Trouble-makers in cytologic interpretation of the uterine cervix

The development and standardization of cytologic screening of the uterine cervix has dramatically decreased the prevalence of squamous cell carcinoma of the uterine cervix. Advances in the understanding of biology of human papillomavirus have contributed to upgrading the histologic diagnosis of the uterine cervix; however, cytologic screening that should triage those that need further management still poses several difficulties in interpretation. Cytologic features of high grade intraepithelial squamous lesion (HSIL) mimics including atrophy, immature metaplasia, and transitional metaplasia, and glandular lesion masquerades including tubal metaplasia and HSIL with glandular involvement are described with accentuation mainly on the differential points. When the cytologic features lie in a gray zone between the differentials, the most important key to the more accurate interpretation is sticking to the very basics of cytology; screening the background and cellular architecture, and then scrutinizing the nuclear and cytoplasmic details.

Digital Dermatopathology and Its Application to Mohs Micrographic Surgery

Digital pathology is being gradually adopted in hospitals due to technological advances. We propose that digital pathology can be used in Mohs micrographic surgery (Mohs surgery) to precisely check residual tumor cells in frozen tumor margin tissues. This would aid surgeons and pathologists in accurately recording tumor margins and give patients the benefit of shorter operation time.

Langerhans Cell Histiocytosis of the Thoracic Spine in an Adult Presenting as Thoracic Radiculopathy

A 35-year-old man complained of right truncal pain around T7-8 dermatomal distribution and on examination, T7-8 spinal tenderness was observed. Magnetic resonance imaging showed osteolytic mass in T8 vertebral body without structural lesions involving spinal nerve roots. Dermatomal somatosensory evoked potentials (DSEP) were helpful in diagnosis with thoracic radiculopathy. Finally, Langerhans cell histiocytosis was confirmed in bone biopsy. Thoracic radiculopathy can be caused by various etiologies including bone tumor and DSEP is useful supplementary tool for diagnosing thoracic radiculopathy.

Extremely Well-Differentiated Papillary Thyroid Carcinoma Resembling Adenomatous Hyperplasia Can Metastasize to the Skull: A Case Report

We describe herein histologic, immunohistochemical, and molecular findings and clinical manifestations of a rare case of an extremely well differentiated papillary thyroid carcinoma (EWD-PTC). Similarly, it is also difficult to diagnose follicular variant papillary thyroid carcinoma (FVPTC), whose diagnosis is still met with controversy. A recently reported entity of well-differentiated tumor of uncertain malignant potential (WDT-UMP) is added to the diagnostic spectrum harboring EWD-PTC and FVPTC. We report this case, because EWD-PTC is different from FVPTC in its papillary architecture, and also from WDT-UMP in its recurrence and metastatic pattern. These morphologically deceptive entities harbored diagnostic difficulties in the past because the diagnosis depended solely on histology. However, they are now diagnosed with more certainty by virtue of immunohistochemical and molecular studies. We experienced a case of EWD-PTC, which had been diagnosed as adenomatous hyperplasia 20 years ago and manifested recurrence with lymph node (LN) metastasis 7 years later. After another 7 years of follow-up, a new thyroid lesion had developed, diagnosed as FVPTC, with LN metastasis of EWD-PTC. One year later, the patient developed metastatic FVPTC in the skull. Immunohistochemically, the EWD-PTC was focally positive for CK19, negative for galectin-3, and focally negative for CD56. Molecular studies revealed BRAF-positivity and K-RAS negativity. The FVPTC in the left thyroid showed both BRAF and K-RAS negativity. In conclusion, EWD-PTC and FVPTC share similar histologic features, but they are different tumors with different molecular biologic and clinical manifestations. A large cohort of EWD-PTC should be included in further study.

The Intraoperative Immunohistochemical Staining of CD56 and CK19 Improves Surgical Decision for Thyroid Follicular Lesions

BACKGROUND: When differential diagnosis is difficult in thyroid follicular lesions with overlapping histological features, the immunohistochemical staining can help confirm the diagnosis. We aimed to evaluate the effectiveness of rapid immunohistochemical stains of CD56 and cytokeratin 19 on frozen sections of thyroid follicular lesion and explore the possible gains and limitations of the practice. METHODS: Eighty-six nodules of 79 patients whose intraoperative frozen sections were selected as the control group, and 53 nodules of 48 patients whose intraoperative frozen sections were subject to rapid immunohistochemistry were selected as the study group. RESULTS: Five nodules (6%) in the control group were diagnosed as follicular neoplasm and six nodules (7%) were deferred. In the study group, six nodules (11%) were follicular neoplasm and none were deferred. Three nodules (4%) in the control group showed diagnostic discrepancy between the frozen and permanent diagnoses, but none in the study group. The average turnaround time for the frozen diagnosis of the control group was 24 minutes, whereas it was 54 minutes for the study group. CONCLUSIONS: Intraoperative rapid immunohistochemical stains significantly decreased the diagnostic discrepancy in this study. Considering the adverse effects of indefinite frozen diagnosis or discrepancy with permanent diagnoses, the intraoperative rapid immunohistochemical stain can help to accurately diagnose and hence provide guidance to surgical treatment.

