBs. The SurePathTM residue or cytologic material scraped off from the FNA cytology smear that was diagnostic for or suspicious of hematolymphoid malignancy was pelleted and pre-embedded in agarose. Half of the agarose-embedded pellet was frozen-embedded in OCT compound for the preparation of F-CB, while the other half was processed for the preparation of paraffin-embedded CB. Sections cut from the F-CB and P-CB were used for CB-ICC. Panels of ICC on the F-CBs could enable the immunocytochemical differential diagnosis of large cell hematologic malignancies that encompass anaplastic large cell lymphoma and other forms of large-cell hematolymphoid malignancies such as large B-cell lymphomas, anaplastic plasma cell myeloma, myeloid sarcoma, and T-lymphoblastic lymphoma. It also appeared that the small B-cell lymphomas in the effusions or FNAs could be differentially diagnosed with the aid of CB-ICC on the F-CB. A modified agarose-based CB technique can be combined with the frozen-embedded CB method for the preparation of F-CB that can be directly used for the immunocytochemical differential diagnosis of hematolymphoid cytology samples.

Comparative efficacies and safeties of cylindrical interstitial laser ablation and radiofrequency ablation on swine pancreas.

Laser ablation (LA) has been evaluated for the minimally invasive thermal treatment of various cancers, but conventional unidirectional endoscopic ultrasound (EUS)-guided LA has limitations. Therefore, we developed a cylindrical laser diffuser to overcome the limitations of unidirectional EUS-guided LA. The purpose of this study was to compare the efficacies and safeties of EUS-guided LA using a novel cylindrical laser diffuser and radiofrequency ablation (RFA) in vivo in swine pancreas. EUS-guided RFA (15 W, 30 s, 450 J) and cylindrical interstitial LA (CILA) (5 W, 90 s, 450 J) were applied to normal pancreatic tissue in six anesthetized pigs (three per group). Laboratory tests were performed at baseline, immediately after ablation (day 0), and 2 days after procedures (day 2). Two days after procedures, all pigs were sacrificed, and histopathological safety and efficacy assessments were performed. Technically, EUS-guided RFA and CILA were performed successfully in all cases. No major complications, including perforation or acute pancreatitis, occurred during the experiment in either group. All animals remained in excellent condition throughout the experimental period, and laboratory tests provided no evidence of a major complication. Average necrotic volumes in the RFA and CILA groups were 424.2 mm3 and 3747.4 mm3, respectively, and average necrotic volume was significantly larger in CILA group (p < 0.001). EUS-guided RFA and CILA had acceptable safety profiles in the normal swine pancreas model. Our findings indicate EUS-guided CILA has potential for the effective local treatment of pancreatic cancer as an alternative to EUS-guided RFA.

Seromucinous Hamartoma of the Sinonasal Cavity.

Benign tumors or malignant neoplasms must be evaluated in patients with unilateral nasal cavity mass lesions. The 3 most prevalent unilateral benign mass lesions in such individuals are nasal polyps (NPs) and inverted papillomas (IPs). Although rare, it should be kept in mind that sinonasal hamartomas can be occasionally diagnosed as well. Among sinonasal hamartomas, respiratory epithelial adenomatoid hamartoma is more prevalent, with seromucinous hamartoma (SMH) being the second most common. Unlike NPs, sinonasal hamartomas are benign tumors with growth potential, which means it should not be undertreated and warrants surgical removal for treatment. However, sinonasal hamartomas do not have local invasion or malignant transformation potential like IPs; hence, it is vital not to overtreat them. Therefore, understanding the histopathology of SMH and thereby establishing proper surgical planning prior to the surgery remains crucial in such cases. Here, we present a successfully treated case of SMH with a distinctive radiographic, gross, and pathological clinical image of SMH.

Cytological features of mesonephric-like adenocarcinoma of the uterine corpus.

