Prognostic relevance of the most predominant and least differentiated grades of gastric adenocarcinoma after curative gastrectomy.

BACKGROUND: Prognostic relevance of differentiation grade has remained controversial in gastric adenocarcinoma (GAC) after curative resection. METHODS: GAC patients who underwent curative gastrectomy were analyzed. Differentiation grade was evaluated according to either the most predominant or least differentiated component. Impacts of clinicopathologic parameters on postoperative recurrence and nodal metastasis were analyzed by the multivariate Cox regression analysis in pT1/2/3/4a and pT1b/2/3 GAC and by the logistic regression analysis in pT1b GAC, respectively. RESULTS: 154 patients with GAC, consisting of 34 pT1a (recurrence rate 0%), 45 pT1b (4.4%), 18 pT2 (22.2%), 40 pT3 (35.0%), and 17 pT4a (76.5%), were included. In pT1/2/3/4a GAC, recurrence was significantly associated with only depth of invasion (pT) and grade of venous invasion (VI), although either mode of differentiation grade was significantly associated with pT by the Spearman's rank correlation test. Next, given no recurrence in pT1a and high-grade histopathology in nearly all pT4a, pT1b/2/3 GAC was analyzed, revealing that recurrence was significantly associated with only VI grade and nodal metastasis. Finally, nodal metastasis was not found in any pT1a GAC, of which 44.1% was predominantly high-grade. In pT1b GAC, nodal metastasis was irrelevant to either mode of differentiation grade, tumor size, and ulceration status but was only associated with lymphatic invasion, suggesting that endoscopic resection of pT1 GAC with negative margin can be curative even with high-grade histopathology. CONCLUSION: Either mode of differentiation grade revealed limited prognostic relevance after curative gastrectomy. Our results may warrant a controversy over current curability evaluation of endoscopic GAC resection.

Stage IV and recurrent colorectal cancer cured following multimodal therapy: A case series.

The treatment strategies for colorectal cancer (CRC) with distant metastasis or metastatic recurrence after resection of the primary tumor are controversial. In the present study, four cases of patients with advanced CRC with distant metastasis who achieved disease-free survival (DFS) for >5 years and were deemed potentially cured were reported. Case 1 was that of a 53-year-old male patient with rectal cancer and liver metastases (pT3N2bM1, pStage IV), and case 2 was that of a 58-year-old female patient with descending colon cancer (pT3N1M1, pStage IV) who had lung metastases at surgery and postoperatively. Both patients achieved DFS for >5 years after simultaneous or staged partial hepatectomy or pneumonectomy followed by chemotherapy. Case 3 was that of a 75-year-old male patient with transverse colon cancer (pT3N1M0, pStage IIIB) and case 4 was that of a 73-year-old male patient with sigmoid colon cancer (pT3N0M0, pStage IIA). These cases developed liver metastases after resection of the primary tumour and were subsequently treated with chemotherapy before or after partial hepatectomy. DFS for >5 years was achieved. All four patients were considered cured. The data revealed that even patients with CRC and distant metastases can potentially be cured following multidisciplinary treatment. In the present case report, the factors that enabled these patients to be considered cured were discussed and the aim was to improve the treatment strategy to cure CRC with distant metastasis or recurrence.

Efficacy of Touch Imprint Cytology in Intraoperative Diagnosis of Invasive Mucinous Adenocarcinoma of the Lung: A Case Report and Literature Review.

A preoperative diagnosis of the peripheral small lung nodule is often difficult, and an intraoperative frozen section diagnosis (FSD) is performed to guide treatment strategy. However, invasive mucinous adenocarcinoma (IMA) is prone to be overlooked because of the low sample quality and weak atypia. We herein report a case of IMA, in which touch imprint cytology (TIC) revealed diagnostic efficacy. A 74-year-old male with a small, subsolid nodule in the right upper lobe underwent a thoracoscopic wedge resection. A grayish brown, 10 × 7 mm-sized nodule was observed on the cut surface. Intraoperative FSD revealed lung tissue with mild alveolar septal thickening and stromal fibrosis but without overt atypia. Meanwhile, TIC revealed mucus and a few epithelial cells with intranuclear inclusions, which pathologists evaluated as reactive. Finally, focal organizing pneumonia was tentatively diagnosed, and surgery was finished without any additional resection. However, permanent section diagnosis revealed a microinvasive mucinous adenocarcinoma. Nuclear inclusions were confirmed in tumor cells. In the intraoperative setting, TIC may be more advantageous than FSD in observing nuclear inclusions and mucus. Mucinous background and nuclear inclusion on TIC may suggest IMA even if FSD does not suggest malignancy in an intraoperative diagnosis of the peripheral small lung nodule.