Male Infertility Associated with a Supernumerary Marker Chromosome

A marker chromosome (mar) is a structurally abnormal chromosome in which no part can be identified. The significance of a marker varies, depending on the material contained within the marker. Very few reports have been published of marker chromosomes associated with male infertility. Here, we report the case of an infertile man with a rare variant of a marker chromosome of a mos 47,XY,+mar[25]/46,XY[25] karyotype.

Successful delivery after conservative resectoscopic surgery in a patient with a uterine tumor resembling ovarian sex cord tumor with myometrial invasion

Uterine tumor resembling ovarian sex cord tumors (UTROSCT) is an extremely rare type of uterine stromal neoplasm that exhibits prominent sex cord-like differentiation. The clinical characteristics of a UTROSCT are not fully understood. Most reported cases of UTROSCT were treated by hysterectomy with or without bilateral salpingo-oophorectomy; however, a few cases have been treated by only tumor resection in patients who had a strong desire to preserve their fertility. We present a case of UTROSCT with myometrial invasion, which resulted in a successful delivery after the patient was treated by resectoscopic surgery and conservation of the uterus, and a brief review of the literature.

Cystic Nephroma: A Case Report and Comparing Literature Review with Mixed Epithelial and Stromal Tumor of Kidney

Cystic nephroma (CN) is a benign cystic neoplasm composed of mixed epithelial and stromal elements. Less than 200 cases have been reported. We had a patient, a 41-year-old woman, who had a huge typical CN. The patient was admitted for a right renal mass that was found incidentally. On laparaoscopic right nephrectomy, there was an encapsulated 7 cm multilocular cystic mass at the upper pole. Microscopically, the cystic wall was lined by a single layer of low cuboidal or hobnail epithelium without a solid area. The thin septa were composed of bland, ovarian type spindle cells. The main differential diagnoses were mixed epithelial and stromal tumor (MEST), low grade multilocular renal cell carcinoma, and tubulocystic carcinoma. The results of immunohistochemical staining were cytokeratin 7/19(+/+) and CD10(-) in lining epithelium, estrogen receptor/progesterone receptor(+/+) in stromal cells. After surgery, she was free of recurrence for 10 months. We report this rare case and compare it with other cystic renal tumors, especially MEST.

Cervical Cytologic Smears in Pap Solution vs ThinPrep: Smear Characteristics and Diagnostic Agreement

BACKGROUND: The Pap smear has brought about a dramatic improvement in the prevention of cervical cancer in women worldwide. In an effort to decrease the occasional false negatives in the Pap smear and further increase the screened population, ThinPrep Pap Test (TP), a fluid-based cytology collection method, has been developed. With preservation of claimed advantages of TP, we have developed a Pap test solution for manual preparatory process and compared our manually processed fluid-based Pap smear with TP to identify cytologic similarities and differences between the two methods. METHODS: Cervical swipes of 204 patients were prospectively collected in the 'Pap solution' and also in PreservCyt solution for TP. Diagnoses and smear characteristics were compared. RESULTS: The diagnoses of the paired smears agreed in 190 of the 204 cases (93.1%). The smear characteristics regarding overall cellularity and background cellularities were similar in the two methods and the stainability of the cells was virtually the same. CONCLUSIONS: The 'Pap solution' has similar performance characteristics as TP in many aspects. With its advantages of cost-effectiveness and easier preparatory process, the 'Pap solution' can match previously implemented thin layer preparation.

