Cell Block-Based Two-Dimensional and Immunocytochemical Analyses Could Reduce Atypical/Indeterminate Case Frequency in Breast Fine-Needle Aspiration Cytology: A Retrospective Analysis.

INTRODUCTION: In fine-needle aspiration of the breast (FNAB), the "atypical" category encompasses both benign and malignant lesions, particularly papillary proliferative lesions, as per the latest WHO classification. We aimed to reduce atypical cases and improve diagnostic accuracy by investigating the utility of cell block (CB) analysis. METHODS: FNAB CB samples (2018-2022) were reviewed using smear only or CBs. CB-based diagnosis was performed with 2D morphological analysis and immunocytochemistry using ER, CK5/6, p63, SMA, and CD56. Samples were reclassified as "benign," "atypical," "suspicious of malignancy," "malignant," or "insufficient/inadequate." Atypical cases were reexamined. Diagnoses were validated histologically. RESULTS: On examining the FNAB samples (n = 149; 32 atypical), 2D CB sectioning achieved a clearer definition of myoepithelial cells and fibrovascular cores than Papanicolaou staining. Immunocytochemistry was evaluated for 36 cases: estrogen receptor (ER)- and CK5/6+ tumors were reclassified as benign; ER+ and CK5/6- tumors as malignant; p63- tumors as invasive; papillary malignant tumors with a smooth muscle actin (SMA)+ fibrovascular core and p63- myoepithelial cells as encapsulated papillary carcinoma; and CD56+ carcinomas as neuroendocrine carcinoma. Diagnostic rates were as follows: benign (44% FNAB, 51% CB), atypical (21% FNAB, 3% CB), suspicious of malignancy and malignant (28% FNAB, 40% CB), and insufficient/inadequate (7% FNAB, 6% CB). CB achieved >85% sensitivity, specificity, and positive and negative predictive values. CONCLUSION: CBs represent 3D FNA cell morphology using 2D sections, enabling adaption of pathology criteria to the cytological material. Immunocytochemical staining of CBs can predict low nuclear grade papillary tumors and reduce atypical case frequency, improving diagnostic accuracy.

[A Successful Management of Thrombocytopenia Due to Multiple Lung Metastasis of Intrahepatic Cholangiocarcinoma Using Laparoscopic Splenectomy-A Case Report].

We report a case of multiple lung metastasis of intrahepatic cholangiocarcinoma treated with chemotherapy, in which laparoscopic splenectomy was effective for thrombocytopenia. A 74-year-old woman was diagnosed with multiple lung metastasis of intrahepatic cholangiocarcinoma 6 years after partial liver resection(S3). She was undergoing treatment for post-transfusion hepatitis C infection since the age of 46 years and developed thrombocytopenia due to splenomegaly. The previous hospital determined that there was no indication for chemotherapy due to thrombocytopenia. Elective laparoscopic splenectomy resulted in an increase in the platelet count and facilitated the initiation of gemcitabine(GEM)and cisplatin (CDDP)combination chemotherapy. The patient has maintained a good treatment course without interruption due to thrombocytopenia during chemotherapy. In advanced cancer patients with thrombocytopenia complication due to splenomegaly, laparoscopic splenectomy may offer an effective auxiliary means for the safe implementation of chemotherapy.

Comparative evaluation of nuclear and histological grades as prognostic factors for invasive breast cancer.

