Response Evaluation to Neoadjuvant Chemotherapy in Breast Cancer Patients: Sequential Dynamic Contrast-Enhanced MRI Using Computer-Aided Detection

Purpose@#We evaluated whether there is an association between sequential changes in kinetic profiles by computer-aided detection (CAD) during neoadjuvant chemotherapy (NAC) and pathologic complete response (pCR) and residual cancer burden (RCB) in dynamic contrast-enhanced MRI (DCE-MRI) of patients with invasive breast cancer. @*Materials and Methods@#This retrospective study involved 51 patients (median age, 48 years; range, 33–60 years) who underwent pre-, interim-, and post-NAC DCE-MRIs at 3 T. The tumor size and CAD-generated kinetic profiles (peak enhancement and delayed enhancement [persistent, plateau, and washout] components) were measured. Percentage changes in pre- and interim-NAC (ΔMRI value1) and pre- and post-NAC (ΔMRI value2) were compared between pCR and non-pCR cases, and according to RCB. Receiver operating characteristic curve analysis was performed to evaluate the association between pCR and MRI parameters (including CAD-generated kinetic profiles). @*Results@#The pCR rate was 19.6% (10/51). There were statistically significant differences in Δtumor size2 (p < 0.01), Δpeak enhancement2 (p = 0.01), Δpersistent2 (p = 0.01), Δplateau2 (p = 0.02), and Δwashout2 (p = 0.03) between pCR and non-pCR. ΔTumor size2 provided very good diagnostic accuracy for pCR (cut-off, -90%; area under the curve, 0.88). There were differences in Δtumor size2, Δpeak enhancement2, Δplateau2, and Δwashout2 between RCB classes (p < 0.01). @*Conclusion@#DCE-MRI using CAD has the potential for predicting pCR and RCB classes.

A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification

Background@#Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification. @*Methods@#Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier). @*Results@#On WHO classification, H&E staining exhibited ‘fair agreement’ (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems. @*Conclusions@#Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Histologically confirmed distant metastatic urothelial carcinoma from the urinary bladder: a retrospective review of one institution’s 20-year experience

Background@#Urothelial carcinoma (UC) accounts for roughly 90% of bladder cancer, and has a high propensity for diverse differentiation. Recently, certain histologic variants of UC have been recognized to be associated with unfavorable clinical outcomes. Several UC studies have also suggested that tumor budding is a poor prognostic marker. Distant metastasis of UC after radical cystectomy is not uncommon. However, these metastatic lesions are not routinely confirmed with histology. @*Methods@#We investigated the histopathologic features of 13 cases of UC with biopsy-proven distant metastases, with a special emphasis on histologic variants and tumor budding. @*Results@#Lymph nodes (6/13, 46%) were the most common metastatic sites, followed by the lung (4/13, 31%), liver (4/13, 31%), and the adrenal gland (2/13, 15%). The histologic variants including squamous (n=1), micropapillary (n=4), and plasmacytoid (n=1) variants in five cases of UC. Most histologic variants (4/5, 80%) of primary UCs appeared in the metastatic lesions. In contrast, high-grade tumor budding was detected in six cases (46%), including one case of non-muscle invasive UC. Our study demonstrates that histologic variants are not uncommonly detected in distant metastatic UCs. Most histologic variants seen in primary UCs persist in the distant metastatic lesions. In addition, high-grade tumor budding, which occurs frequently in primary tumors, may contribute to the development of distant metastasis. @*Conclusions@#Therefore, assessing the presence or absence of histologic variants and tumor budding in UCs of the urinary bladder, even in non-muscle invasive UCs, may be useful to predict distant metastasis.

Double cocktail immunostains with high molecular weight cytokeratin and GATA-3: useful stain to discriminate in situ involvement of prostatic ducts or acini from stromal invasion by urothelial carcinoma in the prostate

Background@#Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate. @*Methods@#Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion. @*Results@#In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised. @*Conclusions@#Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.