Comparison of CVF (Cyclophosphamide+Vinorelbine+5-Fluorouracil) and CMF (Cyclophosphamide+Methotrexate+5-Fluorouracil) Adjuvant Chemotherapy in Early Breast Cancer / 한국유방암학회지

PURPOSE: Our study aimed to evaluate the feasibility of adjuvant cyclophosphamide/vinorelbine/5-fluorourail (CVF) chemotherapy as an alternative to cyclophosphamide/methotrexate/5-fluorouracil (CMF) chemotherapy for treating early breast cancer. METHODS: One hundred and forty-nine patients were randomly assigned to CMF or CVF adjuvant chemotherapy for treating their early stage breast cancer between September 2000 and December 2007. The disease-free survival (DFS), the overall survival (OS), and the toxicity profiles of both groups were compared. RESULTS: Sixty-seven patients underwent CMF chemotherapy whereas 82 patients underwent CVF chemotherapy. The DFS and OS were 88 months (95% confidence interval [CI], 76-101 months) and 94 months (95% CI, 83-104 months), respectively for the CMF group, and 97 months (95% CI, 93-101 months), and 101 months (95% CI, 98-104 months), respectively for the CVF group. However, those survival gains of the CVF group were not statistically significant (p-value=0.069 for the DFS and 0.99 for the OS). The CVF group showed a favorable toxicity profile in terms of the grade 3/4 hematologic toxicities as compared to that of the CMF group. CONCLUSION: Clinical outcome of CVF chemotherapy was comparable to CMF with a favorable toxicity profiles. However, it is difficult to conclude the feasibility of CVF regimen because of small number of studied patients.

Lymphovascular Invasion and HER2/neu Amplification as Predictive Factors for Axillary Lymph Node Metastasis in Early Breast Cancer Patients / 한국유방암학회지

PURPOSE: Axillary lymph node metastasis (ALNM) can occur even in breast cancer smaller than 2 cm in size. This study was performed to investigate the clinicopathologic factors that affect node metastasis in T1 breast cancer. METHODS: We reviewed the medical record of 206 T1 breast cancer patients and we divided them into two groups according to the presence or absence of lymph node metastasis. We analyzed the association between ALNM and various clinicopathological predictive factors such as age, tumor size (T1a, T1b, T1c), multiplicity, the histologic grade, the nuclear grade, the presence of lymphovascular invasion (LVI), the estrogen and progesterone receptor status, an HER2/neu expression, the Ki-67 labeling index and the bcl-2 expression. RESULTS: One hundred and thirty-nine were the node negative group (T1N0) and the remaining 67 cases were allotted to the node positive group (T1N1-3). On the univariate analysis, age (p=0.011), LVI (p<0.001), histologic grade (p=0.019), HER2/neu (p<0.005), Ki-67 (p=0.012) and bcl-2 (p=0.026) were the statistically significant predictive factors related to node metastasis. But on the multivariate analysis, LVI (p<0.001) and HER2/neu (p=0.009) were the statistically significant factors related to node metastasis. CONCLUSION: LVI and HER2/neu overexpression were related to the increased incidence of ALNM in T1 breast cancer patients. LVI was the most predictive factor of ALNM.

A Case of Hantavirus Pulmonary Syndrome Mimicking Apalastic Anemia with Invasive Aspergillosis

Hantavirus is known to a causative agent of hemorrhagic fever with renal syndrome and it can cause hantavirus pulmonary syndrome, a rare disease in Korea. Hantavirus pulmonary syndrome is usually associated with pulmonary hemorrhage and fever. The common hematologic features of this syndrome are elevated hematocrit level, leukocytosis and thrombocytopenia. We report a case of hantavirus pulmonary syndrome with pancytopenia. This patient with severe neutropenia with pulmonary infiltration mimicked aplastic anemia with invasive aspergillosis.

Clinical Value of Ezrin Expression in Primary Osteosarcoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Ezrin is a membrane cytoskeletal linker protein and it is known to be associated with metastasis of primary osteosarcoma. The aim of this study is to determine the relationship between an ezrin expression and several key clinical parameters and to elucidate its potential prognostic value for patients with osteosarcoma. MATERIALS AND METHODS: Seventy patients with histologically confirmed osteosarcoma and who had no distant metastasis were enrolled between 1995 and 2005 at Yonsei Cancer Center, Severance Hospital, Korea. The clinical parameters were retrospectively reviewed and immunohistochemical staining (IHC) for ezrin was performed using the surgically resected specimens. RESULTS: Of the 70 tumor specimens, 39 (55.7%) revealed an ezrin expression. More of an osteoblastic histology and an elevated initial ALP level were observed in the ezrin positive patients than in the ezrin negative patients (p=0.008 and 0.001, respectively). The proportion of patients who favorably responded to neoadjuvant chemotherapy (> or =90% necrosis) was significantly higher in the group of ezrin positive patients than that in the group of ezrin negative patient (72.2% vs 45.2%, respectively, p=0.024). The ezrin positive patients showed more frequent recurrence than did the ezrin negative patients (64.1% vs 35.5%, respectively, p=0.017). The patients with an ezrin expression also demonstrated poorer survival than did those patients without ezrin expression (5-year EFS: 31.7% vs 61.3%, respectively, p=0.023, 5-year OS: 53.4% vs 71.0%, respectively, p=0.022). When comparing EFS according to both an ezrin expression and chemoresponsiveness, there were trends that the ezrin negative/chemoresponsive group showed the best 5-year EFS (71.4%), followed by the ezrin negative/chemoresistant group (52.9%), the ezrin positive/chemoresponsive group (38.1%) and the ezrin positive/chemoresistant group (13.6%). These trends were statistically significant (p=0.036). CONCLUSION: The expression of ezrin by IHC staining was found in 55.7% of the patients with metastasis-free osteosarcoma. Immunoreactivity to ezrin is a negative prognostic factor for survival for the patients suffering with osteosarcoma. Identifying an ezrin expression might offer a valuable piece of information when treating patients with primary osteosarcoma.