BACKGROUND: Although several studies have documented the histological features of uterine mesonephric-like adenocarcinoma (MLA), its cytological features have been rarely reported. METHODS: We searched for histologically confirmed uterine MLA cases in the pathology archives of three institutions between 2010 and 2021. All available cytology slides were examined to identify the cytological features of uterine MLA. RESULTS: We included 16 patients with uterine MLA and reviewed the slides obtained from 21 cytology samples. Samples were obtained from the cervicovagina (9/21, 42.9%), peritoneal washing (8/21, 38.1%), pleural effusion (2/21, 9.5%), and transbronchial needle aspiration of mediastinal lymph node (2/21, 9.5%). Preparation methods included ThinPrep (11/21, 52.4%), SurePath (8/21, 38.1%), and conventional smear (2/21, 9.5%). Regardless of the sampling site and preparation method, cytology samples displayed tight three-dimensional cellular clusters showing monotonous, small-to-medium-sized, round, hyperchromatic nuclei, indistinct nucleoli, scant cytoplasm, and high nuclear-to-cytoplasmic ratio. Approximately half of the samples (10/21, 47.6%) showed hyaline-like globules. Mitotic figures (7/21, 33.3%) and apoptotic bodies (13/21, 61.9%) were also observed. No tumor diathesis or nuclear feathering was identified. CONCLUSIONS: Irrespective of sampling site and preparation method, the majority of uterine MLA cases showed the following cytological features: tight three-dimensional cellular clusters showing small-to-medium-sized, round, hyperchromatic nuclei with indistinct nucleoli and high nuclear-to-cytoplasm ratio. In case a cytology sample suspicious of a glandular lesion displays these cytological features, which are distinct from those of endocervical adenocarcinoma, uterine MLA should be included in the differential diagnosis.

Endoscopic Ultrasound-Guided Pancreatic Interstitial Laser Ablation Using a Cylindrical Laser Diffuser: A Long-Term Follow-Up Study.

BACKGROUND AND AIMS: Local ablative treatment is another option for improving outcomes and has been evaluated for locally advanced pancreatic cancer. We previously suggested endoscopic ultrasound (EUS)-guided interstitial laser ablation using a cylindrical laser diffuser (CILA) might be a feasible therapeutic option based on experiments performed on pancreatic cancer cell lines and porcine model with a short follow-up (3 days). The aim of this study was to investigate the safety of EUS-CILA performed using optimal settings in porcine pancreas with a long-term follow-up (2 weeks). METHODS: EUS-CILA (laser energy of 450 J; 5 W for 90 s) was applied to normal pancreatic tissue in porcine (n = 5) under EUS guidance. Animals were observed clinically for 2 weeks after EUS-CILA to evaluate complications. Computed tomography and laboratory tests were carried out to evaluate safety. Two weeks after EUS-CILA, all pigs were sacrificed, and histopathological safety and efficacy evaluations were conducted. RESULTS: EUS-CILA was technically successful in all five cases. No major complications occurred during the follow-up period. Body weight of porcine did not change during the study period without any significant change in feed intake. Animals remained in excellent condition throughout the experimental period, and laboratory tests and computed tomography (CT) scans provided no evidence of a major complication. Histopathological evaluation showed complete ablation in the ablated area with clear delineation of surrounding normal pancreatic tissue. Mean ablated volume was 55.5 mm2 × 29.0 mm and mean ablated areas in the pancreatic sections of the five pigs were not significantly different (p = 0.368). CONCLUSIONS: In conclusion, our experimental study suggests that EUS-CILA is safe and has the potential to be an effective local treatment modality. No major morbidity or mortality occurred during the study period. Further evaluations are warranted before clinical application.

The first report on effect of fecal microbiota transplantation as a complementary treatment in a patient with steroid-refractory Cronkhite-Canada syndrome: A case report.

RATIONALE: Cronkhite-Canada syndrome (CCS) is a rare non-hereditary disease of unknown etiology that is characterized by the appearance of multiple polyps in the entire gastrointestinal (GI) tract, except in the esophagus, with GI and non-GI symptoms. Various factors are associated with the pathogenesis of CCS. Immune dysregulation has been discussed as one of the pathogeneses of CCS, and dysbiosis of the gut microbiota can affect the immune system. Currently, standard treatment has not been established. PATIENT CONCERNS AND DIAGNOSIS: We present the treatment with fecal microbiota transplantation (FMT) in a 67-year-old male patient with steroid-refractory CCS who could not undergo anti-tumor necrosis factor-a treatment due to suspected tuberculosis infection. INTERVENTIONS: FMT has recently attracted attention as a method of overcoming drug resistance through immunomodulatory effects through microbiome regulation. We collected the patient's stool samples before FMT and 8weeks after FMT. OUTCOMES: We analyzed the microbiome composition of patients by sequencing the V3-V4 region of the 16s rRNA gene (Miseq). After FMT, the number of episodes of diarrhea and hypoalbuminemia were also corrected. The Chao 1 index after FMT, which was significantly higher than that of donors before FMT, changed to a similar level for donors after FMT. Fusobacterium nucleatum, Pyramidobacter piscolens, and Campylobacter concisus disappeared after FMT, suggesting the presence of an association between gut microbiota and CCS. LESSONS: Furthermore, we provide the possibility that microbiome modulation by FMT could serve as a complementary treatment in patients with steroid-refractory CCS.