An unusual cytological presentation of solid pseudopapillary neoplasm of the pancreas mimicking adenoid cystic carcinoma: a case report and literature review.

Endoscopic ultrasound-guided fine-needle aspiration has become the common procedure for the diagnosis of pancreatic mass, and cytological examination is usually the first approach. Solid pseudopapillary neoplasm (SPN) cytologically represents papillary structures of branching capillaries surrounded by discohesive neoplastic cells. However, it may present various degrees of tissue degeneration, causing diagnostic challenges. Here, we report a 21-year-old female who had a 2-cm-sized mass in the pancreas head. Cytological examination revealed clumps of small round/oval cells that represented microcystic configurations with mucus, mimicking adenoid cystic carcinoma or mucinous adenocarcinoma. Cercariform cells, nuclear grooves/folding, and cytoplasmic vacuoles were not observed. Histopathological examination revealed confluent small glandular structures containing acidic mucus. The tumor cells were positively stained for ß-catenin, CD10, and CD56, and negative for chromogranin A and E-cadherin, suggesting SPN, micropseudocystic variant. This variant has been scarcely described, but we should recognize it for accurate cytological triage of pancreatic tumors.

The Impact of Venous Invasion on the Postoperative Recurrence of pT1-3N0cM0 Gastric Cancer.

The impact of venous invasion (VI) on postoperative recurrence in pathological (p)T1-3N0 clinical (c)M0 gastric cancer (GC) remains unclear. We investigated the association of VI grade with prognosis in 94 (78 stage I and 16 stage IIA) patients. VI was graded during pathological examinations based on the number of VIs per glass slide as follows: v0, 0; v1, 1-3; v2, 4-6; and v3, ≥7. Filling-type invasion in veins with a minor axis of ≥1 mm increased VI grade by 1. Four (4.3%) patients experienced recurrence. Recurrence increased with pT (pT1, 0.0%; pT2, 11.1%; pT3, 18.8%) and VI grade (v0, 0.0%; v1, 3.7%, v2, 14.3%; and v3, 40.0%). Recurrence was significantly more frequent in pT3 than pT1 and in v2 + v3 than v0 (p = 0.006 and 0.005, respectively). Kaplan-Meier curve analyses demonstrated a significant decrease in recurrence-free survival according to pT (p = 0.0021) and VI grade (p < 0.0001). Multivariate Cox analysis revealed a significant association of VI grade with recurrence (p = 0.049). These results suggest that VI grade is a potential recurrence predictor for pT1-3N0cM0 GC. No recurrence can be expected in cases with pT1 or VI grade v0. Adjuvant therapy might be considered for pT3 or VI grade v2 + v3.

Risk stratification for predicting postoperative recurrence of gastric cancer by grade of venous invasion.

