Positive impact of laparoscopic hepatectomy versus open hepatectomy on body size-corrected bleeding in obese patients.

PURPOSE: Laparoscopic hepatectomy (LH) is reported to cause less bleeding than open hepatectomy (OH) in obese patients; however, there are no reports addressing this issue in terms of body size-corrected bleeding. METHODS: The subjects of this study were 31 obese and 149 non-obese patients who underwent LH and 32 obese and 245 non-obese patients who underwent OH. Bleeding corrected for body surface area (C-BL) was compared between the obese and non-obese patients who underwent each procedure. A multivariate analysis for increased C-BL was performed using the median C-BL for each procedure. RESULTS: The median C-BL tended to be higher in the obese patients than in the non-obese patients who underwent LH, but there was no significant difference (72 vs. 42 mL/m2, P = 0.050). However, it was significantly higher in the obese patients than in the non-obese patients who underwent OH (542 vs. 333 mL/m2, P = 0.002). In a multivariate analysis, for OH, sectionectomy or more (OR 3.20, P < 0.001) and a high BMI (OR 2.76, P = 0.018) were found to be independent risk factors, whereas for LH, a high BMI was not (OR 1.58, P = 0.301). CONCLUSIONS: Obesity was identified as a risk factor for increased bleeding with body size correction for OH, but the risk was reduced for LH.

Interobserver agreement of pathologic classification and grading of tumoral intraductal pre-invasive neoplasms of the bile duct.

Current WHO terminology and recent publications have classified tumoral (grossly visible) intraductal pre-invasive neoplasms of bile duct (TIDN) into three categories: intraductal papillary neoplasm of bile duct (IPNB), intraductal papillary oncocytic neoplasm (IOPN), and intraductal tubulopapillary neoplasm (ITPN). A total of 227 cases of TIDN and related lesions ≥3 mm in height were examined by 10 biliary pathologists referring to these 3 categories and two pathologic gradings: two-tiered system (low- and high-grade dysplasia) and modified types 1 and 2 subclassification. Among them, IPNB was the most frequent (183 cases), followed by IOPN (28 cases), while ITPN was rare (2 cases), and interobserver agreement in this classification was "substantial" (κ-value, 0.657). The interobserver agreement of two-tiered grading system of TIDN was "slight" (κ-value, 0.201), while that of modified types 1 and 2 subclassification was "moderate" (κ-value, 0.515), and 42 % were of type 1, and 58 % were of type 2. Type 1 TIDN showed occasional stromal invasion (6.7 %), whereas type 2 TIDN was frequently associated with stromal invasion (49.6 %) (p < 0.01). In conclusion, the classification of TIDN into three categories and modified types 1 and 2 subclassification are a practically applicable classification and grading system for TIDN.

Predictive score for identifying intrahepatic cholangiocarcinoma patients without lymph node metastasis: a basis for omitting lymph node dissection.

BACKGROUND: This study aimed to develop a predictive score for intrahepatic cholangiocarcinoma (ICC) in patients without lymph node metastasis (LNM) using preoperative factors. METHODS: A retrospective analysis of 113 ICC patients who underwent liver resection with systemic lymph node dissection between 2002 and 2021 was conducted. A multivariate logistic regression analysis was used as a predictive scoring system for node-negative patients based on the ß coefficients of preoperatively available factors. RESULTS: LNM was observed in 36 patients (31.9%). Four factors were associated with LNM: suspicion of LNM on MDCT (odds ratio [OR] 13.40, p < 0.001), low-vascularity tumor (OR 6.28, p = 0.005), CA19-9 ≥500 U/mL (OR 5.90, p = 0.010), and tumor location in the left lobe (OR 3.67, p = 0.057). The predictive scoring system was created using these factors (assigning 3 points for suspected LNM on MDCT, 2 points for CA19-9 ≥500 U/mL, 2 points for low vascularity tumor, and 1 point for tumor location in the left lobe). A score cutoff value of 4 resulted in 0.861 sensitivity and a negative predictive value of 0.922 for detecting LNM. Notably, no patients with peripheral tumors and a score of ≤3 had LNM. CONCLUSION: The developed scoring system may effectively help identify ICC patients without LNM.