Clinicopathologic characteristics of HER2-positive pure mucinous carcinoma of the breast.

BACKGROUND: Pure mucinous carcinoma (PMC) is a rare type of breast cancer, estimated to represent 2% of invasive breast cancer. PMC is typically positive for estrogen receptors (ER) and progesterone receptors (PR) and negative for human epidermal growth factor receptor 2 (HER2). The clinicopathologic characteristics of HER2-positive PMC have not been investigated. METHODS: Pathology archives were searched for PMC diagnosed from January 1999 to April 2018. Clinicopathologic data and microscopic findings were reviewed and compared between HER2-positive PMC and HER2-negative PMC. We also analyzed the differences in disease-free survival (DFS) and overall survival according to clinicopathologic parameters including HER2 status in overall PMC cases. RESULTS: There were 21 HER2-positive cases (4.8%) in 438 PMCs. The average tumor size of HER2-positive PMC was 32.21 mm (± 26.55). Lymph node metastasis was present in seven cases. Compared to HER2-negative PMC, HER2-positive PMC presented with a more advanced T category (p < .001), more frequent lymph node metastasis (p = .009), and a higher nuclear and histologic grade (p < .001). Microscopically, signet ring cells were frequently observed in HER2-positive PMC (p < .001), whereas a micropapillary pattern was more frequent in HER2-negative PMC (p = .012). HER2-positive PMC was more frequently negative for ER (33.3% vs. 1.2%) and PR (28.6% vs. 7.2%) than HER2-negative PMC and showed a high Ki-67 labeling index. During follow-up, distant metastasis and recurrence developed in three HER2-positive PMC patients. Multivariate analysis revealed that only HER2-positivity and lymph node status were significantly associated with DFS. CONCLUSIONS: Our results suggest that HER2-positive PMC is a more aggressive subgroup of PMC. HER2 positivity should be considered for adequate management of PMC.

Analysis of chromosome 12p over-representation and clinicopathological features in mediastinal teratomas.

Teratomas show diverse biologic behaviour and prognosis as well as variable histological features. Importantly, post-pubertal testicular teratomas composed of mature components have a potential for malignant behaviour, in contrast to ovarian dermoid cysts and pre-pubertal testicular teratomas which are considered almost always benign. On the other hand, the biological behaviour and histogenesis of extragonadal teratomas are still not fully elucidated. In this study of mediastinal mature teratoma (MT), we investigated clinicopathological features and chromosome 12 short arm (12p) status which constitutes a major genetic aberration in the germ cell tumours (GCT) and is indicative of malignant potential. A total of 123 cases of primary mediastinal MT were included, and clinical data were retrieved regarding demographic information, adjuvant treatment, post-operative clinical course, and level of serum tumour markers. Histopathological features were evaluated in 123 cases and 12p status was studied by FISH in 25 cases. Female predilection was identified in the post-pubertal group (38 males vs 77 females), and paediatric teratoma cases had longer follow-up (mean 62.2 months vs 26.5 months). All patients had excellent prognosis with no tumour-associated death, regardless of age and sex. None of the MT cases had cytological atypia and all 21 cases finally evaluated by fluorescence in situ hybridisation were negative for 12p over-representation. Our results support the benign nature of mediastinal MT and suggest the possibility that it may share a common histogenesis with pre-pubertal type GCTs.

The Prognostic Impact of Synchronous Ipsilateral Multiple Breast Cancer: Survival Outcomes according to the Eighth American Joint Committee on Cancer Staging and Molecular Subtype.