BACKGROUND: Venous invasion (VI) in pathological examination of surgically resected gastric cancer (GC) may predict postoperative recurrence, but there are no objective criteria for VI grading. METHODS: 157 GC patients (pathological stages I 82, II 34, and III 41) who underwent surgery with curative intent were analyzed. VI was graded in pathological examination by elastica van Gieson staining based on the number of VIs per glass slide as follows: v0, 0; v1, 1-3; v2, 4-6; and v3, ≥ 7. Filling-type invasion in veins with a minor axis of ≥ 1 mm increased the grade by 1. The association of VI grade with prognosis was statistically analyzed. RESULTS: Recurrence increased with VI grade (v0 1.5%, v1 29.6%, v2 41.7%, v3 78.6%). VI grade as well as pathological (p) tumor, node, metastasis (TNM) stage was a significant recurrence predictor by the multivariate Cox analysis. VI grade was implicated in hematogenous and peritoneal recurrences independent of pTNM stage but not in nodal recurrence. GC was then divided into two tiers, without indication of adjuvant chemotherapy (AC) (pStage I, pT1 and pT3N0) and with AC indication (pStages remaining II/III), based on the ACTS-GC trial, which is common in Japan and East Asia. VI grade was a significant recurrence predictor in both tiers. v2/v3 revealed a significantly worse recurrence-free survival (RFS) than v0/v1 in GC without AC indication. v0/v1 exhibited RFS rate exceeding 95% even after 5 years but that of v2/v3 fell around 70% within one year postoperatively, suggesting that AC may be considered for this tier with v2/v3. GC with AC indication exhibited dismal RFS according to the VI grade. RFS rate fell below 80% within one year postoperatively when VI was positive, while recurrence was not observed in v0, which was, however, rare in this tier (10.9%). Differentiation grade did not significantly affect postoperative prognosis in both tiers. CONCLUSIONS: VI grade was a significant predictor of postoperative GC recurrence irrespective of the AC indication based on the ACTS-GC study and this VI grading system could be applied in future studies of adjuvant therapy in GC presently deemed without AC indication in Japan.

Apparent diffusion coefficient by magnetic resonance cholangiopancreatography is useful for grading cholecystitis and surgery planning.

INTRODUCTION: Laparoscopic cholecystectomy is a standard procedure for treating cholescytitis, but severe inflammation may cause complications. Our previous study showed that the apparent diffusion coefficient (ADC) values could predict difficult surgery. In the present study, relevance of ADC values in grading the severity of cholecystitis was pathologically investigated. METHODS: We retrospectively analyzed a total of 50 patients who underwent laparoscopic cholecystectomy or laparotomic cholecystectomy/choledocholithotomy. The degree of inflammation in the neck of the gall bladder was pathologically graded into three tiers (grade 1, mild; grade 2, moderate; grade 3, severe), and ulceration, lymphoid follicle formation, and wall thickness of the gallbladder neck were recorded. All factors were statistically compared with the measured ADC values. RESULTS: The ADC value was significantly lower in the severe inflammation group ( grade 3) than in the weak inflammation group (grades 1 and 2) (1.93 ± 0.22 vs 2.38 ± 0.67, respectively; P = .02). Ulceration and wall thickness in the gallbladder neck were significantly correlated with ADC values (P = .04 and .006, respectively), and lymphoid follicle formation was marginally correlated with ADC values (P = .06). The diagnostic utility of the ADC values decreased as the interval between imaging and cholecystectomy increased. [Correction added on 19 October 2022, after first online publication: [On the first sentence of the Results section, (grades 2 and 3) for weak inflammation group has been changed to (grades 1 and 2).] CONCLUSION: ADC values were inversely associated with the pathologic intensity of cholecystitis. We recommend that the ADC value be measured before surgery, so that the procedure can be accordingly planned.

Reclassification of atypical immature metaplasia of the uterine cervix by combination of nuclear features on hematoxylin and eosin-stained sections without auxiliary immunohistochemistry.

Reclassification of endocervical atypical immature metaplasia (AIM) into reactive changes and neoplastic lesion is often challenging. We aimed to accurately reclassify AIM on hematoxylin and eosin (HE)-stained sections without auxiliary immunohistochemistry (IHC). A total of 133 AIM diagnosed by punch biopsy were reclassified by IHC for p16 and Ki-67 into high-grade squamous intraepithelial lesion (HSIL) or negative for intraepithelial lesion or malignancy or low-grade squamous intraepithelial lesion (NILM/LSIL) as a reference. Nuclear features significantly associated with HSIL on HE-stained sections were extracted by multivariate logistic regression analysis. Propensity score (PS) of HSIL was calculated in each case and cut-off was determined by receiver operation characteristic (ROC) curve analysis. As a result, AIM was reclassified into 104 NILM/LSIL and 29 HSIL by IHC. Compared with reference diagnosis, accuracy of pathologists' subjective diagnosis was 54.9% (kappa coefficient, 0.208). Three nuclear features on HE-stained sections, ie, nuclear enlargement with anisokaryosis, nuclear hyperchromasia, and mitosis, were significantly associated with HSIL. The ROC curve analyses revealed that PS and number of nuclear features were significant predictors of HSIL. Diagnostic accuracy of PS-based diagnosis was 76.7% (kappa, 0.447). When AIM with 2 or more of the 3 nuclear features was diagnosed with HSIL, diagnostic accuracy was 77.4% (kappa, 0.448). Nuclear feature-based diagnosis significantly improved diagnostic accuracy on HE-stained sections compared with subjective diagnosis and may be useful when IHC is not available. However, a considerable proportion of AIM would still remain misdiagnosed and IHC for p16 and Ki-67 should be mandatory for accurate reclassification.