BACKGROUND: Although tumor grade, defined by either the nuclear grade (NG) or the histological grade (HG), is widely accepted as one of the prognostic factors for breast cancer, there is a limited direct comparison between these two grading systems. The object of the current study was to compare their prognostic capabilities on the same specimen in a single institutional cohort. METHODS: We collected data from 1125 patients with breast cancer who underwent surgery at Kaizuka City Hospital between 2002 and 2016 and analyzed the prognostic capability of NG and HG in comparison with other clinicopathological factors. Pathological diagnoses were performed by a single pathologist throughout the study period. RESULTS: The median follow-up was 52.9 months. During the follow-up period, 103 distant recurrences were observed. The concordance rate of grades between NG and HG was 72.1%. The 5-year recurrence-free survival (RFS) rates for patients with NG1, NG2, and NG3 were 90.6%, 91.8%, and 82.2%, respectively, and the rates for patients with HG1, HG2, and HG3 were 92.7%, 88.6%, and 82.5%, respectively. Significant differences in RFS were noted among each grade for HG. However, this was not true for NG; a significant difference was not noted between NG1 and NG2. In terms of subtypes, both NG3 and HG3 were significantly associated with worse outcomes in patients with ER-positive/HER2-negative tumors. CONCLUSIONS: Although not a few patients exhibited discordant results between NG and HG, both NG and HG predict outcomes for breast cancer patients, but the latter might appear to be superior as a three-grade classification scale.

Fine-needle aspiration cytology for the diagnosis of solid basaloid adenoid cystic carcinoma of the breast: Its role, limitation, and perspective.

Solid basaloid adenoid cystic carcinoma (SB-AdCC) is a subtype of breast AdCC which shows more aggressive clinical behavior than other subtypes. Fine-needle aspiration (FNA) cytology is a useful diagnostic tool for breast malignancies. However, most of the diagnostic cytological characteristics of AdCC are not present in SB-AdCC and cytomorphological studies of this subtype are limited. Here, we evaluated the utility of FNA in the diagnosis of SB-AdCC of the breast. A search of the pathology archives of our institutions for FNA specimens of histologically confirmed SB-AdCC between 2012 and 2019 identified four patients with SB-AdCC of the breast. All patients were female and the average age was 60 years. Cytologically, one case was classified as malignant, two as indeterminate, and one as unsatisfactory. Smears had low to moderate cellularity. All smears showed ribbon-like material surrounding the clusters and a vertical nuclear arrangement toward the peripheral rim. Hyaline globules appeared only in one case. Cells in all cases showed an oval, angular, and spindle shape hyperchromatic nuclei with mild to severe atypia, and also dispersed naked nuclei similar to the cells of the clusters were detected in one case. In histological sections, these cytological findings were compatible with the histological findings and divergent histological differentiation was detected. Diagnosing of few cellular smears of SB-AdCC is difficult whereas the features of peripheral rim of the clusters, naked nuclei, and the divergent differentiation may be important for diagnosing SB-AdCC of the breast.

Atypical pseudoangiomatous stromal hyperplasia showing rapid growth of the breast: Report of a case.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign lesion manifesting as myofibroblastic proliferation and anastomosing slit-like spaces. Atypical PASH is an extremely rare lesion characterized by cytological alteration of myofibroblast, presenting as myofibroblastic sarcoma arising from PASH. To our knowledge, only one other case has been reported since the first report of Rosen. We present a case of atypical PASH. A 39-year-old female presented with a round, elastic hard, painless mass in the left breast. Mammography and ultrasonography revealed no definitive sign of malignancy. Core needle biopsy report was suggestive of atypical PASH. Five months later, the mass had grown rapidly with pain. Considering the clinicopathological features, excision was performed. Pathological examination revealed the spindle cells proliferation in collagenous stroma. The spindle cell involved the adipose tissue and lobules and lined peudoangiomatous spaces. These cells exhibited marked cytological atypia and mitotic activity. Immunohistochemically, these spindle cells were positive for SMA, CD10, and bcl-2, and negative for podoplanin, p63, CD31, ERG and cytokeratins. The final diagnosis was atypical PASH. She is tumor-free on 12 months follow-up. The nature of atypical PASH remains unknown. Further studies are required for a clear definition, a new histological entity and diagnostic criteria.

[A Case of Liver Metastasis of Intrahepatic Cholangiocarcinoma That Achieved Clinical Complete Response after Gemcitabine and Cisplatin Combination Chemotherapy].

