A Nationwide Study on HER2-low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols.

Purpose: Notable effectiveness of trastuzumab deruxtecan (T-DXd) in patients with HER2-low advanced breast cancer (BC) has focused pathologists' attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from twenty-five institutions included in this study. Of these patients, 40.7% (range: 6.0%-76.3%) were classified as HER2-zero, 41.7% (range: 10.5%-69.1%) as HER2-low, and 17.5% (range: 6.7%-34.0%) as HER2-positive. HER2-low tumors were associated with positive ER and PR statuses (p<0.001 and p<0.001, respectively). Antigen retrieval times (≥ 36 min vs. < 36 min) and antibody incubation times (≥ 12 min vs. < 12 min) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy (CNB) and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3259) of the patients. Conclusion: The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Effectiveness of high-dose progestin and long-term outcomes in young women with early-stage, well-differentiated endometrioid adenocarcinoma of uterine endometrium.

PURPOSE: We assessed the effectiveness of high-dose progestins as a conservative treatment in young women with endometrial adenocarcinoma. METHODS: We retrospectively reviewed the hospital data of patients with endometrial cancer that were managed conservatively. Of those women with grade 1 endometrioid endometrial adenocarcinoma, we included those who were younger than 40 years and in whom the disease was clinically confined to the endometrium. A complete response was defined pathologically as the absence of tissue with adenocarcinoma or hyperplasia. RESULTS: Fourteen patients were included. Their mean age was 30.0 ± 4.8 years and the mean follow-up period was 47.3 ± 29.7 months. Twelve patients received 30-500 mg/day medroxyprogesterone acetate and two received 160 or 240 mg/day megestrol acetate. The median duration of treatment was 6 months (range 3-15 months) and 13 (93%) patients showed a complete response. Endometrial pathology reappeared in four patients (4/13, 31%) including two relapses, three of whom developed after the patients gave birth. Six patients used a combined oral contraceptive or a progestin-releasing intrauterine device as a maintenance therapy and experienced no recurrence. Four women (4/7, 57%) conceived successfully seven times with assisted-reproductive technology. No adverse effects of the progestins or tumor-related death were noted. CONCLUSIONS: High-dose progestin therapy can be an effective conservative treatment in young patients with well-differentiated early-stage endometrial cancer. If patients wish to preserve their fertility even after they have completed childbearing, maintenance therapy with a cyclic oral contraceptive or a progestin-releasing intrauterine device may be an option to prevent recurrence.

Isolation of genes involved in pancreas regeneration by subtractive hybridization.

The deterioration of ß cells in the pancreas is a crucial factor in the progression of diabetes mellitus; therefore, the recovery of ß cells is of vital importance for effective diabetic therapeutic strategies. Partially pancreatectomized rats have been used for the investigation of pancreatic regeneration. Because it was determined that tissue extract from the partially-dissected pancreas induces pancreatic differentiation in embryonic stem cells, paracrine factors were thought to be involved in the regeneration. In this study, we screened for genes that had higher mRNA levels 2 days after 60%-pancreatectomy. The genes were isolated using subtractive hybridization and DNA sequencing. Twelve genes (adipsin, Aplp2, Clu, Col1a2, Glul, Krt8, Lgmn, LOC299907, LOC502894, Pla2g1b, Reg3α and Xbp1) were identified, and RT-PCR and real-time PCR analyses were performed to validate their expression levels. Among the genes identified, three genes (Glul, Lgmn and Reg3a) were selected for further analyses. Assays revealed that Glul and Reg3α enhance cell growth. Glul, Lgmn and Reg3α change the expression level of islet marker genes, where NEUROD, NKX2.2, PAX4 and PAX6 are up-regulated and somatostatin is down-regulated. Thus, we believe that Glul, Lgmn and Reg3a can serve as novel targets in diabetes mellitus genetic therapy.

Successful in vitro fertilization pregnancy and delivery after a fertility-sparing laparoscopic operation in a patient with a papillary thyroid carcinoma arising from a mature cystic teratoma.

Malignant transformation of ovarian mature cystic teratomas is rare, and papillary thyroid cancer occurs in 0.1%-0.3% of ovarian teratomas that undergo malignant transformation. We describe a case of successful in vitro fertilization pregnancy and delivery after a fertility-sparing laparoscopic operation in a patient with papillary thyroid carcinoma arising from a mature cystic teratoma.