Risk stratification for predicting postoperative recurrence/metastasis of colorectal cancer by grade of venous invasion coupled with histological subtype.

BACKGROUND: Colorectal cancer (CRC) consists of several histological subtypes that greatly affect prognosis. Venous invasion (VI) has been implicated in the postoperative recurrence of CRC, but the relationship between the VI grade and postoperative recurrence in each histological subtype has not been clarified thus far. METHODS: A total of 323 CRCs without distant metastasis at surgery (pathologic stage III or lower), including 152 well-to-moderately differentiated adenocarcinomas (WMDAs), 98 poorly differentiated adenocarcinomas (PDAs), and 64 mucinous adenocarcinomas (MUAs), were analyzed. They were routinely processed pathologically, and VI was graded as follows irrespective of location by elastica van Gieson staining: v0 (none), no venous invasion; v1 (mild), 1-3 invasions per glass slide; v2 (moderate), 4-6 invasions per glass slide; and v3 (severe), ≥ 7 invasions per glass slide. Filling-type invasion in veins with a minor axis of ≥ 1 mm increased the grade by 1. The association of VI grade with prognosis was statistically analyzed. RESULTS: All recurrences occurred as distant metastases. Recurrence increased with VI grade in WMDA (v0 11.8%, v1 15.8%, v2 73.9%, v3 75.0%) and MUA (v0 15.2%, v1 30.8%, v2 40.0%). The recurrence rate was relatively high in PDA even with v0 and increased with VI grade (v0 27.8%, v1 32.7%, v2 33.3%, v3 60.0%). VI grade was a significant predictor of recurrence in WMDA but not in PDA and MUA by multivariate analysis. In node-negative (stage II or lower) CRC, the recurrence-free survival (RFS) rate exceeded 90% in v0 and v1 WMDA until postoperative day (POD) 2100 and v0 MUA until POD 1600 but fell below 80% in the other settings by POD 1000. In node-positive (stage III) CRC, the RFS rate fell below 80% in all histological subtypes by POD 1000. CONCLUSIONS: VI grade v1 had a similar recurrence rate and RFS as grade v0 and may not warrant adjuvant chemotherapy in node-negative (stage II or lower) WMDA. In addition to node-positive (stage III) CRC, adjuvant chemotherapy may be indicated for node-negative (stage II or lower) CRC when it is WMDA with VI grade v2 or v3, MUA with VI, or PDA.

Histopathological Analysis of Decellularized Porcine Small Intestinal Submucosa after Treatment of Skin Ulcer.

BACKGROUND: Decellularized porcine small intestinal submucosa (SIS), commercialized as an extracellular matrix rich in cell-inducing substrates and factors, has been clinically applied to treat intractable skin ulcers and has shown therapeutic effects. The SIS reportedly induces cell infiltration and integrates with the ulcer bed after 3-7 days of application. The attached SIS degenerates over time, and the remaining mass appears as slough, below which is granulation tissue that is essential for healing. This study aimed to determine whether the slough should be removed in clinical settings. METHODS: Five patients with intractable skin ulcers were included in this case series. Seven days after applying a two-layer fenestrated-type SIS to the ulcer, the removed slough was histopathologically examined. RESULTS: The collagen fibers of the SIS somewhat degenerated, and inflammatory cell infiltration was observed from the ulcer side to the surface side of the SIS. Neovascularization was similarly observed on the ulcer side. The degree of inflammatory cell infiltration decreased from the ulcer side to the surface side, whereas pus (ie, aggregates of neutrophils) was observed on the surface and ulcer edges. Additionally, the removed slough contained regenerative epithelium on the ulcer side of the remaining collagen fibers. CONCLUSIONS: After treating intractable skin ulcers using SIS, we recommend removal of the upper surface and ulcer edge of the degenerated SIS or slough to prevent infection and preservation of the lower side of the degenerated SIS to maintain the granulation tissue and regenerative epithelium.