We report a case of liver metastasis of intrahepatic cholangiocarcinoma that achieved clinical complete response after gemcitabine(GEM)and cisplatin(CDDP)combination chemotherapy. The patient was a 69-year-old man who was diagnosed with intrahepatic cholangiocarcinoma with hilar invasion and intrahepatic metastasis(cT4N0M0, Stage ⅣA)and was initially treated with right trisegmentectomy with left portal vein resection, lymph node dissection, and reconstruction of the left portal vein and biliary tract after transhepatic portal vein embolization(PTPE). S-1 was administered continuously as postoperative adjuvant chemotherapy, and the patient showed no signs of recurrence. Three years after the surgery, a CT scan showed LDA 10mm in diameter in the middle area of the remnant liver. We suspected liver metastasis when both serum CA19-9 and DUPAN-2 levels were elevated with the increasing size of LDA; liver biopsy was then performed, and he was diagnosed with liver metastasis of intrahepatic cholangiocarcinoma. After 3 courses of combination chemotherapy containing GEM and CDDP, a CT scan revealed that the liver metastasis reduced in size, and PR was achieved based on the RECIST standard. After 12 courses, the liver metastasis disappeared, and the patient had achieved CR based on the RECIST standard. The patient has received S-1 following the combination chemotherapy and survived for 6 years since initial treatment without any other metastatic lesions.

[A Case of Splenic Metastasis from Serous Surface Papillary Carcinoma of the Peritoneum Treated by Laparoscopic Splenectomy].

A 50-year-old woman with abdominal fullness, lower abdominal pain, elevated serum CA125, and ascites, underwent neoadjuvant chemotherapy with 6 courses of PTX/CBDCA followed by total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and intrapelvic peritoneal stripping based on a diagnosis of serous surface papillary carcinoma(SSPC) of the peritoneum. Complete response(CR)was shown after adjuvant chemotherapy with 3 courses of the same regimen. After 6 months, serum CA125 level re-increased and abdominal CT showed small low density areas in the patient's spleen and the perisplenic fat tissue. After the additional chemotherapy with 3 courses of PTX/CBDCA were performed based on a diagnosis of metastatic lesion from SSPC, anaphylactic shock occurred as the severe adverse event. The patient was given 9 more courses of the chemotherapy changed the regimen to PTX/CDDP. The splenic metastatic lesion had grown rapidly in the followed CT and then, laparoscopic splenectomy with peritoneal resection was performed based on a diagnosis of splenic metastasis from SSPC. The pathological examinations showed the tumor to be a splenic metastasis and peritoneal dissemination from SSPC. No recurrent lesion has been detected in the 9 months since removal of the splenic metastasis without adjuvant chemotherapy and the patient has survived for 4 years and 6 months since initial treatment.

Case Report: Pulmonary Tumor Thrombotic Microangiopathy in a Cervical Cancer Patient.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rapidly progressive and often fatal pulmonary disease induced by tumor emboli within the small pulmonary arteries. PTTM presents clinically as progressive hypoxia and pulmonary hypertension. Most cases of PTTM are caused by an adenocarcinoma of the stomach. We present the first case report of PTTM caused by cervical squamous cell carcinoma. An 82-year-old woman presented with vaginal bleeding and exertional dyspnea. A cervical mass biopsy showed squamous cell carcinoma. Computed tomography revealed ground glass opacity of the bilateral peripheral lung fields. Hypoxia and pulmonary hypertension gradually worsened after admission. Treatment for acute heart failure was started, but was ineffective. She died of respiratory failure 31 days after admission. She was diagnosed at autopsy as having PTTM induced by cervical squamous cell carcinoma. PTTM needs to be considered in any patient with advanced cancer and lung-related issues to rule out metastatic disease, even in the absence of imaging findings.

Surplus adsorption of bromide ion into π-conjugated carbon nanospaces assisted by proton coadsorption.