Human Epidermal Growth Factor Receptor 2-Subtype Invasive Ductal Carcinoma Recurring as Basal-Human Epidermal Growth Factor Receptor 2-Subtype Squamous Cell Carcinoma / 한국유방암학회지

Squamous cell carcinoma of the breast and its subtype, basal-human epidermal growth factor receptor 2 (HER2) phenotype, are very rare. Herein, we report a patient who developed recurrence of squamous cell carcinoma of the breast with basal-HER2 subtype 6 years after the initial diagnosis of invasive ductal carcinoma of the HER2 subtype. To the best of our knowledge, recurrence of invasive ductal carcinoma in the form of metaplastic squamous cell carcinoma of basal-HER2 subtype has not been reported previously. We present a pathological perspective of our experience.

14-3-3ζ Overexpression is Associated with Poor Prognosis in Ovarian Cancer

PURPOSE: 14-3-3ζ regulates cell signaling, cell cycle progression, and apoptosis, and its overexpression is associated with disease recurrence and poor clinical outcomes in some solid tumors. However, its clinicopathological role in ovarian cancer is unknown. Our goal was to investigate whether 14-3-3ζ is associated with ovarian cancer prognosis. MATERIALS AND METHODS: We examined 14-3-3ζ expression by immunohistochemistry in ovarian cancer tissues obtained from 88 ovarian cancer patients. The examined tissues were of various histologies and stages. 14-3-3ζ expression was also analyzed by western blot in seven ovarian cancer cell lines and a primary ovary epithelial cell line. Cell viability was measured using an MTS-based assay following cisplatin treatment. RESULTS: Among the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3ζ expression, and 14-3-3ζ overexpression was positively correlated with more advanced pathologic stages and grades. 14-3-3ζ overexpression was also significantly associated with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14-3-3ζ expression group, but not reached in the low 14-3-3ζ expression group (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3ζ by RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin-induced cell death. CONCLUSION: 14-3-3ζ overexpression might be a potential prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3ζ could be a therapeutic option that enhances the antitumor activity of cisplatin.

Comparison of Unsatisfactory Samples from Conventional Smear versus Liquid-Based Cytology in Uterine Cervical Cancer Screening Test

BACKGROUND: Cervical cytology for uterine cervical cancer screening has transitioned from conventional smear (CS) to liquid-based cytology (LBC), which has many advantages. The aim of this study was to compare the proportion of unsatisfactory specimens from CS versus LBC at multiple institutions including general hospitals and commercial laboratories. METHODS: Each participating institution provided a minimum of 500 Papanicolaou (Pap) test results for analysis. Pap tests were classified according to the participating institution (commercial laboratory or general hospital) and the processing method (CS, ThinPrep, SurePath, or CellPrep). The causes of unsatisfactory results were classified as technical problems, scant cellularity, or complete obscuring factors. RESULTS: A total of 38,956 Pap test results from eight general hospitals and three commercial laboratories were analyzed. The mean unsatisfactory rate of LBC was significantly lower than that of CS (1.26% and 3.31%, p = .018). In the LBC method, samples from general hospitals had lower unsatisfactory rates than those from commercial laboratories (0.65% vs 2.89%, p = .006). The reasons for unsatisfactory results were heterogeneous in CS. On the other hand, 66.2% of unsatisfactory results in LBC were due to the scant cellularity. CONCLUSIONS: Unsatisfactory rate of cervical cancer screening test results varies according to the institution and the processing method. LBC has a significantly lower unsatisfactory rate than CS.

