Using the DNA Integrity Number to Analyze DNA Quality in Specimens Collected from Liquid-Based Cytology after Fine-Needle Aspiration of Breast Tumors and Lesions.

INTRODUCTION: Cancer genome analysis using next-generation sequencing requires adequate and high-quality DNA samples. Genomic analyses were conventionally performed using formalin-fixed paraffin-embedded sections rather than cytology samples such as cell block or smear specimens. Specimens collected from liquid-based cytology (LBC) have the potential to be sources of high-quality DNA suitable for genetic analysis even after long-term storage. METHODS: We collected breast tumor/lesion fractions from 92 residual LBC specimens using fine-needle aspiration (FNA) biopsy, including breast carcinoma (1 invasive carcinoma and 4 ductal carcinomas in situ), papillomatous lesion (5 intraductal papillomas), and fibroepithelial lesion (19 phyllodes tumors and 53 fibroadenomas) samples, and others (1 ductal adenoma, 1 hamartoma, 1 fibrocystic disease, and 7 unknown). DNA was extracted from all samples and subjected to DNA integrity number (DIN) score analysis. RESULTS: Average DIN score collected from 92 LBC specimens was significantly higher score. In addition, high-quality DNA with high DIN values (7.39 ± 0.80) was successfully extracted more than 12 months after storage of residual LBC specimens. CONCLUSION: Residual LBC specimens collected from FNA of the breast were verified to carry high-quality DNA and could serve as an alternate source for genetic analysis.

[Laparoscopic Abdominoperineal Resection of the Rectum in a Case with Pagetoid Spread of Anal Canal Carcinoma].

The patient, a man in his 60s, first noticed an elevated lesion around the anus 3 years ago. The lesion failed to subside with the topical drug preparations prescribed at a local clinic, and the patient was referred to the Department of Dermatology of our hospital for further workup and treatment. The findings of biopsy from the lesion suggested skin infiltration of anal canal carcinoma, and the patient was referred to the Department of Surgery. Examination here revealed only induration of the anal canal, with no abnormality of the rectal mucosa even when the endoscope was reversed to visualize the rectum. Examination by various imaging modalities failed to reveal any metastases to the lymph nodes or distant organs, and the primary lesion remained unidentified. Laparoscopic abdominoperineal excision of the rectum was performed, beginning with anal manipulation. First, a 15-mm margin was set on the skin from the tumor edge, and the skin stump was divided into 4 equal portions. After confirming by rapid intraoperative frozen-section examination that the margin was negative along the full circumference, anal manipulation was performed, leaving a distance in the vertical direction immediately below the tumor. Upon completion of the anal manipulation, intraperitoneal manipulation was performed in a routine manner. The anal skin was relaxed subcutaneously, as done during mastectomy, and the subsequent suture closure could be done smoothly. The tumor was classified as pT1bN0M0, pStage Ⅰ. The experience with this case indicates that biopsy should be proactively employed for the diagnosis in such cases, and that proactive skin biopsy is useful when dealing with intractable anal skin lesions.

[A Case of Recurrent Gastric GIST Who Survived for Long after Laparoscopic Resection and Imatinib Therapy].