Osteopontin, CD44, and NFkappaB Expression in Gastric Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Osteopontin (OPN) binds to CD44 and nuclear factor-kappaB (NFkappaB) and OPN mediates tumorigenesis, invasion and metastasis, but the interrelationships between OPN, CD44 and NFkappaB are not fully understood, and especially in gastric carcinogenesis. We examined the expressions of OPN, CD44, and NFkappaB in untreated gastric adenocarcinomas. MATERIALS AND METHODS: The materials from 211 cases of gastric adenocarcinoma were immunostained for OPN, CD44 and NFkappaB by using a tissue microarray. The OPN mRNA expression was measured in 10 cases by performing real-time RT-PCR. RESULTS: The expression of OPN, CD44 and NFkappaB was noted in 61.7%, 11.4% and 26.6% of the adenocarcinoma tissues, respectively. No significant correlation was detected among the expressions of these proteins. The OPN protein expression was negatively correlated with angioinvasion (p<0.05) and patient survival (p<0.05), whereas the CD44 and NFkappaB protein expressions were not correlated with any of the clinicopathological factors we examined. The depth of invasion, lymph node status and perineural invasions were prognostic factors based on the Cox analysis. The OPN mRNA expression showed no significant difference between the adenocarcinoma and the paired normal mucosa on real-time RT-PCR. CONCLUSION: OPN may have a currently undetermined role in gastric carcinogenesis, and CD44 and NFkappaB may have minor roles in gastric adenocarcinoma.

Impact of Grade, Hormone Receptor, and HER-2 Status in Women with Breast Cancer on Response to Specific Chemotherapeutic Agents by in vitro Adenosine Triphosphate-based Chemotherapy Response Assay

This study was designed to assess whether histological and biological factors of breast cancer can predict chemoresponse to specific agents. Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) was employed to retrieve chemoresponse to 5-fluorouracil (5-FU), doxetaxel, doxorubicin, epirubicin, and paclitaxel in 49 patients. Tumors with high histologic and nuclear grade have higher response rate to doxorubicin (P<0.05) and palitaxel (P<0.05). Estrogen receptor (ER)-negative tumors respond well to doxorubicin (P=0.038), and progesterone receptor (PR)-negative tumors to 5-FU (P=0.039), doxetaxel (P=0.038), doxorubicin (P=0.000), epirubicin (P=0.010), and paclitaxel (P=0.003). Among the breast cancer subtypes determined by ER, PR, and HER-2 immunohistochemical stains, the HER-2+/ER- subtype has a higher response rate to doxorubicin (P=0.008). This in vitro result suggests that the combination of histologic and nuclear grade, hormone receptor, and HER-2 status can be a predictive factor of response to specific chemotherapy agents. Further in vivo study should be followed for clinical trials.

A Patient with Jejunal Mucinous Adenocarcinoma Metastatic to the Stomach Presenting with Submucosal Tumors in the Stomach and Jejunum / 대한소화기내시경학회지

The small bowel is the least common site for cancer to arise. Only approximately 1% of all gastrointestinal neoplasms arise in the small bowel. Mucinous adenocarcinoma is diagnosed when the amount of extracellular mucin in a tumor is over 50%. Because it is a very rare disease, there is little data available concerning its incidence, most common site of origin, and common sites of metastasis. There are no case reports describing primary mucinous adenocarcinoma of the jejunum in Korea. We report a case of jejunal mucinous adenocarcinoma metastatic to the stomach presenting as a submucosal tumor.