Does Physician Leadership Influence Followers' Hand Hygiene Compliance?

The aim of this study was to determine factors influencing the hand hygiene compliance of a physician. We found a strong correlation between a leader's (staff member's or fellow's) and a follower's (resident's) hand hygiene compliance. Followers' appropriate hand hygiene compliance was significantly associated with the compliance of the leader (P = .01).

Delayed recovery of a patient with obstructive azoospermia and a history of acute epididymitis.

Obstructive azoospermia caused by acute epididymitis is usually permanent, and microsurgical vasoepididymostomy is the only reconstructive treatment option. There have been no reports of delayed recovery of sperm count after over 1 year in a patient with obstructive azoospermia related to history of acute epididymitis. We present a young male patient who had azoospermia and a history of acute epididymitis who experienced delayed recovery, with complete restoration of sperm production and the ability to conceive naturally.

Histologic influence of doxazosin and finasteride in benign prostatic hyperplasia accompanying chronic inflammation.

AIM: To evaluate the influence of doxazosin and finasteride on histologic findings in benign prostatic hyperplasia accompanied by prostatitis, and to examine the factors related with prostate carcinogenesis. MATERIALS AND METHODS: Prostate tissue from 17 cases of prostatic hyperplasia were divided into three groups; group 1: no medication history, group 2: both doxazosin and finasteride for at least 6 months before surgery; group 3: doxazosin for a minimum of 6 months before transurethral resection. Formalin-fixed, paraffin-embedded sections were stained with hematoxylin and eosin stain and immunohistochemistry for COX-2, CD3, CD68, VEGF, and GSTP (glutathione S-transferase pi). RESULTS: CD3 showed a tendency toward decreased staining intensity and extent in group 3 (p = 0.026, p = 0.004, respectively). CD68 showed a different staining extent among the three groups (p = 0.020). For VEGF, the staining extent showed different results between groups 2 and 3 (p = 0.044). There was no correlation between COX-2 and VEGF in group 1. However, a positive correlation between COX-2 and GSTP1 was demonstrated in group 2 (p = 0.000). CONCLUSIONS: Doxazosin-treated prostate tissue showed decreased inflammatory reaction. GSTP1 expression was decreased in combined treatment with doxazosin and finasteride. These findings suggest that finasteride may interfere with the anti-inflammatory reaction. Finasteride also decreases angiogenesis. However, the meaning of our observations is limited by small sample size.

Clinicopathological Analysis of Ultrasound-guided Vacuum-assisted Breast Biopsy for the Diagnosis and Treatment of Breast Disease.

BACKGROUND/AIM: To evaluate the usefulness and safety of vacuum-assisted breast biopsy (VABB) for breast lesion diagnosis and treatment. PATIENTS AND METHODS: Clinical and histopathological data of 8,748 patients, who underwent 11,221 VABB procedures were analyzed. RESULTS: Most patients (58.2%) were <40 years old. Most lesions (39.6%) were 0.6-1.0 cm in diameter while 3.2% were ≥3.0 cm; fibroadenomas were the most common (46.6%). Eight (14% of 57) cases of atypical ductal hyperplasia were underestimated. The positive predictive values (PPVs) of breast imaging reporting and data system (BI-RADS) ultrasound category were 0.6%, 3.4%, 34.8%, 66.2%, and 93.8% for category 3, 4a, 4b, 4c, and 5 lesions, respectively. The mean number of core specimens was 9.5±8.8; the mean procedure time was 3.4±2.7 min. No residual lesions were found in 94.4% of the 7,480 patients. CONCLUSION: VABB could replace ultrasound-guided core biopsy and surgical excisional biopsy for the diagnosis of breast disease and the treatment of benign breast lesions.

Recurrence Rates and Characteristics of Phyllodes Tumors Diagnosed by Ultrasound-guided Vacuum-assisted Breast Biopsy (VABB).