BACKGROUND: In the current American Joint Committee on Cancer staging system of breast cancer, only tumor size determines T-category regardless of whether the tumor is single or multiple. This study evaluated if tumor multiplicity has prognostic value and can be used to subclassify breast cancer. METHODS: We included 5,758 patients with invasive breast cancer who underwent surgery at Samsung Medical Center, Seoul, Korea, from 1995 to 2012. RESULTS: Patients were divided into two groups according to multiplicity (single, n = 4,744; multiple, n = 1,014). Statistically significant differences in lymph node involvement and lymphatic invasion were found between the two groups (p < .001). Patients with multiple masses tended to have luminal A molecular subtype (p < .001). On Kaplan-Meier survival analysis, patients with multiple masses had significantly poorer disease-free survival (DFS) (p = .016). The prognostic significance of multiplicity was seen in patients with anatomic staging group I and prognostic staging group IA (p = .019 and p = .032, respectively). When targeting patients with T1-2 N0 M0, hormone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative cancer, Kaplan-Meier survival analysis also revealed significantly reduced DFS with multiple cancer (p = .031). The multivariate analysis indicated that multiplicity was independently correlated with worse DFS (hazard ratio, 1.23; 95% confidence interval, 1.03 to 1.47; p = .025). The results of this study indicate that tumor multiplicity is frequently found in luminal A subtype, is associated with frequent lymph node metastasis, and is correlated with worse DFS. CONCLUSIONS: Tumor multiplicity has prognostic value and could be used to subclassify invasive breast cancer at early stages. Adjuvant chemotherapy would be necessary for multiple masses of T1-2 N0 M0, hormone-receptor-positive, and HER2-negative cancer.

Pathologically Confirmed Cerebral Amyloid Angiopathy with No Radiological Sign in a Patient with Early Onset Alzheimer's Disease.

Cerebral amyloid angiopathy (CAA) is associated with perivascular disruption, which is caused by progressive amyloid-beta (Aß) deposition in vessels. Previous autopsy studies have shown that the prevalence of CAA in Alzheimer's disease (AD) is 70% to 90%. CAA is principally characterized by restricted lobar microbleeds (MBs), which can be detected by gradient-echo T2* (GRE) and susceptibility-weighted imaging (SWI). We herein report on a 62-year-old man who presented with 8 years of memory impairment. The apolipoprotein E (APOE) genotype was ε4/ε4, and a brain GRE performed 28 months before death revealed mild atrophy and no MBs. At autopsy, the patient scored "A3, B3, C3" according to the National Institute on Aging-Alzheimer's Association guidelines; the patient thus exhibited a high level of AD neuropathological changes. Furthermore, immunohistochemical staining for Aß showed antibody accumulation and severe cerebral amyloid angiopathic changes in numerous vessels with amyloid deposits. Our case suggests that radiological CAA markers, such as cerebral microbleed (CMB) or cerebral superficial siderosis, may not suffice to detect amyloid angiopathy in cerebral vessels. CAA should therefore be considered as a combined pathology in APOE ε4 homozygotes with AD, even if such patients do not exhibit CMB on MRI.

PIK3CA Mutations and Neoadjuvant Therapy Outcome in Patients with Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: A Sequential Analysis.

PURPOSE: PIK3CA mutation is considered to be a possible cause for resistance to neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the association between PIK3CA mutations and the outcome of NAC in HER2-positive breast cancers. METHODS: A total of 100 HER2-positive breast cancer patients who had undergone NAC and surgery between 2004 and 2016 were examined. Mutation status was sequentially assessed in pre-NAC, post-NAC, and recurrent specimens taken from these patients. RESULTS: PIK3CA mutations were identified in the sequential specimens of 17 patients (17.0%). These 17 patients experienced shorter disease-free survival (DFS) than the rest of the patients (58.3 months vs. 119.3 months, p=0.020); however, there was no significant difference in pathologic complete response (pCR) and overall survival (OS) (pCR, 17.6% vs. 33.7%, p=0.191; OS, 84.5 months vs. 118.0 months, p=0.984). While there was no difference in pCR between the wild-type and mutant PIK3CA groups in pre-NAC specimens (25.0% vs. 31.8%, p=0.199), PIK3CA mutations correlated with lower pCR in post-NAC specimens (0.0% vs. 24.3%, p<0.001). Multivariate analysis revealed significantly worse DFS in the mutant PIK3CA group than in the wild-type group (hazard ratio, 3.540; 95% confidence interval, 1.001-12.589; p=0.050). Moreover, the DFS curves of the change of PIK3CA mutation status in sequential specimens were significantly different (p=0.016). CONCLUSION: PIK3CA mutation in HER2-positive breast cancer was correlated with a lower pCR rate and shorter DFS. These results suggest that PIK3CA mutation is a prognostic marker for NAC in HER2-positive breast cancer, especially in post-NAC specimens.