A man patient in his 70s underwent left nephrectomy and laparoscopic partial gastrectomy for the treatment of a left renal cell carcinoma and gastrointestinal stromal tumor(GIST)arising from the stomach. Histopathologically, both the renal cell carcinoma and GIST were kit-positive, CD34-positive, and S-100 protein-negative, and the Ki-67 index was about 40% as determined by the hot spot method, so that it was diagnosed as an intermediate-group GIST. After surgery, the patient was followed without adjuvant therapy, as he did not wish to receive postoperative chemotherapy. A computed tomography(CT)conducted 3 years after the surgery revealed tumorous shadows in the abdominal wall, inferior periesophageal region, and dorsal aspect of the pancreas. Positron emission tomography(PET)-CT showed fluorodeoxyglucose(FDG) accumulation in these lesions. Therefore, based on a suspicion of recurrent renal cell carcinoma or GIST, we carried out abdominal wall tumor resection for both exploratory and diagnostic purposes, which yielded histopathological diagnosis of GIST, with features similar to those observed at the time of the initial operation. Because the number of tumors remained unchanged during the subsequent follow-up period, the tumorous lesions in the periesophageal region and on the dorsal aspect of the pancreas were resected laparoscopically. Each of the resected tumors showed histological features consistent with GIST. The patient was started on oral imatinib therapy after this operation. To date(5 years after the surgery for the recurrent tumors and 8 years after the initial operation), the patient has remained free of recurrence. The pattern of tumor recurrence noted in the present case(ie, metastasis/dissemination to the skeletal muscles)is relatively rare, and few reports have been published concerning long-term survivors through multidisciplinary treatment (surgical treatment and others). We report this case with a review of the literature.

[A Case of Unresectable Advanced Gastric Cancer Successfully Treated with Conversion Surgery].

A man in his 70s consulted a local clinic with a chief complaint of difficulty eating. Upper gastrointestinal endoscopy revealed a type 4 tumor spreading irregularly from immediately below the esophageal cardia to the lower gastric body. The patient was referred to our hospital with a diagnosis of advanced gastric cancer(human epidermal growth factor receptor 2 [HER2]-positive moderately-differentiated adenocarcinoma)accompanied by lymph node enlargement. We planned an open total gastrectomy after staging laparoscopy to rule out dissemination because peritoneal dissemination could not be ruled out using computed tomography(CT). To perform a total gastrectomy, a celiotomy was done after staging laparoscopy results suggested that dissemination was unlikely. However, the border between the pericardial lymph nodes and the pancreas or peritoneal artery was not visible, forcing us to terminate the staging laparotomy based on a judgment of unresectable locally advanced gastric cancer. Therefore, the patient was administered 6 cycles of combined S-1/CDDP plus trastuzumab as the primary therapy. The response to therapy was favorable, and we scheduled a surgical resection. However, the scheduled surgery was rescheduled because of COVID-19 pneumonia, and R0 resection was finally performed after the 7th cycle of S-1/CDDP plus trastuzumab therapy. Histopathologically, the regional lymph node metastasis had disappeared, the viable tumor remained within the mucosal layer, and scarring was evident from the submucosal layer to the serosa. In recent years, conversion surgery for unresectable gastric cancer has been sporadically reported. However, we are unable to definitively opine on whether this kind of surgery may contribute to improving the prognosis, resection remains indispensable for radical treatment. We report this case along with a review of the literature.

[A Case of Triple Negative Breast Cancer with Successful Control of Recurrent Disease Activity for More than Ten Years].

A woman in her 70s underwent mastectomy plus axillary lymph node excision(Bt plus Ax)in December 2011 for left breast cancer classified as pT2N1M0, pStage ⅡB. The tumor was identified as an invasive ductal carcinoma(IDC), neural/ glial antigen 2(NG2), pT2(35 mm), INF γ, ly2, v0, g+, f+, s+, extensive intraductal component(EIC)-negative, ICT- positive, NCAT-positive, n(4/18), estrogen receptor(ER)-negative, progesterone receptor(PgR)-negative, human epidermal growth factor receptor 2(HER2)-negative, Ki-67 30-40%. Postoperative adjuvant fluorouracil plus epirubicin HCl plus cyclophosphamide(FEC)plus paclitaxel(PTX)therapy was administered. The patient refused to undergo postoperative radiation therapy. Two years after the surgery, she was diagnosed as having a lung metastasis and local disease recurrence. Biopsy of the local recurrent lesion revealed the same histopathological diagnosis as before. Capecitabine was selected for treatment of the recurrent lesion. After 2 years of capecitabine treatment, the response was rated as progressive disease (PD). At this time, eribulin mesylate was selected, along with intensity-modulated radiation therapy(IMRT). This resulted in disappearance of the tumor on imaging. However, considering that the histological findings did not suggest complete response(CR)and that the tumor was triple-negative(TN), we adopted a strategy of continuing the drug therapy at reduced dose level. With this strategy, the disease activity could be successfully controlled for 6.5 years. Subsequently, liver metastasis was detected, and the drug was switched to vinorelbine ditartrate(a drug with less non-hematological toxicity). Meanwhile, a breast cancer susceptibility gene(BRCA)analysis was performed in January 2021, which was negative. Subsequently, in September 2021, we obtained a positive result for PDL1-SP142 and negative result for 22C3. About half a year later, ie, in October 2021(11 years after the surgery), we detected an increase in the size of the liver metastasis and selected atezolizumab and nab-PTX for treatment. Applicable regimens of drug therapy are still available at present and drug therapy has been continued based on a discussion and mutual understanding of the adverse reactions, etc. with the patient. Few reports have been published concerning long-term survivors among TN breast cancer cases.