BACKGROUND/AIM: Recently, the development of ultrasonography (US)-guided vacuum-assisted breast biopsy (VABB) has enabled the excision of benign breast tumors with normal surrounding breast tissues; thus, complete excision is possible without residual tumor tissue. We sought to identify the clinicopathological characteristics and recurrence rates of benign phyllodes tumors diagnosed by US-guided VABB. PATIENTS AND METHODS: Data from 11,221 US-guided VABBs performed at the Gangnam Cha Medical Center over 12 years were analyzed. Eighty-three lesions were diagnosed as benign phyllodes tumors; 67 with >24 months of follow-up data were investigated. All lesions were excised using an 8-gauge probe without residual tissue; patients underwent follow-up US every 3-6 months. RESULTS: Five patients (7.46%) experienced local recurrence during a mean follow-up period of 27.8 months; no distant metastases occurred. The mean tumor size was 3.0 cm in the recurrence group and 1.87 cm in the non-recurrence group (p=0.05). CONCLUSION: Benign phyllodes tumors excised and diagnosed using VABB showed a low recurrence rate during the follow-up period; thus, these tumors, particularly those <3 cm, can be safely monitored with ultrasonography instead of performing immediate re-excision.

Dilatation and curettage is more accurate than endometrial aspiration biopsy in early-stage endometrial cancer patients treated with high dose oral progestin and levonorgestrel intrauterine system.

OBJECTIVE: To determine whether less invasive endometrial (EM) aspiration biopsy is adequately accurate for evaluating treatment outcomes compared to the dilatation and curettage (D&C) biopsy in early-stage endometrial cancer (EC) patients treated with high dose oral progestin and levonorgestrel intrauterine system (LNG-IUS). METHODS: We conducted a prospective observational study with patients younger than 40 years who were diagnosed with clinical stage IA, The International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid adenocarcinoma and sought to maintain their fertility. The patients were treated with medroxyprogesterone acetate 500 mg/day and LNG-IUS. Treatment responses were evaluated every 3 months. EM aspiration biopsy was conducted after LNG-IUS removal followed D&C. The tissue samples were histologically compared. The diagnostic concordance rate of the two tests was examined with κ statistics. RESULTS: Twenty-eight pairs of EM samples were obtained from five patients. The diagnostic concordance rate of D&C and EM aspiration biopsy was 39.3% (κ value=0.26). Of the seven samples diagnosed as normal with D&C, three (42.8%) were diagnosed as normal by using EM aspiration biopsy. Of the eight samples diagnosed with endometrioid adenocarcinoma by using D&C, three (37.5%) were diagnosed with endometrioid adenocarcinoma by using EM aspiration biopsy. Of the 13 complex EM hyperplasia samples diagnosed with the D&C, five (38.5%) were diagnosed with EM hyperplasia by using EM aspiration biopsy. Of the samples obtained through EM aspiration, 46.4% were insufficient for histological evaluation. CONCLUSION: To evaluate the treatment responses of patients with early-stage EC treated with high dose oral progestin and LNG-IUS, D&C should be conducted after LNG-IUS removal.

Differences between the clinical and histopathological tumor stages in breast cancer diagnosed using vacuum-assisted breast biopsy.

The present study aimed to determine the difference between the clinical tumor stage (T stage) based on pre-operative ultrasound and the histopathological T stage subsequent to surgery in vacuum-assisted breast biopsy (VABB)-diagnosed breast cancer. Tumor sizes measured ultrasonography (USG) and histologically were retrospectively calculated and analyzed using paired t-tests in 209 patients diagnosed with breast cancer using VABB. The patients were classified into two groups, consisting of breast imaging reporting and data system (BI-RADS) category 4a or below, who underwent complete resection by VABB, and BI-RADS category 4b or above, who underwent incisional biopsy by VABB. The histopathological tumor size was found to be smaller compared with the USG-determined size in 92.3% of pT1a, 75.5% of pT1b, 44.2% of pT1c, 47.7% of pT2 and 0% of pT3 cases. Furthermore, the histopathological tumor size was smaller compared with the USG-determined size in 62.8% of cases classified as BI-RADS category 3-4a and in 53.7% of cases classified as BI-RADS category 4b-5. The smaller the primary tumor at the time of diagnosis by VABB, the higher the likelihood of pathological underestimation on post-operative histopathological assessment compared to pre-operative USG.

Changes in proliferating and apoptotic markers of leiomyoma following treatment with a selective progesterone receptor modulator or gonadotropin-releasing hormone agonist.