Effect and limitation of neoadjuvant chemotherapy for pancreatic ductal adenocarcinoma: consideration from a new perspective.

BACKGROUND: Effect of neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC) has remained under investigation. We investigated its effect from a unique perspective and discussed its application. PATIENTS AND METHODS: We retrospecively analyzed consecutive 131 PDAC patients who underwent pancreatoduodenectomy and distal pancreatectomy. Clinicopathologic data at surgery and postoperative prognosis were compared between patients who underwent upfront surgery (UFS) (n = 64) and those who received NAC (n = 67), of which 62 (92.5%) received gemcitabine plus S-1 (GS). The GS regimen resulted in about 15% of partial response and 85% of stable disease in a previous study which analyzed a subset of this study subjects. RESULTS: Tumor size was marginally smaller, degree of nodal metastasis and rate of distant metastasis were significantly lower, and pathologic stage was significantly lower in the NAC group than in the UFS group. In contrast, significant differences were not observed in histopathologic features such as vessel and perineural invasions and differentiation grade. Notably, disease-free and overall survivals were similar between the two groups adjusted for the pathologic stage, suggesting that effects of NAC, including macroscopically undetectable ones such as control of micro-metastasis and devitalizing tumor cells, may not be remarkable in the majority of PDAC, at least with respect to the GS regimen. CONCLUSIONS: NAC may be useful in downstaging and improving prognosis in a small subset of tumors. However, postoperative prognosis may be determined at the pathologic stage of resected specimen with or without NAC. Therefore, NAC may be applicable to borderline resectable and locally advanced PDAC for enabling surgical resection, but UFS would be desirable for primary resectable PDAC.

Clinical impacts of resection margin status and clinicopathologic parameters on pancreatic ductal adenocarcinoma.

BACKGROUND: The clinical relevance of pancreatic intraepithelial neoplasia (PanIN) at the resection margin of pancreatic ductal adenocarcinoma remains unknown. We aimed to investigate its clinical impact at the pancreatic transection margin (PTM) and, based on the result, determine the prognostic values of the resection margin status and other clinicopathologic parameters. PATIENTS AND METHODS: We retrospectively analyzed 122 consecutive patients who underwent pancreatoduodenectomy or distal pancreatectomy between 2006 and 2018. Pathologic slides were reviewed and survival data were retrieved from institutional databases. Associations between two variables were investigated by Fisher's exact test. Survival curves were generated by the Kaplan-Meier method. Prognostic factors were assessed using Cox regression analysis. RESULTS: Tumors were resected without leaving macroscopic remnants. The median follow-up period after surgery was 524.5 days. Cancer-related death (n = 72) was marginally and significantly associated with local recurrence (n = 22) and distant metastasis (n = 79), respectively. Local recurrence and distant metastasis occurred independently. After excluding cases with invasive cancer at any other margin, PanIN-2 or PanIN-3 (n = 21) at the PTM did not adversely affect prognoses compared with normal mucosa or PanIN-1 (n = 57) with statistical significance. R0 resection (n = 78), which is invasive cancer-free at all resection margins, showed somewhat better local recurrence-free and overall survivals as compared with R1 resection (n = 44), which involves invasive cancer at any resection margin, but the differences did not reach statistical significance. In contrast, differentiation grade and nodal metastasis were significant predictors of distant metastasis, and tumor location and differentiation grade were significant predictors of cancer-related death. Although there was no significant difference in differentiation grade between the head cancer and the body or tail cancer, nodal metastasis was significantly more frequent in the former than in the latter. CONCLUSIONS: PanINs at the PTM did not adversely affect prognosis and R0 resection was not found to be a significant prognostic factor. Differentiation grade might be an indicator of occult metastasis and affect patients' overall survival through distant metastasis. In addition to successful surgical procedures, tumor biology may be even more important as a predictor of postoperative prognosis.