Nanoporous carbons can preferentially adsorb bromide ions from an aqueous solution of alkali metal bromides, even on π-conjugated surfaces. Our results show a new adsorption mechanism whereby coadsorption of protons enhances the adsorption of the anions onto the carbons.

An iron(II) complex tripodally chelated with 1,1,1-tris(pyridin-2-yl)ethane showing room-temperature spin-crossover behaviour.

The spin-crossover phenomenon is a reversible low- and high-spin transition caused by external stimuli such as heat. In the novel iron(II) complex salt tetraphenylphosphonium tris(thiocyanato-κN)[1,1,1-tris(pyridin-2-yl)ethane-κ3N,N',N'']ferrate(II), (C24H20P)[Fe(NCS)3(C17H15N3)], the Fe-N bond lengths are in the range 2.027 (2)-2.089 (2) Å, indicating that the specimen consists of comparable molar fractions of the low- and high-spin species at 296 K. A magnetic study confirmed that spin-crossover takes place at around 290 K.

[A Case of Curatively Resected Locally Advanced Cancer of the Pancreatic Body Treated by Distal Pancreatectomy with En Bloc Celiac Axis Resection after Preoperative Intensive Treatment].

A 70-year-old woman with locally advanced pancreatic body cancer invading the celiac axis underwent 4 courses of preoperative chemotherapy consisting of gemcitabine(GEM)plus nab-paclitaxel(nab-PTX)on days 1, 8, and 15 every 4 weeks, followed by radiation therapy(CRT; 50.4Gy delivered in 28 daily fractions). The tumor size was greatly diminished and levels of all tumor markers were decreased. R0resection by distal pancreatectomy with en bloc celiac axis resection(DP-CAR)was performed. The histopathologic findings showed that the effect of CRT was grade 2b(Evans' classification), and the surgical margins were histologically clear. After the surgery, S-1 was administered continuously. The patient shows no signs of recurrence 1 year after surgery.

Rare Primary Adenocarcinoma of the Broad Ligament: Report of Two Cases and a Literature Review.

Malignant primary tumors arising in the uterine broad ligament are extremely rare, and only 26 cases have been reported to date. We describe 2 new cases of primary adenocarcinoma of the broad ligament, and we review the previous literature on such rare tumors. In Case 1, a 71-year-old woman presented with a 2-month history of increased yellow vaginal discharge and lower abdominal pain during bowel movement. Transvaginal sonography revealed a 6.5 cm mass located on the dorsum of the uterus and a 7.0 cm mass (with cystic and solid parts) near the right adnexa. We postoperatively diagnosed the mass as a high-grade serous carcinoma of the broad ligament (pT3cNXM0). The patient is currently receiving adjuvant chemotherapy with paclitaxel and carboplatin. In Case 2, during a complete medical checkup a 43-year-old woman was found to have a pelvic mass indicative of leiomyoma. Transvaginal sonography revealed a 3.8 cm mass located on the dorsum of the uterus. Following surgery, we diagnosed the mass as a clear cell adenocarcinoma of the broad ligament (pT2bN1M0). This patient is also now receiving adjuvant chemotherapy with paclitaxel and carboplatin.

Axillary lymph node recurrence after sentinel lymph node biopsy performed using a combination of indocyanine green fluorescence and the blue dye method in early breast cancer.