OBJECTIVE: To evaluate changes in proliferating and apoptotic markers of myoma tissue from patients treated with a selective progesterone receptor modulator (SPRM) or GnRH agonist by measuring expression of PDGF-A mRNA, IGF-1 mRNA, bcl-2 mRNA, and PCNA and caspase-3 protein. STUDY DESIGN: Between December 2013 and July 2014, women with symptomatic leiomyoma were divided into control (no treatment before surgery), SPRM (treatment with ulipristal acetate [SPRM] for 3 months before surgery), and GnRHa (treatment with leuprolide acetate [GnRH agonist] for 3 months before surgery) groups. Tissue specimens were collected from the myoma core and normal myometrium of all patients. The expression of mRNA and protein was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot. RESULTS: A total of 38 patients were enrolled (control group, n=14; SPRM group, n=13; GnRHa group, n=11). PDGF-A mRNA expression was lower in both the myoma core and normal myometrium tissues of the SPRM compared with the control group, but there was no difference between the control and GnRHa group. There were also no group differences in bcl-2 mRNA or IGF-1 mRNA expression. Both PCNA and caspase-3 protein expression were higher in the leiomyoma tissue of the SPRM compared with the control group, but there was no difference between the control and GnRHa groups in the expression of either protein. CONCLUSION: Both proliferation and apoptosis were increased in the leiomyoma of patients after SPRM treatment, but there was no change following GnRH agonist treatment, in vivo. However, PDGF-A mRNA was decreased after SPRM treatment, indicating a dual effect of progesterone on the regulation of growth factors. Furthermore, there was an increase in caspase-3 protein, but not bcl-2 mRNA, expression in the SPRM group suggesting that SPRM may exert its effects in pathways other than the bcl-2 apoptotic pathway.

Relationship between utrophin and regenerating muscle fibers in duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a dystrophinopathy, and its associated gene is located on Xp21. Moreover, utrophin, a recently identified structural homologue of dystrophin is reported to be up-regulated in DMD. In order to investigate the association between utrophin and muscle regeneration in DMD, an immunohistochemical study using antibodies to utrophin, dystrophin, vimentin and desmin was carried out in 17 cases of DMD, 3 cases of polymyositis and 1 case of dermatomyositis. Dystrophin was negative in almost all cases of DMD, but positive in all cases of inflammatory myopathy (IM). Utrophin was positive in 94.0% of DMD and in 75.0% of IM. 36.4% of the myofibers were positive in DMD, as compared to 10.5% in IM (p=0.001). In both groups, utrophin positivity was present most commonly in small regenerating fibers (p=0.001, 0.013). Vimentin and desmin were intensely positive in regenerating fibers in all cases of DMD and IM. 34.4% and 35.4% of myofibers were positive for vimentin and desmin in DMD, as compared to 21.8% and 20.9% in IM (p=0.001, 0.001). In both groups, vimentin and desmin positivity were present most commonly in small regenerating fibers (p=0.001, 0.001). The staining intensities of utrophin, vimentin and desmin were also higher in small regenerating fibers. These results show that utrophin up-regulation is regeneration-associated, and that it is proportional to the quantity of regenerating myofibers, but is not specific for DMD.

A case of multiple schwannomas of the trigeminal nerves, acoustic nerves, lower cranial nerves, brachial plexuses and spinal canal: schwannomatosis or neurofibromatosis?

In most cases, while schwannoma is sporadically manifested as a single benign neoplasm, the presence of multiple schwannomas in one patient is usually indicative of neurofibromatosis 2. However, several recent reports have suggested that schwannomatosis itself may also be a distinct clinical entity. This study examines an extremely rare case of probable schwannomatosis associated with intracranial, intraspinal and peripheral involvements. A 63-year-old woman presented with a seven-year history of palpable lumps on both sides of the supraclavicular area and hearing impairment in both ears. On physical examination, no skin manifestations were evident. Facial sensory change, deafness in the left ear and decreased gag reflex were revealed by neurological examination. Magnetic resonance imaging revealed multiple lesions of the trigeminal nerves, acoustic nerves, lower cranial nerves, spinal accessory nerve, brachial plexuses, and spinal nerves. Pathological examination of tumors from the bilateral brachial plexuses, the spinal nerve in the T8 spinal position and the neck mass revealed benign schwannomas. Following is this patient case report of multiple schwannomas presenting with no skin manifestations of neurofibromatosis.