Relationship between endoscopic mucosal healing and histologic inflammation during remission maintenance phase in ulcerative colitis: a retrospective study.

Background and study aims Recently, histological inflammation has been suggested to be an important predictor of sustained remission or relapse of ulcerative colitis (UC). In this study, we retrospectively compared severity of histological inflammation with endoscopic findings in UC patients with mucosal healing (MH) in the remission maintenance phase, and investigated whether histological healing could be a predictor of sustained remission. Patients and methods This study included 166 patients with MH in the remission maintenance phase. Endoscopic evaluation was based on the Mayo endoscopic subscore (MES), and MH was defined as MES 0 or 1. Severity of histological inflammation was graded according to the Matts classification. Patients with Matts 1 and 2 were included in the histological healing (HH) group, and those with Matts 3, 4, and 5, in the non-histological healing (NHH) group. In patients with MH, incidence of relapse was compared and analyzed according to severity of histological inflammation. Results The remission maintenance rate was significantly higher in the MES 0 group than in the MES 1 group ( P  = 0.004). The rate was significantly higher in the HH group than in the NHH group ( P  = 0.003). Within the MES 1 group, the rate was significantly higher in the HH subgroup than in the NHH subgroup ( P  = 0.030). Conclusions This retrospective study suggests that histological healing can be a predictor of sustained remission in UC patients, and examination of histological inflammation provides useful information for long-term management of UC, particularly in patients with MES 1.

Sex steroid hormone receptors in bladder cancer: Usefulness in differential diagnosis and implications in histogenesis of bladder cancer.

OBJECTIVE: In rare cases, differential diagnosis between bladder cancer (BC) and gynecological tract cancer (GTC) is difficult because of anatomical proximity and morphological similarity. We analyzed expression status of sex steroid hormone receptors in BC in this study. First, we investigated their usefulness as a histological marker for differential diagnosis. Second, we considered their roles in BC histogenesis. METHODS: Estrogen receptor α (ERα) and progesterone receptor (PgR) expression was investigated by immunohistochemistry in 125 BCs obtained by transurethral resection or biopsy, then in nonneoplastic background mucosa (trigone, fundus, and dome) of 33 total cystectomy samples. They were evaluated as positive when ≥ 1% of 500 subject cells were immunoreactive with moderate or strong intensities. RESULTS: ERα and PgR were positive in 38.4% and 3.2% of BCs, respectively, suggesting that ERα status alone could not definitely differentiate between BC and GTC. ERα expression was not significantly associated with age and sex of BC patients and histopathology of BCs. Although not significant, ERα expression was more frequent in higher grade (G1/G2 vs. G3/G4; P = 0.143) and marginally associated with advanced stage of BCs (pTis/pTa/pT1 vs. pT2/pT3, P = 0.056). ERα expression was significantly more frequent in background mucosa with ERα-positive BC (In the epithelium and stroma; both P < 0.001). ERα expression was continuously observed from normal to malignant epithelium in some cases. Although not significant, Brunn's nest or cystitis glandularis was more frequent in background mucosa with ERα-positive BC (P = 0.218). Analyses of nonneoplastic mucosa in cystectomy revealed that ERα was more frequently positive in urothelium of trigone, a predilection site for cystitis glandularis, than those of fundus and dome, with a significant difference between trigone and dome (P = 0.034). These data suggest that chronic inflammation may up-regulate ERα in the background epithelium, especially in trigone, and ERα expression in BC might be the reflection of bladder epithelium from which BC arose. CONCLUSIONS: Usefulness of ERα was limited in differential diagnosis between BC and GTC. ERα up-regulation might not play a critical role in the development of BC because it was already noted in the background bladder mucosa.

Impact of Tumor Location on Postoperative Outcome of Intraductal Papillary Neoplasm of the Bile Duct.