BACKGROUND: There is limited information on indocyanine green (ICG) fluorescence and blue dye for detecting sentinel lymph node (SLN) in early breast cancer. A retrospective study was conducted to assess the feasibility of an SLN biopsy using the combination of ICG fluorescence and the blue dye method. METHODS: Seven hundred and fourteen patients with clinically node-negative breast cancer were included in this study. They underwent SLN biopsy using a combination of ICG fluorescence and the blue dye method from March 2007 to February 2014. The ICG (a fluorescence-emitting source) and patent blue (the blue dye) were injected into the patients' subareolar region. The removed lymph nodes that had ICG fluorescence and/or blue dye uptake were defined as SLNs. The results of the SLN biopsies and follow-up results of patients who underwent SLN biopsy alone were investigated. RESULTS: In 711 out of 714 patients, SLNs were identified by a combination of ICG fluorescence and the blue dye method (detection rate, 99.6 %). The average number of SLNs was 2.4 (range 1-7), and the average number of resected swollen para-SLNs was 0.4 (range 0-5). Ninety-nine patients with an SLN and/or para-SLN involvement during the intraoperative pathological diagnosis underwent axillary lymph node resection (ALND). In addition, two of three patients whose SLN was not identified also underwent ALND. In 46 of 101 patients with an ALND, non-SLN involvement was not found. Follow-up results were analyzed in 464 patients with invasive carcinoma excluding those with ductal carcinoma in situ (n = 148) and those who underwent ALND (n = 101). During the follow-up period (range 4.4-87.7 months; median, 38 months), two patients (0.4 %) developed axillary lymph node recurrence. They were successfully salvaged, and to date, no further locoregional recurrence has been observed. CONCLUSIONS: A high rate of SLN detection and low rate of axillary lymph node recurrence were confirmed by an SLN biopsy using a combination of ICG fluorescence and the blue dye method. Therefore, it is suggested that this method may replace the combination of dye and radioisotope methods.

[Hepatic Resection of Multiple Liver Metastases from Gastric Cancer after Molecular Targeted Chemotherapy(S-1 plus Cisplatin plus Trastuzumab)].

A 62-year-old man was diagnosed with gastric cancer and underwent distal gastrectomy, and D1+b lymph node dissection. He was diagnosed postoperatively with T1b (sm2) N0M0, StageⅠA gastric adenocarcinoma and did not receive any adjuvant chemotherapy after surgery. One year and 6 months after gastrectomy, blood analysis indicated high levels of carcinoembryonic antigen (CEA 262.1 ng/mL) while abdominal computed tomography (CT) revealed multiple liver tumors (S7: 15 mm, S7/8: 20 mm). The patient was diagnosed with metachronous multiple liver metastases from gastric cancer. Chemotherapy, combined with molecular targeted therapy (S-1 plus cisplatin [CDDP] plus trastuzumab), was administered because of overexpression of the human epidermal growth factor receptor 2 (HER2) protein in the primary tumor as assessed by immunohistochemistry, the CEA levels decreased immediately after 2 cycles of the chemotherapy, and the liver metastases shrank markedly with no evidence of new lesions on abdominal CT. However, after treatment, Grade 3 neutropenia and diarrhea were observed. Chemotherapy was suspended and hepatic resection was performed. After hepatic resection, the liver tumors were histologically evaluated as Grade 2 metastatic gastric adenocarcinoma, and the HER2 expression of remnant carcinoma cells was established. The patient has been in good health and remained free of recurrences in the 2 years and 3 months after the liver resection. Surgery with preoperative chemotherapy (S-1 plus CDDP plus trastuzumab) can be an effective treatment for liver metastasis from HER2-positive gastric cancer.

[A case of advanced hepatocellular carcinoma successfully treated by liver resection after complete response induced by sorafenib administration].

A 50-year-old man presented to our hospital with the chief complaint of right hypochondriac pain and a palpable tumor. Advanced hepatocellular carcinoma (HCC) and chronic hepatitis B infection were diagnosed and treated by twice-repeated transcatheterarterial chemoembolization (TACE) followed by administration of entecavir. Two months after the last TACE, alpha-fetoprotein(AFP)and protein induced by vitamin K absence or antagonistII (PIVKA-II) levels had elevated, and multiple small early enhancing nodules were detected on computed tomography(CT)scan. Based on his age and liver function (Child-Pugh score A5), a full dose of sorafenib (800 mg/day) was administered. The sorafenib dose was decreased after one month to 400mg/day because of hand-foot syndrome. Following sorafenib administration, the lesions shrank markedly, and complete response (CR) according to modified Response Evaluation Criteria In Solid Tumors(mRECIST)was achieved within 4 months. Six months after sorafenib treatment was begun, recurrent HCC was detected in segment 6, near the previously treated lesion. The decreased size of the main tumor and normalization of AFP levels allowed curative surgical resection. The patient was discharged 5 days after surgery and is currently treated with a half dose of sorafenib. Thirteen months after surgery, a small early enhancing lesion is visible on postoperative CT scan, but AFP and PIVKA-II levels are still keeping in a normal range. This case demonstrates that if sorafenib treatment is effective, then subsequent surgical treatment can be reconsidered in patients with advanced HCC responding to this combined therapy.