Establishment of a deep-learning system to diagnose BI-RADS4a or higher using breast ultrasound for clinical application.

Although the categorization of ultrasound using the Breast Imaging Reporting and Data System (BI-RADS) has become widespread worldwide, the problem of inter-observer variability remains. To maintain uniformity in diagnostic accuracy, we have developed a system in which artificial intelligence (AI) can distinguish whether a static image obtained using a breast ultrasound represents BI-RADS3 or lower or BI-RADS4a or higher to determine the medical management that should be performed on a patient whose breast ultrasound shows abnormalities. To establish and validate the AI system, a training dataset consisting of 4028 images containing 5014 lesions and a test dataset consisting of 3166 images containing 3656 lesions were collected and annotated. We selected a setting that maximized the area under the curve (AUC) and minimized the difference in sensitivity and specificity by adjusting the internal parameters of the AI system, achieving an AUC, sensitivity, and specificity of 0.95, 91.2%, and 90.7%, respectively. Furthermore, based on 30 images extracted from the test data, the diagnostic accuracy of 20 clinicians and the AI system was compared, and the AI system was found to be significantly superior to the clinicians (McNemar test, p < 0.001). Although deep-learning methods to categorize benign and malignant tumors using breast ultrasound have been extensively reported, our work represents the first attempt to establish an AI system to classify BI-RADS3 or lower and BI-RADS4a or higher successfully, providing important implications for clinical actions. These results suggest that the AI diagnostic system is sufficient to proceed to the next stage of clinical application.

A case report of Kuttner tumor mimicking a malignant tumor, leading to overtreatment.

Preoperative diagnosis with multimodal approaches might lead to overtreatment. Cautious understanding of cytology and dynamic contrast-enhanced magnetic resonance imaging is required when a Kuttner tumor is cited as differential diagnosis.

Erratum to immediate breast volume replacement using a free dermal fat graft after breast cancer surgery: multi-institutional joint research of short-term outcomes in 262 Japanese patients.

[This corrects the article on p. 179 in vol. 4, PMID: 26005649.].

Immediate breast volume replacement using a free dermal fat graft after breast cancer surgery: multi-institutional joint research of short-term outcomes in 262 Japanese patients.