BACKGROUND: The concept of intraductal papillary neoplasm of the bile duct (IPNB) has been proposed to be the biliary equivalent of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. While the classification of IPMNs is based on their location of duct involvement, such classification has not been fully evaluated for IPNBs. The aim of this study is to investigate the value of IPNB classification based on its location. METHODS: A total of 306 consecutive patients who underwent surgical resection with a diagnosis of bile duct tumor were enrolled. Among these patients, 21 were diagnosed as having IPNB. The IPNBs were classified into two groups as follows: extrahepatic IPNB, which located in the distal or perihilar bile duct, and intrahepatic IPNB, which located more peripherally than the hilar bile duct. The clinicopathological features of the two groups were then compared. RESULTS: Extrahepatic IPNB tended to show more invasive characteristics than intrahepatic IPNB (presence of invasive component: 40.0 vs. 9.1%, p = 0.084). Moreover, patients with extrahepatic IPNB showed significantly poorer relapse-free survival (RFS) than those with intrahepatic IPNB [5-year RFS rate (%): 81.8 vs. 16.2, p = 0.014]. CONCLUSION: Patients with intrahepatic IPNB show more favorable pathological characteristics and postoperative survival outcomes than those with extrahepatic IPNB.

Oestrogen receptor-negative/progesterone receptor-positive phenotype of invasive breast carcinoma in Japan: re-evaluated using immunohistochemical staining.

BACKGROUND: The existence of progesterone receptor (PgR) expression in oestrogen receptor (ER)-negative breast carcinoma is controversial. Here, we re-evaluated ER-negative/PgR-positive (ER-/PgR+) carcinoma cases by immunohistochemical staining (IHC). MATERIALS AND METHODS: We selected patients who underwent surgery for primary breast carcinoma from our databases at Dokkyo Medical University Hospital and Kameda General Hospital. Among the 9844 patients, the largest series in Japan, 27 (0.3%) were initially diagnosed as ER-/PgR+ breast carcinomas and we re-evaluated by IHC. RESULTS: The re-evaluated IHC showed that of the 27 patients with the initial results of ER-/PgR+, 12 were ER+/PgR+, 8 were ER-/PgR-, and 7 were ER-/PgR+. ER was negative in 12 of 27 patients (44.4%), and PgR was positive in 8 of 27 patients (29.6%). In our seven re-evaluated and confirmed as ER-/PgR+ cases, the staining proportions of tumor cells were 0% in ER and 1-69% (average 15.8%) in PgR. The average staining proportion of PgR in the re-evaluated ER-/PgR+ phenotype was lower than the initial diagnosis. Histological grading was as follows: grade I, one case; grade II, two cases; grade III, four cases. There were two lymph-node-positive cases. CONCLUSIONS: The ER-/PgR+ phenotype was confirmed after re-evaluation of ER and PgR assessment by a different pathologist. We recommend that pathologists discuss with clinicians, or re-test and re-evaluate ER/PgR expression, particularly in low-grade carcinoma and with a high staining proportion of PgR in the ER-/PgR+ phenotype.

Nuclear Morphometry of Lung Squamous Cell Carcinomas in Cytologic Study.

BACKGROUND: The nuclei of most cancer cells in histopathologic preparations differ from normal nuclei and vary individually in size, shape, and chromatin pattern. Although the cytologic characteristics of squamous cell carcinoma (SCC) of the lung have been described, quantification of the cytologic features has not been established. METHODS: Cytologic investigations were performed on bronchial brushings or washings, or fine-needle aspirates. We analyzed the nuclear area (NA) of 50 tumor cells in 32 patients with SCC of the lung and 50 bronchial epithelial cells in 20 patients with no evidence of malignancy including inflammatory lesions. RESULTS: The NA of tumor cells (102.4 ± 26.2 µm2) was significantly larger than that of bronchial epithelial cells (64.1 ± 16.9 µm2) (P = 0.001). The receiver operating characteristic (ROC) curve analysis showed that an NA cutoff level of 86 µm2 had a sensitivity of 75% and specificity of 88% to detect malignant components. CONCLUSION: We conducted quantitative analyses of NA in SCC using cytologic specimen, NA was a useful parameter for evaluation of differential diagnosis between SCC and non-malignancies even in cytologic specimens.

Characteristic Histological Findings of Asymptomatic EBV-associated Lymphoproliferative Disorders in Tonsils.