Novel image analysis method using ultrasound elastography for noninvasive evaluation of hepatic fibrosis in patients with chronic hepatitis C.

It has been established that the long-term infection of chronic hepatitis C leads to the increased risk of hepatic fibrosis and hepatocellular carcinoma. Currently, histological diagnosis by invasive and painful liver biopsy is the gold standard for evaluating the hepatic fibrosis stage. Because of a side effect or patient inability to cope with the pain, it is difficult to assess the fibrosis stage frequently using liver biopsy. Recently, instead of liver biopsy, many articles have been published showing the usefulness of ultrasound elastography to evaluate the stage of hepatic fibrosis. We also reported the usefulness of real-time tissue elastography (RTE) for liver fibrosis staging in 2007. However, in our previous report, fibrosis classification was performed manually and the number of patients involved was also small. In the current study, the fibrosis staging is performed automatically using software by characterizing the elastography images. We have also increased the number of patients from 64 to 310. Thus, the aim of this study is to increase objectivity by using a newly developed automatic analysis method. We obtain the Liver Fibrosis Index (LFI), which is calculated from image features of RTE images, using multiple regression analysis performed on clinical data of 310 cases as the training data set. The correlation coefficient obtained between the LFI and the stage of hepatic fibrosis was r = 0.68, and significant differences exist between all stages of fibrosis (p < 0.001). Our new method seems promising since it has the ability to diagnose fibrosis even in the presence of inflammation.

[A case of infiltrating transitional cell carcinoma of kidney difficult to distinguish from xanthogranulomatous pyelonephritis].

The patient, a 67-year-old man, initially visited another institution with asymptomatic macroscopic hematuria as the major complaint. Since imaging revealed a tumor occupying the left kidney, he was referred to our hospital. Computed tomography (CT) was suggestive of a tumor involving the renal pelvis that had infiltrated the renal parenchyma. The patient was scheduled for surgery, which was postponed when pre-operative CT indicated a reduction in the tumor size, leading to a subsequent diagnosis of xanthogranulomatous pyelonephritis. Surgery was eventually conducted to address complaints such as persistent hematuria. The pathological diagnosis was infiltrating transitional cell carcinoma of the kidney. Urinary cytodiagnoses were class II-III throughout the observation period.

[A case of prostate cancer that developed following transurethral resection of the prostate: diagnostic efficiency of diffusion-weighted images on magnetic resonance imaging].

An 84-year-old man underwent transurethral resection of the prostate (TURP) with a diagnosis of prostatic hypertrophy at the age of 78. He had a moderately high prostate specific antigen (PSA) level of 4.5 ng/ml before TURP, but without pathological malignancy. Following surgery, his PSA level dropped to 1.7 ng/ml and the patient recovered almost completely. Four years later, however, he underwent a reexamination due to diminished urinary flow. His PSA at that time was 5.2 ng/ml, continuing to rise slowly thereafter. Six years following surgery, his PSA reached 13.7 ng/ml, and the diffusion-weighted image on magnetic resonance imaging showed a high intensity area in the prostatic portion of the urethra. A poorly differentiated adenocarcinoma was detected in TUR-derived tissue fragments of the tumor protruding from the prostate. Tissue obtained via a systematic needle biopsy showed no signs of malignancy. Hormonal therapy was introduced. Five months later, the PSA level fell to 0.130 ng/ml ; the patient is now in clinical follow-up.