CT findings of surgically verified acute invasive small bowel anisakiasis resulting in small bowel obstruction.

Acute invasive small bowel anisakiasis is an extremely rare cause of small bowel obstruction. The authors report a case of surgically verified small bowel anisakiasis resulting in small bowel obstruction. A 54-year-old man presented with suddenly developed diffuse abdominal pain after ingestion of raw fish. The peripheral blood examination showed leukocytosis without eosinophilia. CT showed a long segment of thickened small bowel accompanied by a focal narrowed portion and combined with ascites. When these findings are noted in patients with a history of recent ingestion of raw or undercooked fish, the diagnosis of small bowel anisakiasis should be considered in order to avoid application of unnecessary surgical treatment, in spite of the severity of the abdominal pain and bowel obstruction.

A case of the rare variant of Klinefelter syndrome 47,XY,i(X)(q10).

Klinefelter syndrome is the most common genetic form of male hypogonadism, but the phenotype becomes evident only after puberty. It is characterized by infertility, small testes, sparse body and facial hair, increased body weight, gynecomastia, increased LH and FSH, and a low level of testosterone. Early recognition and treatment of Klinefelter syndrome can significantly improve the patient's quality of life and prevent serious consequences. Here, we report an infertile man with a rare variant of Klinefelter syndrome with a 47, XY, i(X)(q10) karyotype.

Long-term follow-up result of benign phyllodes tumor of the breast diagnosed and excised by ultrasound-guided vacuum-assisted breast biopsy.

PURPOSE: Percutaneous removal of benign breast tumors using ultrasound-guided vacuum-assisted breast biopsy (VABB) has been recently regarded as a feasible and safe method without serious complications. The aim of this study was to evaluate the efficacy and safety of the VABB in the treatment of benign phyllodes tumors, and to identify whether or not surgical re-excision is necessary for benign phyllodes tumors diagnosed and excised by VABB. METHODS: From January 2003 to December 2011, a total of 6,923 VABB were performed in 5,434 patients. Out of 6,923 lesions, 53 were benign phyllodes tumors. Among these, 31 lesions, with a follow-up period of longer than 24 months, were enrolled in this study. Ultrasonography follow-up was performed at 3 to 6 month intervals in order to assess recurrence. The mean follow-up period was 75.9±13.5 months (range, 24-94 months). RESULTS: The mean patient age at presentation was 31.6±9.4 years. The mean size of the lesion was 1.60±0.88 cm. The majority of lesions, 74.2% (23 cases), were palpable, and 25.8% (8 cases) were non-palpable. Twenty-two lesions (71.0%) were classified as Breast Imaging Reporting and Data System category 3, and nine lesions (29.0%) were classified as category 4a, by ultrasonography. During the follow-up period, local recurrence developed in one lesion, making the local recurrence rate 3.2%. CONCLUSION: If a benign phyllodes tumor is diagnosed, and sufficiently excised by VABB, observing the clinical course may be considered as an alternative to performing immediate wide local excision; this is the case despite the fact that it would need to be observed for a prolonged period of time.

Cellular fibroma of the ovary containing Leydig cell hyperplasia: a case report.

Ovarian stromal tumors containing Leydig cell components are rare. Only a few cases of ovarian stromal Leydig cell tumors characterized by clusters of Leydig cells have been reported to date. Here, we present the first case report of a 65-year-old woman with a cellular fibroma of the ovary containing Leydig cell hyperplasia. Microscopic examination revealed the proliferation of spindle cells arranged in intersecting bundles with mild nuclear atypia and an average of 2-3 mitotic figures per ten high-power fields. Multifocal nests of polygonal cells with abundant eosinophilic cytoplasm and round nuclei were seen within the spindle cells. Final pathology of the tumor revealed a cellular fibroma including Leydig cell hyperplasia.

Mucinous Lesions of the Breast.

Breast lesions associated with extracellular mucin production are uncommon and constitute a wide spectrum of lesions ranging from benign cyst to mucinous carcinoma. Intracytoplasmic mucin can be seen rarely in benign metaplasias but is a common finding in invasive and in situ carcinomas. In this article, we discuss the differential diagnosis of breast lesions associated with mucin production and other entities that show histologic changes that mimic mucin production.