Background Intracholecystic papillary neoplasm (ICPN) of the gallbladder is a rare tumor and a relatively new concept. Therefore, the natural history and imaging characteristics of ICPN have not yet been fully documented. Moreover, cases who underwent curative resection for remnant gallbladder cancer, including ICPN with associated invasive carcinoma, have been rarely reported. We report a resected case of ICPN of the remnant gallbladder with associated invasive carcinoma for which we could observe a temporal change in imaging findings until malignant transformation. Case presentation A 79-year-old female patient with a surgical history of subtotal cholecystectomy for acute cholecystitis was an ambulatory patient of our institution because of postoperative surveillance for colon cancer. Ultrasonography and computed tomography incidentally detected a small nodule in the cystic remnant gallbladder. The nodule had increased in size 3 months later; thus, additional investigations were performed. Magnetic resonance imaging revealed a 10-mm enhanced nodule without evidence of extraluminal invasion. Diffusion-weighted magnetic resonance imaging revealed restricted diffusion of the lesion, and positron emission tomography revealed marked accumulation in the lesion. The lesion was diagnosed as suspicious for a malignant remnant gallbladder tumor. Therefore, remnant cholecystectomy with gallbladder bed resection was performed. Because preoperative endoscopic retrograde cholangiography revealed a relatively long intact cystic duct, extrahepatic bile duct resection was planned to be omitted. Intraoperatively, the hepatic and duodenal side bile duct where the cystic duct diverged was taped. Using these tapes, which permitted pulling the bile duct, the cystic duct located behind the bile duct could be safely exposed. The lesion was pathologically diagnosed as biliary morphologic ICPN with associated invasive carcinoma. Conclusions Because remnant cholecystectomy is an uncommon procedure and technically difficult, accurate preoperative investigation and surgical planning are important to prevent bile duct injury and omit extrahepatic bile duct resection. In the present case, intracystic change could be detected incidentally at an early stage because of previous remnant gallbladder producing (reconstituting) subtotal cholecystectomy and surveillance for other disease. This case suggests the existence of ICPN that can progress to invasive carcinoma during a short period.

BackgroundBiliary intraepithelial neoplasia (BilIN) is often distinguished by what it is not: the precancerous lesions are not mass-forming, are not the cause of bile duct obstruction, and are small enough (less than 5 mm long) to evade detection by the naked eye. Here, we describe an atypical case of BilIN resembling cholangiocarcinoma (CC) that was large enough to be identified by diagnostic imaging and presented with obstructive jaundice caused by a hematoma in the common bile duct (CBD).Case presentationA 64-year-old man presented to our hospital with upper abdominal pain and anorexia. Initial laboratory examinations revealed increased total bilirubin and a computed tomography (CT) scan revealed a dilated CBD. Gastroenterologists performed an endoscopic sphincterotomy (EST), which revealed that the cause of obstructive jaundice was a hematoma in the CBD. Enhanced CT scan and magnetic resonance cholangiopancreatography (MRCP) performed after the hematoma was drained showed improved dilation of the CBD and an enhanced wall thickness of bile duct measuring 25 × 10 mm at the union of the cystic and common hepatic ducts. A cholangioscope detected an elevated tumor covered by sludge in the CBD, and we performed an extrahepatic bile duct resection and cholecystectomy. The postoperative course was uneventful and the pathological examination of the resected tumor revealed that although the ulcerated lesion had inflammatory granulation tissue, it did not contain the components of invasive carcinoma. Many consecutive intraepithelial micropapillary lesions spread around the ulcerated lesion, and the epithelial cells showed an increased nucleus-to-cytoplasm ratio, nuclear hyperchromasia, and architectural atypia. The pathological diagnosis was BilIN-1 to -2. Immunohistochemical staining showed that S100P was slightly expressed and MUC5AC was positive, while MUC1 was negative and p53 was not overexpressed.ConclusionWe experienced an atypical case of BilIN mimicking CC that presented with obstructive jaundice caused by a hematoma in the CBD. Our case suggested that the occurrence of BilIN can be triggered by factors other than inflammation, and can grow to a size large enough to be detected by image analyses.

Background Granulocyte-colony stimulating factor (G-CSF)-producing tumors can cause leukocytosis despite an absence of infection. G-CSF-producing tumors have been reported in various organs such as the lung, esophagus, and stomach but rarely in the breast. We report a case of G-CSF-producing malignant phyllodes tumor of the breast. Case presentation An 84-year-old woman visited our hospital complaining of a lump in her left breast without fever and pain. Laboratory tests revealed elevated white blood cell (WBC) count and G-CSF levels. A malignant tumor of the breast was diagnosed by core needle biopsy. We performed a total mastectomy and sentinel lymph node biopsy. The tumor was identified as a G-CSF-producing malignant phyllodes tumor. Within 7 days after surgery, the patient’s WBC count and G-CSF level had decreased to normal levels. She is alive without recurrence 13 months after surgery. Conclusions We encountered a rare case of G-CSF-producing malignant phyllodes tumor of the breast. PET–CT revealed diffuse accumulation of FDG in the bone. Phyllodes tumors need to be differentiated from bone metastasis, lymphoma, and leukemia. We must be careful to not mistake this type of tumor for bone marrow metastasis.

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Background: Many analyzes on tumor microenvironment has made it clear that tumor infiltrating lymphocytes (TILs) plays an important role in treating cancers with high tumor mutation burden such as triple-negative breast cancer (TNBC). We reported that the relationship between TILs and PD-L1 expression (Oncotarget 2017) and revealed that high-TILs/positive-PD-L1 expression population in TNBC was associated with better prognosis. However, its molecular mechanism is still unclear. Meanwhile, it was well-known that activated T-cells work as antitumor lymphocytes by enhancing the apoptosis by granzyme B (GZMB) and perforin, and then production of cytokines such as INFγ. We focused on GZMB and examined the function of activated T-cells. Patients and Methods: This study included 230 patients with primary TNBC who underwent resection without neoadjuvant chemotherapy at our three hospitals between January 2004 and December 2014. The immunohistochemistry (IHC) scoring for GZMB expression on TILs was defined as 1 or 5%. PD-L1 positivity was defined as ≥ 10 Combined Positive Score (CPS) based on tumor and immune cells staining positive for PD-L1. Results: Of the 230 TNBC, GZMB on TILs was expressed as more than 1% and 5% positive in 181 (79%) and 50 (22%) tumors, respectively, and PD-L1 and CD8 on TILs was expressed as positive in 99 (43%) and 127 (55%) tumors, respectively. GZMB expression (more than 5%) was significantly correlated with PD-L1 expression (P=0.0048) and CD8 expression (P=0.0156). There was no significant difference in recurrence free survival (RFS) and overall survival (OS) regardless of CD8 or PD-L1expression level. Meanwhile, the patients with GZMB-positive tumors had a longer OS, compared to the patients with GZMB-negative tumors (P = 0.0155 in RFS and P = 0.0202 in OS) when PD-L1 expression on TILs was high, but not when it was low. Conclusion: OS was significantly longer among patients with high GZMB expressing TNBC. These results may validate the significance of GZMB as a biomarker for various immunotherapies in TNBC. Citation Format: Kimihisa Mizoguchi, Masafumi Nakamura. Granzyme B expression in tumor microenvironment as a biomarker for prognosis of triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-25-04.