A case of extensively spreading acinic cell carcinoma of the breast with microglandular features.

Acinic cell carcinoma (ACC) is an exceptionally rare type of breast carcinoma with a low-grade morphology and a favorable prognosis. It is postulated to be a type of invasive carcinoma arising in microglandular adenosis (MGA). We report a case of extensively spreading ACC of the breast with MGA-like features. Macroscopically, yellowish nodules were widely distributed throughout the right breast, up to the axilla, without mass formation. Microscopically, the tumor consisted of two distinct carcinoma components: one was multiple nodular lesions showing invasive carcinoma with fused solid nests, and the other was a widely spreading lesion exhibiting MGA-like features with uniform small single glands. Immunohistochemically, both components were negative for ER, PR, and HER2, and expressed EMA, S100 and lysozyme. The distinct morphology and molecular expression indicated ACC. The single glands in the MGA-like area lacked myoepithelial cells but were linearly surrounded by type IV collagen, a basement membrane component. This case supports the hypothesis that ACC and MGA have the same lineage and indicates that ACC is not necessarily a low-grade malignancy and can be aggressive.

Histological and immunohistochemical features and genetic alterations in the malignant progression of giant cell tumor of bone: a possible association with TP53 mutation and loss of H3K27 trimethylation.

In rare cases, giant cell tumor of bone (GCTB) can undergo primary or secondary malignant transformation to malignant giant cell tumor of bone (MGCTB), but the details of the molecular alterations are still unclear. The present study aimed to elucidate the clinicopathologic and molecular features of MGCTBs based on immunohistochemistry, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) of nine MGCTBs (five primary and four secondary). Seven (78%) of 9 MGCTBs were immunohistochemically positive for H3.3 G34W. In two (22%) patients, although GCTB components were focally or diffusely positive for H3.3 G34W, their malignant components were entirely negative for H3.3 G34W, which was associated with heterozygous loss of H3F3A by FISH. NGS on four MGCTBs revealed pathogenic mutations in TP53 (n = 3), EZH2 (n = 1) and several other genes. Immunohistochemical analysis of the nine MGCTBs confirmed the p53 nuclear accumulation (n = 5) and loss of H3K27me3 expression (n = 3) and showed that they were mutually exclusive. In addition, four (80%) of five cases of pleomorphic or epithelioid cell-predominant MGCTBs were positive for p53, while three (75%) of four cases of spindle cell-predominant MGCTBs were negative for trimethylation at lysine 27 of histone 3 (H3K27me3). The results suggested that p53 alteration and dysfunction of histone methylation as evidenced by H3K27me3 loss may play an important role in the malignant progression of GCTB, and might contribute to the phenotype-genotype correlation in MGCTB. The combined histologic, immunohistochemical and molecular information may be helpful in part for the diagnosis of challenging cases.

Pathologic patterns of invasive carcinoma associated with intraductal papillary neoplasms of bile duct (IPNB).

The pathologic features of invasive carcinoma associated with IPNB remain to be clarified. By using 82 cases of IPNB, the pathologic spectrum of associated invasive carcinoma and its correlation with their post-operative overall survival (OS) were examined. Invasive carcinoma was found in 52 cases (63 %) of IPNB and was classifiable into three patterns (patterns A, B and C). Pattern A was characterized by microscopic foci of invasive carcinoma in the fibrovascular stalks or confined to the bile duct mucosa and wall beneath the intraluminal pre-invasive neoplastic components of IPNB (23 cases) and pattern B by invasive carcinoma in the periductal connective tissue and in the adjacent organ(s) mainly near or beneath the intraluminal component(s) of IPNB (15 cases). Pattern C showed nodular invasive carcinoma considerably involving the intraluminal pre-invasive components and the bile duct mucosa and wall adjacent to the intraluminal pre-invasive components of IPNB (14 cases). Recognition of these three patterns of invasive carcinoma associated with IPNB may expand the pathologic spectrum of IPNB. IPNBs without invasive carcinoma showed a favorable post-operative-OS compared with those with invasion as a whole and those of pattern B and C, respectively, but showed a similar post-operative-OS to that of pattern A. IPNB of pattern B and C showed an unfavorable post-operative outcome, though there was no difference between pattern B and C. Understanding of the pathologic spectrum of associated invasive carcinoma may facilitate further pathological analysis of IPNB.