Value of imaging study in predicting pelvic lymph node metastases of uterine cervical cancer

PURPOSE: To evaluate the diagnostic accuracy of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) in predicting pelvic lymph node (LN) metastases in patients with cervical cancer. MATERIALS AND METHODS: From January 2009 to March 2015, 114 patients with FIGO stage IA1-IIB uterine cervical cancer who underwent hysterectomy with pelvic lymphadenectomy and took CT, MRI, and PET/CT before surgery were enrolled in this study. The criteria for LN metastases were a LN diameter ≥1.0 cm and/or the presence of central necrosis on CT, a LN diameter ≥1.0 cm on MRI, and a focally increased FDG uptake on PET/CT. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for pelvic LN metastases were estimated. RESULTS: The sensitivity, specificity, PPV, NPV, and accuracy for detection of pelvic LN metastases were 51.4%, 85.9%, 41.3%, 90.1%, and 80.3% for CT; 24.3%, 96.3%, 56.3%, 86.8%, and 84.6% for MRI; and 48.6%, 89.5%, 47.4%, 90.0%, and 82.9% for PET/CT, respectively. The sensitivity of PET/CT and CT was higher than that of MRI (p=0.004 and p= 0.013, respectively). The specificity of MRI was higher than those of PET/CT and CT (p=0.002 and p=0.001, respectively). The difference of specificity between PET/CT and CT was not statistically significant (p=0.167). CONCLUSION: These results indicate that preoperative CT, MRI, and PET/CT showed low to moderate sensitivity and PPV, and moderate to high specificity, NPV, and accuracy. More efforts are necessary to improve sensitivity of imaging modalities in order to predict pelvic LN metastases.

Langerhans Cell Histiocytosis of the Thoracic Spine in an Adult

We report a case of a 45-year-old man with a complaint of both leg weakness and hypoesthesia. Radiological evaluation revealed an osteolytic lesion of the ninth thoracic vertebra. The patient underwent posterior corpectomy with total excision of the tumor, mesh cage insertion with posterior screw fixation and subsequent radiotherapy. Histology confirmed the diagnosis of Langerhans cell histiocytosis (LCH). This case report presents the diagnostic work-up, histopathological evaluation, and the treatment procedures of rare LCH in the thoracic spine.

Lymphedema Associated With Primary Amyloidosis: A Case Study

We reported on a 60-year-old man presenting lymphedema of both lower extremities and scrotum for 3 years with unknown cause. We took a computed tomography scan of the lower extremities as a follow-up. There were diffuse subcutaneous edema in both lower extremities and multiple enlarged lymph nodes along the para-aortic and bilateral inguinal areas. For further evaluation, biopsy of an enlarged inguinal lymph node was taken, yielding a diagnosis of primary amyloidosis. A treatment of chemotherapy for amyloidosis was recommended for him. To our knowledge, this is the first report of lymphedema presenting with primary amyloidosis in Asia. This case suggests that primary amyloidosis could be one of the differential diagnoses in patients with lymphedema in the lower extremities.

A Case of Cutaneous Protothecosis in an Immunocompetent Patient

No abstract available.

Outcome of Localized Granulomatosis with Polyangiitis: A Case Study

OBJECTIVE: A substantial portion of granulomatosis with polyangiitis (GPA) patients present with localized disease limited to the upper respiratory tract, however; disease spectrum and prognosis of these patients are unclear. The aim of this study is to describe the clinical characteristics and outcome of patients with localized GPA. METHODS: This was a retrospective descriptive case series of patients with a biopsy proven localized GPA presenting to a single tertiary rheumatology service between January 1995 and September 2015. RESULTS: A total of 5 patients, median age 56 years (range 48 to 59 years) at diagnosis and 80% female, were identified. The median follow-up period was 42 months (range 15 to 62 months). Diagnosis was delayed with median time to diagnosis of 12 months (range 3 to 36 months), and patients underwent 1-3 ear, nose, and throat surgeries during the period of diagnostic delay. Sinusitis was the most frequent symptom in all patients, followed by otomastoiditis with cranial nerve palsies (n=2) and orbital mass (n=1). Antineutrophil cytoplasmic antibody (ANCA) was positive initially in 2/5 patients (40%). Two patients with otomastoiditis and cranial nerve palsies progressed to systemic disease with ANCA positive conversion. These two cases along with a case with orbital mass were refractory to standard treatment of cyclophosphamide with glucocorticoids requiring rituximab treatment. CONCLUSION: Patients with localized GPA may progress to systemic disease over the disease course, and may have aggressive disease refractory to standard treatment. Close monitoring for systemic symptoms and repeated ANCA testing is required in patients with localized GPA.