BACKGROUND: Immediate volume replacement using a free dermal fat graft (FDFG) has been proven safe with early postoperative benefits. The aims of the present study were to clarify adequate indications and risk factors associated with operative morbidity. PATIENTS AND METHODS: A multi-institutional analysis of partial mastectomy with immediate volume replacement with FDFG was undertaken in 14 hospitals specializing in breast cancer treatment. Clinical and oncological variables were analyzed to identify factors associated with postoperative complications. RESULTS: A total of 262 cases were analyzed. Considering the observation period and overlap of patients, 13 (5.4%) out of 242 patients had complications within 1 month of surgery while 7 (4.6%) out of 151 patients developed complications 1-12 months after surgery. Two hundred and eleven out of 242 patients were statistically examined using a multivariate analysis, which revealed that the weight of resected breast tissue, size of implanted FDFG (cranio-caudal length), and weight of implanted FDFG were associated with a higher likelihood of postoperative complications. CONCLUSIONS: Immediate breast volume replacement using a FDFG after breast cancer surgery should be done for selected patients with breast cancer to avoid postoperative complications. The prospective and larger investigations are warranted for the establishment of appropriate guidelines.

Synchronous bilateral neuroendocrine ductal carcinoma in situ.

Neuroendocrine ductal carcinoma in situ (NE-DCIS) is a breast malignancy that has characteristic clinicopathological features and can, therefore, be regarded as a distinct variant of DCIS. The patient was a 54-year-old premenopausal woman with hemorrhagic nipple discharge in her left breast. Magnetic resonance imaging and ultrasound (US) images of the left breast showed mass-like lesions, while concurrent images of the right breast showed non-mass-like lesions. These findings suggested the presence of both benign and malignant tumors. Pathological findings from US-guided core-needle biopsy of the left mass were highly suspicious of a malignant tumor. Excisional biopsy of both breasts was performed. We could define the diagnosis of breast cancer by the second opinion on pathological diagnosis. The tumor cells showed histological characteristics of NE-DCIS. Bilateral breast lesions had histopathological similarities and were composed of predominantly solid growth of carcinoma cells, frequently with well-developed vascular structures, in mammary ducts and ductules. Carcinoma cells were polygonal or occasionally spindle shaped and had fine-granular, relatively eosinophilic cytoplasm. The nuclei of these cells showed round to ovoid in shape and fine-granular chromatin pattern. There was not any invasive component, as confirmed by careful histological examination. Thus, additional immunohistochemical stainings for NE markers (chromogranin A and synaptophysin) were performed. Staining statuses of these markers were positive in almost all tumor cells from both breasts. Both tumors were therefore diagnosed as NE-DCIS. To our knowledge, this case is the first report of NE-DCIS diagnosed synchronously in both breasts.

A case of congenital unilateral amastia.

Numerous reports have been published regarding the reconstruction of the breast, but the majority of these reports focus on breast reconstruction for defects caused by the removal of breast cancers. The authors treated a rare case of unilateral amastia where a 54-year-old female had a complete absence of the breast on one side, though the breast on the other side was intact. The defect was reconstructed successfully with a transverse rectus abdominis myocutaneous flap (TRAM) flap. The present study introduces this rare case with reference to past reports of amastia.

The role of contrast enhanced MRI in the diagnosis of non-mass image-forming lesions on breast ultrasonography.

BACKGROUND: Although non-mass lesions on breast ultrasonography have become relatively common, they remain very difficult to diagnose. The purpose of this study was to evaluate the usefulness of contrast enhanced magnetic resonance imaging (MRI) in managing non-mass lesions. METHODS: A total of 82 cases of non-mass lesions visible on breast ultrasonography who were subjected to contrast enhanced MRI (CE-MRI) were available for assessment. These lesions were evaluated in terms of the association between the enhancement pattern on contrast enhanced MRI and the pathological or cytological diagnosis. RESULTS: Thirty-three of 82 (40.2%) non-mass image-forming lesions were seen as enhanced lesions on CE-MRI, of which 32 revealed non-masslike enhancements. Of the 19 breast cancers detected as non-mass image-forming lesions, 18 (94.7%) had an enhancement pattern not suggestive of a mass, so breast cancers comprised 56.3 % (18/32) of the lesions. Most of the breast cancers tended to emerge in a setting of duct dilatation with internal echoes (45.5%; 5/11) or low echo areas with indistinct margins (32.4%; 11/34). Morphologically, segmental (57.9%; 11/19) and regional (21.1%; 4/19) enhancements were common patterns of breast cancer which showed up as non-mass image-forming lesions. On the other hand, 49 of 82 (59.8%) non-mass image-forming lesions were not enhanced and 28 of 49 cases underwent pathological examination. Only one case was breast cancer with category 5 microcalcifications and although about half of the remaining 21 cases were followed for at least 12 months, no breast cancers were found. CONCLUSION: Contrast enhanced MRI was useful for detecting breast cancer in cases of non-mass image-forming lesions. On the other hand, except for cases in which mammography was suspicious for malignancy, lesions showing no enhanced areas may be safely followed, because the possibility of breast cancer is minute.