Pathological characterization of intracholecystic papillary neoplasm: A recently proposed preinvasive neoplasm of gallbladder.

Intracholecystic papillary neoplasm (ICPN) is a recently proposed gallbladder neoplasm. Its prevalence and pathologies remain to be clarified. A total of 38 ICPN cases (28 ICPNs identified among 1904 cholecystectomies (1.5%) and in 100 surgically resected primary gallbladder neoplasms (28%) in Fukui Prefecture Saiseikai Hospital, Japan, and other 10 ICPNs) were examined pathologically and immunohistochemically. They were composed of 21 males and 17 females with a mean age of 75 years old, and presented intraluminal growth of papillary lesions with fine fibrovascular stalks. ICPNs were relatively frequent in the fundus (n = 11) and body (n = 9). Grossly, the conglomerated sessile type (n = 30) was more frequent than the isolated polypoid type (n = 8). All cases were classified as high-grade dysplasia, and they were further divided into 22 cases presenting irregular structures and 16 cases presenting regular structures. The former showed frequent complicated lesions and stromal invasion (54.5%) compared to the latter (12.5%). Twenty-four cases showed predominantly either of four subtypes (11 gastric, 7 intestinal, 4 biliary and 2 oncocytic subtype), while the remaining14 cases showed mixture of more than two subtypes. In conclusion, ICPN presented unique preinvasive neoplasm with characteristic histopathologies. Irregular histologies and complicated lesions of ICPN were related to stromal invasion.

Mixed pleomorphic lobular and apocrine carcinoma of the breast: A case report suggesting pathogenesis.

Pleomorphic lobular carcinoma (PLC) of the breast is a variant of lobular carcinoma, characterized by loss of E-cadherin expression and high-grade morphologies. Whether the pathogenesis of PLC is in the ductal or the lobular lineage has been discussed. In this report, a case of PLC combined with apocrine carcinoma is presented. Histologically, the tumor showed two distinct carcinoma components: one was a typical apocrine carcinoma, and the other was a pleomorphic invasive lobular carcinoma. The former showed complete membranous expression of E-cadherin, whereas the latter aberrantly expressed it not on the cell membrane, but in the cytoplasm. Both components were triple-negative and strongly positive for GCDFP-15, suggesting apocrine differentiation. The intraductal component showed only a feature of apocrine ductal carcinoma in situ. This case suggests that apocrine carcinoma could be an origin of PLC.

Surgical Indication for Advanced Intrahepatic Cholangiocarcinoma According to the Optimal Preoperative Carbohydrate Antigen 19-9 Cutoff Value.