Analysis of Mutations in Epidermal Growth Factor Receptor Gene in Korean Patients with Non-small Cell Lung Cancer: Summary of a Nationwide Survey

BACKGROUND: Analysis of mutations in the epidermal growth factor receptor gene (EGFR) is important for predicting response to EGFR tyrosine kinase inhibitors. The overall rate of EGFR mutations in Korean patients is variable. To obtain comprehensive data on the status of EGFR mutations in Korean patients with lung cancer, the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists initiated a nationwide survey. METHODS: We obtained 1,753 reports on EGFR mutations in patients with lung cancer from 15 hospitals between January and December 2009. We compared EGFR mutations with patient age, sex, history of smoking, histologic diagnosis, specimen type, procurement site, tumor cell dissection, and laboratory status. RESULTS: The overall EGFR mutation rate was 34.3% in patients with non-small cell lung cancer (NSCLC) and 43.3% in patients with adenocarcinoma. EGFR mutation rate was significantly higher in women, never smokers, patients with adenocarcinoma, and patients who had undergone excisional biopsy. EGFR mutation rates did not differ with respect to patient age or procurement site among patients with NSCLC. CONCLUSIONS: EGFR mutation rates and statuses were similar to those in published data from other East Asian countries.

Rectus Abdominis Muscle Tuberculosis Involving Lung and Endometrium / 이화의대지

Extrapulmonary tuberculosis usually involves the pleura, central nervous system, lymphatic system, genitourinary system and bone with joint. There are few reports about pulmonary tuberculosis involving the endometrium and muscle. A 32-year-old woman who had intact immunity visited hospital due to menorrhagia, and was diagnosed with endometrial tuberculosis. The patient also had a painless abdominal mass about for 1 year before she came to the hospital. She was diagnosed with rectus abdominis muscle tuberculosis, endometrial tuberculosis, and pulmonary tuberculosis at the same time. We report a case of endometrial tuberculosis accompanied with rectus abdominis muscle and pulmonary tuberculosis in a non-immunosuppressed person.

Two Cases of Bronchopulmonary Dysplasia of Similar Appearance in Adult Monozygotic Twin: Pathology and Computed Tomographic Findings / 결핵및호흡기질환

Bronchopulmonary dysplasia (BPD) is related to decreased lung function throughout life. However, the pathology and radiology pattern of BPD of adults are not documented well yet. In this case report, we present BPD case of an adult monozygotic twin showing nearly identical lesions on chest computed tomography (CT). CT images showed mixed areas of ground-glass and reticular opacities in both lungs. They had common histories of pneumonias requiring mechanical ventilations in period of infants. Pulmonary function test of one patient showed a pulmonary insufficiency with airway obstruction. Pathologic findings showed bronchiolar hyperplasia and peribronchiolar fibrosis which was similar to classic BPD patients. Our twin case report might help provide distinguishing pathology and radiology pattern of an adult pulmonary sequelaes of BPD. It might be reasonable to make close follow-up for BPD patients to evaluate the long-term outcomes of BPD survivors.

Zonal Difference and Prognostic Significance of Foxp3 Regulatory T Cell Infiltration in Breast Cancer / 한국유방암학회지