Recently, an in situ hybridization (ISH) and immunohistochemical study demonstrated that Epstein-Barr virus (EBV) infection may be involved in tonsillar hypertrophy and recurrent tonsillitis in children and young adolescents. The present study was based on 630 consecutive specimens from tonsillectomies performed at the Dokkyo University School of Medicine between 2002 and May 2017. Clinical findings were obtained from hospital records. Histologically, a "pale clear zone" was characterized by hyperplastic germinal centers with ill-defined borders and interfollicular expansion. Immunohistologically, the majority of immunoblasts were CD20-positive, whereas medium to large lymphoid cells usually expressed CD3. Among 14 lesions, numerous EBV-encoded small RNA (EBER)-positive cells were detected in 10. In 7 of these 10 lesions, EBER-positive cells were detected in germinal centers as well as in the interfollicular area. Based on our results, the "pale clear zone" suggests asymptomatic EBV infection of the tonsil. The present study demonstrated that "pale clear zones" should be taken into consideration when diagnosing asymptomatic EBV-associated LPDs in the tonsils of children and young adolescents as well as in middle-aged patients.

Intraoperative frozen section diagnosis of bile duct margin for extrahepatic cholangiocarcinoma.

AIM: To evaluate the usefulness of frozen section diagnosis (FSD) of bile duct margins during surgery for extrahepatic cholangiocarcinoma (CCA). METHODS: We retrospectively analyzed 74 consecutive patients who underwent surgery for extrahepatic CCA from 2012 to 2017, during which FSD of bile duct margins was performed. They consisted of 40 distant and 34 perihilar CCAs (45 and 55 bile duct margins, respectively). The diagnosis was classified into three categories: negative, borderline (biliary intraepithelial neoplasia-1 and 2, and indefinite for neoplasia), or positive. FSD in the epithelial layer, subepithelial layer, and total layer was compared with corresponding permanent section diagnosis (PSD) postoperatively. Then, association between FSD and local recurrence was analyzed with special reference to borderline. RESULTS: Analysis of 100 duct margins revealed that concordance rate between FSD and PSD was 68.0% in the total layer, 69.0% in the epithelial layer, and 98.0% in the subepithelial layer. The extent of remaining biliary epithelium was comparable between FSD and PSD, and more than half of the margins lost > 50% of the entire epithelium, suggesting low quality of the samples. In FSD, the rate of negative margins decreased and that of borderline and positive margins increased according to the extent of the remaining epithelium. Diagnostic discordance between FSD and PSD was observed in 31 epithelial layers and two subepithelial layers. Alteration from borderline to negative was the most frequent (20 of the 31 epithelial layers). Patients with positive margin in the total and epithelial layers by FSD demonstrated a significantly worse local recurrence-free survival (RFS) compared with patients with borderline and negative margins, which revealed comparable local RFS. Patients with borderline and negative margins in the epithelial layer by PSD also revealed comparable local RFS. These results suggested that epithelial borderline might be regarded substantially as negative. When classifying the status of the epithelial layer either as negative or positive, concordance rates between FSD and PSD in the total, epithelial, and subepithelial layers were 95.0%, 93.0%, and 98.0%, respectively. CONCLUSION: During intraoperative assessment of bile duct margin, borderline in the epithelial layer can be substantially regarded as negative, under which condition FSD is comparable to PSD.

Gastric Adenocarcinoma of the Fundic Gland Type after Endoscopic Therapy for Metachronous Gastric Cancer.

A 78-year-old man underwent endoscopic submucosal dissection (ESD) for early gastric adenocarcinoma twice in 2009 and 2014. Between the procedures, he successfully completed Helicobacter pylori eradication therapy. In May 2015, upper endoscopy screening showed two elevated lesions on the gastric fundus, and en bloc resection by ESD was performed. We histopathologically diagnosed the patient to have gastric adenocarcinoma of the fundic gland type. In this case, the two lesions of gastric adenocarcinoma of the fundic gland type multifocally developed after ESD for metachronous gastric tubular adenocarcinoma. Furthermore, they appeared in the gastric fundus, where atrophy had been improved due to eradication therapy.