BACKGROUND: The indication of surgery in intrahepatic cholangiocarcinoma (ICC) patients with lymph node metastasis (LNM), macroscopic periductal infiltration (PI), and intrahepatic metastasis (IM) remains unclear. METHODS: Patients who underwent resection for mass-forming (MF) dominant ICC and unresected patients caused by LNM, IM, or locally advanced tumors (UR group) were enrolled. The significance of CA19-9 was investigated in advanced ICC. RESULTS: Seventy-three patients who underwent resection and 20 UR patients were analyzed. Using the minimum p value approach based on the overall survival, the optimal CA19-9 cutoff value was 300 U/mL. The OS of the patients with CA19-9 < 37 U/mL (n = 26; MST, 49.6 months) and 37-300 U/mL (n = 28; MST, 45.1 months) was comparable (P = 0.842); however, the OS of the patients with CA19-9 = 37-300 U/mL was significantly better than that with CA19-9 ≥ 300 U/mL (n = 19; MST, 15.3 months; P < 0.001). CA19-9 > 300 U/mL, MF + PI, and IM were independently associated with OS. The OS of the patients with CA19-9 < 300 U/mL who developed LNM (MST, 34.0 months), MF + PI (MST, 32.9 months), or IM (MST, 35.2 months), or who required major vascular resection (MST, 45.1 months) was better than those with CA19-9 ≥ 300 U/mL who developed LNM (MST, 8.7 months; P = 0.005), MF + PI (MST, 7.5 months; P = 0.040), or IM (MST, 8.7 months; P = 0.001), or who required major vascular resection (MST, 14.8 months; P = 0.015); their prognosis was similar with the UR group. CONCLUSIONS: Even if patients had ICC developing LNM, PI, or IM, or require major vascular resection, surgical resection can be indicated for patients with CA19-9 < 300 U/mL. However, the indications for either adjuvant therapy or resection should be carefully determined in patients with CA19-9 ≥ 300 U/mL.

Real-time virtual sonography examination and biopsy for suspicious breast lesions identified on MRI alone.

OBJECTIVES: The purpose of our study was to assess whether there is a potential additional value of real-time virtual sonography (RVS) to second-look ultrasound (US) examination and biopsy for breast lesions identified on MRI alone. METHODS: A retrospective review of the records of 70 consecutive patients (78 lesions) with breast abnormalities identified on MRI alone was performed. All suspicious enhancing lesions were subsequently evaluated with second-look US. Lesions not observed on second-look US underwent RVS. Pathological findings were confirmed by subsequent percutaneous biopsy or excision. RESULTS: Of the 78 MRI-detected lesions, second-look US correlation was made in 50 (64 %), including 22 malignant and 28 benign lesions. The remaining 28 lesions (36 %) were scheduled to undergo RVS. Four lesions were not visible on the second breast MRI. The remaining 24 lesions were RVS correlated and underwent RVS-guided biopsy; these included seven malignant and 17 benign lesions. Overall, 74 of 74 (100 %) true MRI-detected lesions were confirmed by histological results without using MRI-guided breast biopsy. The cancer rate was 29 %. CONCLUSIONS: RVS can increase the sonographic detection and biopsy rate of lesions identified on breast MRI alone. KEY POINTS: • All 74 MRI-detected lesions were confirmed without using MRI-guided biopsy. • Four lesions were not visible on second breast MRI. • RVS can increase sonographic detection of lesions identified on breast MRI alone. • RVS-guided breast biopsy can be an alternative to MRI-guided biopsy.

Clinicopathological significance of 'subtypes with stem-cell feature' in combined hepatocellular-cholangiocarcinoma.

BACKGROUNDS & AIMS: Combined hepatocellular-cholangiocarcinoma (cHC-CC), a malignant liver tumour with poor prognosis, is composed of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and diverse components with intermediate features between HCC and CC, which correspond to hepatic progenitor cells. According to the WHO classification 2010, we surveyed the prevalence and clinicopathological significance of each subtype with stem-cell features [SC subtype; typical subtype (TS), intermediate cell subtype (INT) and cholangiolocellular type (CLC)] in cHC-CC and HCC. METHODS: Sixty-two patients with cHC-CC (19 women and 43 men) and 26 patients with HCC (all men) were examined. The prevalence of each component was histologically assessed with assistance of mucin and immunohistochemical stainings. RESULTS: SC subtypes were observed in all cHC-CCs in various amount and combination. The prevalence of each SC subtype in cHC-CC was as follows: TS, 10 (16.1%); INT, 53 (83.9%) and CLC, 44 (71.0%). The proportion of INT was significantly correlated with gender (female-dominant) (P < 0.05), tumour size (P < 0.05), histological grading of HCC (P < 0.01) and inversely correlated with the degree of stromal fibrosis (P < 0.05). The proportion of CLC was significantly correlated with the degree of fibrosis (P < 0.01) and inflammation (P < 0.01), and inversely correlated with tumour size (P < 0.01) and histological grading of HCC (P < 0.05). The proportion of TS was significantly inversely correlated with the degree of inflammation (P < 0.01). Histological diversity score was significantly correlated with vascular invasion and the positivity for α-foetoprotein. CONCLUSION: The proportion of each SC subtype was significantly associated with certain clinicopathological factors, suggesting different properties of each SC subtypes.