Isolated splenic vein thrombosis secondary to splenic metastasis: a case report.

A 49-year-old, previously healthy woman sought treatment for abdominal pain. Colonoscopy revealed ascending colon cancer. Computed tomography and angiography showed splenic metastasis and thrombosis extending from the splenic vein to the portal vein. She underwent right hemicolectomy, splenectomy, and distal pancreatomy. Histological findings showed no malignant cell in the splenic vein which was filled with organizing thrombus. We postulate the mechanism of splenic vein thrombosis in our case to be secondary to the extrinsic compression of the splenic vein by the splenic metastasis or by the inflammatory process produced by the splenic metastasis. In conclusion, we suggest that splenic metastasis should be added to the list of differential diagnosis which causes splenic vein thrombosis. In the absence of other sites of neoplastic disease, splenectomy seems to be the preferred therapy because it can be performed with low morbidity and harbors the potential for long-term survival.

An uncommon case of diabetic mastopathy in type II non-insulin dependent diabetes mellitus.

Diabetic mastopathy is an uncommon tumor-like proliferation of fibrous tissue of the breast that usually occurs in a patient who has suffered from type I diabetes mellitus of long duration. Here we report a rare case of diabetic mastopathy that occurred in type II non-insulin dependent diabetes mellitus. This patient was a 63-year-old postmenopausal woman. Mammography, ultrasonography and MR imaging could not distinguish it from breast cancer. Although the core needle biopsy specimen showed fibrosis without evidence of malignancy, excisional biopsy was performed. Histological findings demonstrated typical diabetic mastopathy with keloid-like fibrosis, perivascular lymphocytic infiltration, and lymphocytic lobulitis without evidence of malignancy. These lymphocytes were composed predominantly of B-cells. Five months after surgical biopsy, a nodular formation approximately 4 cm in diameter recurred adjacent to the resected end of the biopsy.

Strangulated hernia through a defect of the broad ligament and mobile cecum: a case report.

We report a case of 28-year-old woman presenting with small bowel obstruction. She had neither prior surgery nor delivery. An upright abdominal radiograph revealed several air-fluid levels in the small bowel in the midabdomen and the pelvic cavity. Computed tomography demonstrated a dilated small bowel loop in the Douglas's fossa,but no definite diagnosis could be made. Supportive therapy with draining the intestinal fluid by a long intestinal tube did not result in improvement,which suggested the possibility of a strangulated hernia. Exploratory laparotomy revealed mobile cecum and a 20-cm length of the ileum herniated into a defect of the right broad ligament. As a gangrenous change was recognized in the incarcerated bowel, its resection was carried out,followed by end-to-end anastomosis and closure of the defects of the broad ligament. The postoperative course was uneventful. Intestinal obstruction is a very common cause for presentation to an emergency department,while internal hernia is a rare cause of obstruction. Among internal hernias, those through defects of the broad ligament are extremely rare. Defects of the broad ligament can be either congenital or secondary to surgery, pelvic inflammatory disease,and delivery trauma. In conclusion, we emphasize that hernia of the broad ligament should be added to the list of differential diagnosis for female patients presenting with an intestinal obstruction. Early diagnosis and surgical repair reduce morbidity and mortality from strangulation.