A case of primary transitional cell carcinoma of the ovary / 대한산부인과학회지

Primary ovarian transitional cell carcinoma (TCC) is extremely rare type of tumor and resembles transitional cell carcinoma of the bladder. Primary ovarian TCC has been classified as a different subtype from malignant Brenner tumor for it's histologic and clinical characteristics. It usually presents at an advanced stage .Though more aggressive than malignant Brenner tumor, it shows more favorable prognosis because of better response to the chemotherapy than other epithelial ovarian carcinomas. We experienced a case of primary ovarian transitional cell carcinoma in a premenopausal woman who underwent staging operation and chemotherapeutic treatment, and herein report the case with a brief review of related literatures.

Ki-1 Positive Extranodal NK/T Cell Lymphoma, Nasal Type, Mistaken as Dermatomyositis: A Case Report and Literature Review

We report a case of a 38-year-old male with extranodal NK/T-cell lymphoma, nasal type, showing unusual clinical and pathological features. The patient was admitted for soft tissue swelling and tenderness in both legs. The patient had been treated intermittently 8 months prior for repeated muco-cutaneous ulcers. A muscle biopsy showed medium-sized atypical lymphoid cells with bizarre nuclei and plump cytoplasm, infiltrating to the skeletal muscle fibers with angiocentricity. The immunoresults were Ki-1+, CD56+, cytoplasmic CD3+, with EBV-in situ hybridization +. The patient rapidly deteriorated and died of sepsis and respiratory failure shortly after initiation of low-dose chemotherapy. A careful review of previous biopsies revealed scarce atypical lymphoid cells around vessels with similar immunoprofiles without the presence of Ki-1 positive cells. This case emphasizes that an extranodal NK/T-cell lymphoma may have a dermatomyositis-like diffuse presentation. Ki-1 co-expression can be an unexpected event in a process of the disease course; however, this should be validated with future studies.

Correlation between C-MYC and HER2 Amplification in Non-selected Breast Cancers / 한국유방암학회지

PURPOSE: c-myc and HER2 have been reported be amplified in 20% to 30% of clinical breast cancers and appears to be related with poor clinical outcome. The relationship between amplification of c-myc and HER2 and other clinical and biological characteristics of the breast cancers, including clinical outcome, are described. METHODS: c-myc and HER2 amplification were analyzed on 225 consecutive non-selected breast cancers by fluorescence in situ hybridization using tissue microarray technology. RESULTS: c-myc was amplified in 33 cases (15.4%) and HER2 was amplified in 49 cases (23.3%). c-myc amplification was significantly increased with HER2 amplification (p<0.001) and closely linked with cell proliferative activity measured by Ki67 labeling index (p=0.010). In univariate survival analysis, lymph node status, tumor size, and histologic grade of the tumors were significant prognostic factors. However, lymph node status was the only significant prognostic factor for predicting patient survival in multivariate analysis. Patient survival was not different according to c-myc amplification status and c-myc amplification showed no significant correlation with clinco-pathologic parameters of the tumors. CONCLUSION: A strong correlation between c-myc and HER2 amplifications, and cell proliferative activity indicate a biologic link between c-myc and HER2 in breast cancer.

RET/PTC and CK19 Expression in Papillary Thyroid Carcinoma and Its Clinicopathologic Correlation

Recently, the rearrangement of RET proto-oncogene has been reported to be the most common genetic change in papillary thyroid carcinoma (PTC). However, its prevalence has been reported variably and its relation to clinical outcome has been controversial. The characteristic nuclear features of PTC usually render the diagnosis, but problem arises with equivocal cytologic features that are present focally. Although there remains some controversy, CK19 has been reported to be a useful ancillary tool for diagnosis of PTC. To evaluate the expression rate of RET/PTC rearrangement and CK19 in PTCs in a Korean population, we studied 115 papillary thyroid carcinomas in 3 mm-core tissue microarray based immunohistochemical analysis. The prevalence of Ret protein expression was 62.6% and the CK19 immunoreactivity was 80.9%. There was no statistically significant asso-ciation between the Ret positivity and CK19 immunoreactivity, although the percent agreement of the two was relatively high. The clinicopathological variables did not correlate with the expression of Ret. In conclusion, the prevalence of Ret protein expression and its clinicopathological implications in a Korean population are not much different from those reported in previous studies. However, its detection via immunohistochemistry can be a useful diagnostic tool for diagnosing papillary thyroid carcinoma in conjunction with CK19.