Incidence of and risk factors for hepatocellular carcinoma in primary biliary cirrhosis: national data from Japan.

UNLABELLED: Primary biliary cirrhosis (PBC) primarily affects females and is rarely complicated by hepatocellular carcinoma (HCC). Although the HCC incidence in PBC patients is low, several characteristics and risk factors associated with its development have been reported. In this study, national data concerning the current status of carcinogenesis in PBC patients in Japan are reviewed. Using data from two national questionnaire surveys, we investigated the clinicopathological findings associated with HCC in PBC patients. According to the data of all reviewed PBC patients, the HCC incidence was 2.4% (71/2946). The HCC incidence by gender was 5.1% (19/370) in males and 2.0% (52/2576) in females, and the proportion of males was 26.7%. Prognosis was significantly poorer in the PBC patients with HCC than in those without. Multivariate analysis of risk factors associated with HCC by gender revealed histological stage at the time of PBC diagnosis as an independent risk factor associated with the development of HCC in females, but not in males. Furthermore, data from another national survey of 178 PBC patients with HCC (male/female = 49/129; proportion of males 27.5%) revealed that the duration between the diagnosis of PBC and that of HCC was significantly shorter in males than in females. In addition, histological stage at the time of HCC diagnosis was an independent risk factor for HCC in females, whereas no risk factors were identified in males. CONCLUSION: these data indicate that males are at risk of developing HCC at any histological stage of PBC. Therefore, male PBC patients in particular should be carefully screened for HCC from the early stages of PBC.

Pathologic significance of peribiliary capillary plexus in gallbladder neoplasm.

AIMS: Significance of peribiliary capillary plexus (PCP) in gallbladder neoplasms remains unclear. Aims are to characterize high-grade biliary intraepithelial neoplasm (BilIN), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN), precursors of gallbladder carcinoma, and to differentiate invasive carcinoma from pseudo-invasive lesions in gallbladder walls, referring to PCP. MATERIALS AND METHODS: High-grade BilIN (38 cases), PGA (5 cases), and ICPN (25 cases) were examined using capillary immunostaining. Non-neoplastic gallbladders were used as controls. RESULTS: In non-neoplastic gallbladders, a single layer of regularly dotted capillaries (PCP) was located beneath lining epithelia and around non-neoplastic glands (NNGs), including Rokitansky-Aschoff sinus (RAS), presenting a two-layer of lining epithelia and PCP. Intra-luminal components of all cases of high-grade BilIN and PGA and one-third of ICPNs presented a two-layer pattern. In the remaining ICPNs, capillaries were irregular and sparse in intraluminal neoplastic components presenting irregular and complicated lesions. Neoplastic glands in gallbladder walls of high-grade BilIN and ICPN were classifiable into 2 types: glands that were underlain by densely dotted capillaries and those that were not, with the latter suggestive of invasive carcinoma, while the former suggestive of non-invasive neoplasms involving NNGs intraepithelially and/or showing an expanding growth into gallbladder wall (pseudo-invasion). CONCLUSION: A two-layer pattern of lining epithelia and underlining capillaries were preserved in all cases of high-grade BilIN and PGA and one-third of ICPN cases. Presence or absence of dotted capillaries around neoplastic glands may be able to be added as a new pathologic feature to differentiate invasive carcinomas from pseudo-invasion in gallbladder wall.