PURPOSE: Forkhead box P3 (Foxp3) is known as the most specific marker for regulatory T lymphocytes, which play an important role in immune tolerance to disturb antitumor immunity. The present study aimed to investigate the prognostic significance of Foxp3 regulatory T lymphocyte (Foxp3 Treg) infiltration in breast cancer. METHODS: Immunohistochemical studies with Foxp3, CD4, and CD8 were performed on representative full tissue sections from 143 patients with invasive ductal carcinoma, not otherwise specified. Foxp3 Treg infiltration and the ratios between Foxp3 Treg and CD4 or CD8 T cells were separately analyzed for the tumor bed and tumor periphery to evaluate their association with different clinicopathological parameters and patients' outcome. RESULTS: The tumor periphery was considerably more densely infiltrated by Foxp3 Treg, CD4, and CD8 T cells than the tumor bed. Unfavorable clinicopathological parameters (a Ki-67 labeling index of > or =14%, a worse histologic grade, a worse nuclear grade, hormone receptor negativity, human epidermal growth factor receptor 2 positivity, and tumor recurrence) were associated with increased Foxp3 Treg infiltration and a high ratio between Foxp3 Treg and CD4/CD8 T cells. In the tumor periphery, as Foxp3 Treg infiltration and the Foxp3 Treg/CD8 ratio increased, patients' 5-year disease-free survival rate decreased. CONCLUSION: The infiltration densities of Foxp3 Treg, CD4, and CD8 T cells were markedly different between the tumor bed and periphery. Besides the absolute count of Foxp3 Treg, the ratio between Foxp3 Treg and effector T cells was a significant prognostic factor in breast cancer.

Correlation between the molecular subtype of breast cancer and the in vitro adenosine triphosphate-based chemosensitivity assay / 대한외과학회지

PURPOSE: The empirical use of a chemotherapy regimen shows different results in individual breast cancer patient treatment. Recent studies showed the effectiveness of the adenosine triphosphate-based chemotherapy response assay (ATP-CRA). However, little is known about the correlation between chemosensitivity and breast cancer molecular subtypes. Therefore, we investigated whether the result of ATP-CRA is associated with a molecular subtype of breast cancer. METHODS: Two hundred eighty-seven patients diagnosed with breast cancer and receiving ATP-CRA at Mokdong Hospital, Ewha Womans University between September 2007 and December 2010 were enrolled in this study. Hormone receptor status, HER2/neu expression, and results of chemosensitivity tests of the patients was analyzed. RESULTS: In all of four subtypes, the combination of two agents showed significant higher mean cell death rate than a single agent. Within the breast cancer cell lines in this study, the range of chemosensitivity response was very wide and varied for each patient. For this reason, the molecular subtype of breast cancer is inconclusive in choosing an effective chemotherapeutic agent and in vitro chemosensitivity test, prior to therapy, could be a useful method for planning chemotherapy for each patient. CONCLUSION: Chemosensitivity response to anticancer agents was found to vary depending on the individual breast cancer patients. The molecular subtype of breast cancer is inconclusive to choose the effective chemotherapeutic agent and the in vitro chemosensitivity test, prior to therapy, could be more useful for planning chemotherapy for each patient.

Isolated Post-Transplantation Lymphoproliferative Disease Involving the Breast and Axilla as Peripheral T-cell Lymphoma

Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent serious complications following immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually associated with Epstein Barr Virus infection. Moreover, to our knowledge, isolated T-cell PTLD involving the breast is extremely rare and this condition has never been reported previously in the literature. Herein, we report a rare case of isolated T-cell PTLD of the breast that occurred after a patient had been treated for allogeneic peripheral blood stem cell transplantation due to acute myeloblastic leukemia.

A case of membranoproliferative glomerulonephritis associated with metastatic colon cancer

No abstract available.

Amiodarone-Induced Pulmonary Toxicity: Percutaneous Needle Aspiration Biopsy and Ultrastructural Findings / 이화의대지

Amiodarone has been widely used for supraventricular and ventricular arrhythmias and many patients benefit from its effectiveness in treating potentially life-threatening arrhythmias. However, this drug can cause multi-organ toxicity, including amiodarone-induced pulmonary toxicity (APT). Not only does amiodarone have a long half-life but also is lipophilic and therefore can easily accumulate in tissues. Hence, it is difficult to monitor therapeutic levels and side effects, making it difficult to predict toxicities. In this case, we describe multi-organ complications secondary to amiodarone use, especially APT combined with pneumonia with atypical pathogens and pulmonary hemorrhage. The patient reached a high cumulative dose of amiodarone despite a low maintenance dose of amiodarone. This case highlights an unusual presentation of APT with multi-organ toxicity and we review articles regarding the association between the cumulative dose of amiodarone and amiodarone-induced toxicities.