Pathologic characterization of precursors and cholangiocarcinoma referring to peribiliary capillary plexus: a new pathologic approach to bile duct neoplasm.

The peribiliary capillary plexus (PCP) regularly and densely lines the basal side of the lining epithelia of normal bile ducts. To determine the pathology of the PCP in high-grade biliary intraepithelial neoplasms (BilINs) and intraductal papillary neoplasms of the bile duct (IPNBs), a precursor of cholangiocarcinoma (CCA), and CCA. Seventy-six cases of surgically resected high-grade BilIN and 83 cases of IPNB were histopathologically examined using endothelial immunostaining of PCP; all cases of high-grade BilIN and 40 cases of IPNB were associated with invasive CCA. Invasive and preinvasive neoplasms were pathologically examined referring to a two-layer pattern composed of biliary lining epithelia and underlying PCP unique to the bile duct. All high-grade BilIIN cases had an underlying single layer of capillaries, similar to PCP (PCP-like capillaries). In 43% of the 83 cases of IPNB, these capillaries were regularly distributed in almost all stalks and intervening stroma of intraluminal neoplastic components, while in the remaining 57% of IPNB, capillaries were sparsely or irregularly distributed in intraluminal components showing cribriform or solid growth patterns composed of striking atypical neoplastic epithelia. Invasive carcinomas associated with high-grade BilIN and IPNB were not lined with capillaries. The loss of PCP-like capillaries underlying high-grade BilIN and in stalks or stroma of IPNB may be involved in the malignant progression of these precursors. Immunostaining of PCP could be a new pathological tool for the evaluation of malignant progression and vascular supply in CCA and its precursors.

Clinicopathological significance of serum fractalkine in primary biliary cirrhosis.

BACKGROUND: Primary biliary cirrhosis (PBC), characterized by cholangitis and loss of intrahepatic small bile ducts, predominantly affects middle-aged females. We have reported that fractalkine expression associated with chronic inflammation is observed in the damaged bile ducts and periductal vessels of PBC patients, which is closely associated with chronic cholangitis. AIMS: We investigated the association between serum fractalkine levels and clinicopathological findings in PBC patients. METHODS: Liver biopsy specimens before ursodeoxycholic acid treatment and serum samples at the time of liver biopsy and 1 and 2 years after treatment were obtained from 68 PBC patients (M/F = 14/54). Serum fractalkine levels were measured by enzyme-linked immunosorbent assay, and their association with clinicopathological findings (liver function data, autoantibodies, cholangitis activity, hepatitis activity, fibrosis, bile duct loss, and orcein-positive granules) was analyzed. RESULTS: Serum fractalkine levels were in the range of 0.1-33.2 ng/ml (average, 3.2 ng/ml). They were increased in PBC patients with high degrees of cholangitis activity, a mild degree of hepatitis activity, fibrosis, orcein-positive granules, and early stages. In cases with high serum fractalkine levels, those who exhibited good biochemical responses to treatment mostly showed improved serum fractalkine levels after treatment. CONCLUSION: Serum fractalkine levels of PBC patients were high in cases with marked cholangitis activity at early stages. In addition, they closely correlated with the effect of therapy, indicating that fractalkine plays a role in the pathogenesis of initial cholangitis in early stage PBC and consequent chronic cholangitis. Thus, our results suggest that fractalkine is a good candidate for molecular-targeted treatment.

Rare Case of Advanced Gastric Cancer Complicated with Fibrinogen Storage Disease Treated with Chemotherapy plus Immune Checkpoint Inhibitor: A Case Report.

The administration of chemotherapy to cancer patients with organ dysfunction raises concerns regarding its safety. The safety profile of patients with organ dysfunction due to rare diseases treated with chemotherapy plus immune checkpoint inhibitor is limited. Fibrinogen storage disease (FSD) is a rare disease that causes liver dysfunction through endoplasmic reticulum stress response due to abnormal accumulation of fibrinogen in the endoplasmic reticulum of hepatocytes. Although chemotherapy plus nivolumab is recommended as a standard first-line treatment for patients with advanced gastric cancer (AGC), its safety profile for patients with FSD is rarely available. In this study, an 80-year-old male with gastric cancer with positive lavage cytology was scheduled to receive palliative chemotherapy. This case had liver dysfunction of unknown cause, and a liver biopsy was performed. Histopathological findings revealed a diagnosis of type II/III fibrinogen inclusion based on morphology and immunohistochemistry. Liver function was recovered by administering ursodeoxycholic acid. Therefore, the combination chemotherapy of S-1, oxaliplatin, with nivolumab as palliative chemotherapy was initiated. The case responded well to chemotherapy and achieved conversion surgery without worsening of liver function. We report a case of AGC with fibrinogen inclusion complication where chemotherapy was safely administered with a good outcome. The combination therapy of cytotoxic drugs and immune checkpoint inhibitors may be safely and effectively administered to such patients.

Head pleomorphic sarcoma showing murine double minute 2 amplification without a well-differentiated liposarcoma component in a pediatric patient.

BACKGROUND: Murine double minute 2 (MDM2) is an oncogene that inhibits p53, leading to decreased apoptosis. Sarcomas showing MDM2 amplification are rare among pediatric patients. CASE: A 14-year-old boy presented with pleomorphic sarcoma of the head showing MDM2 amplification without a well-differentiated liposarcoma component. Although chemotherapy was initially performed to reduce the tumor size before surgery, the tumor did not shrink. The patient underwent complete surgical resection. Microscopic examination revealed a positive surgical margin; thus, postoperative proton-beam radiotherapy was performed. 3 years after the therapy, no sign of recurrence was observed. CONCLUSION: Macroscopic surgical resection combined with adjuvant postoperative radiotherapy was effective against MDM2-amplified pleomorphic sarcoma refractory to neoadjuvant chemotherapy in a pediatric patient.

Intraepithelial involvement of non-neoplastic glands in papillary preinvasive neoplasms of the biliary tract: a potential diagnostic pitfall.

Intracholecystic papillary neoplasms of the gallbladder (ICPN) and intraductal papillary neoplasms of the bile duct (IPNB) show intramural neoplastic growths in addition to intraluminal papillary or polypoid neoplastic growth. Such intramural growths include intraepithelial involvement of non-neoplastic glands by preinvasive neoplastic epithelia (glandular involvement) as well as stromal invasive carcinoma. A total of 29 ICPN cases and 84 IPNB cases were pathologically examined for their glandular involvement. Glandular involvement was characterized by intramural neoplastic glands (1) showing cytological and phenotypical similarities to intraluminal preinvasive papillary neoplasms and (2) showing reminiscent configurations of non-neoplastic glands, such as (i) a mixture of preinvasive neoplastic epithelia and non-neoplastic epithelia within the same glands, (ii) neoplastic glands close to or within clustered non-neoplastic glands, or (iii) continuous growth of intraluminal preinvasive neoplastic glands into the walls. Such glandular involvement was found in 16 of 29 ICPN and 48 of 84 IPNB, and 15 of the former and 28 of the latter were not associated with invasive carcinoma. Non-invasive ICPN and IPNB with glandular involvement showed a favorable postoperative overall survival (OS). Glandular involvement by preinvasive neoplastic epithelia was frequently found in ICPN and IPNB. Such lesions may be diagnostic pitfalls in ICPN and IPNB referring to invasion. Glandular involvement without invasive carcinoma was not associated with an unfavorable postoperative OS in ICPN and IPNB. Recognition of glandular involvement may thus prevent overestimation of invasive carcinoma in ICPN and IPNB.