Joon Seon Song

Global histone modification pattern associated with recurrence and disease‐free survival in non‐small cell lung cancer patients

Global histone modification patterns are presumed to establish epigenetic patterns of gene expression and determine the biology of the cell. In the present study, the global modification status of histone H3 and H4 was evaluated in 408 non‐small cell lung cancer (NSCLC) tissues by immunostaining. NSCLC showed variable staining scores for each antibody. Clinicopathological analyses demonstrated a positive correlation between weak nuclear staining for H3K9Ac (P < 0.001), H3K9TriMe (P= 0.001), H4K16Ac (P < 0.001) and tumor recurrence except H4K20 TriMe (P= 0.201). Staining scores of four different antibodies were not correlated with other clinicopathologic variables. Patients were further clustered according to histone modification patterns: acetylation dominant, methylation dominant, co‐dominant and modification‐negative. The acetylation‐dominant group (P= 0.009) and co‐dominant group exhibited less frequent lymph node metastasis (P= 0.050), recurrence (P= 0.002) and distant metastasis (P= 0.010). The acetylation‐dominant group showed better prognosis in survival analysis (P < 0.001, log‐rank), whereas methylation‐dominant and modification‐negative status was associated with poor prognosis. In conclusion, our data suggest that global histone H3 and H4 modification patterns are potential markers of tumor recurrence and disease‐free survival in NSCLC patients.

Finding and characterizing mammary analogue secretory carcinoma of the salivary gland.

Background A new tumor entity of the salivary glands, mammary analogue secretory carcinoma (MASC) with ETV6-NTRK3 translocation, has recently been proposed. MASC was originally diagnosed as adenocarcinoma, not otherwise specified (ANOS), or acinic cell carcinoma (AciCC) by the current World Health Organization classification. We aimed to identify MASC cases by molecular tests, and to characterize their clinical, histological, and immunohistochemical features. Methods Thirty cases of MASC candidates were selected after review of 196 salivary gland tumors, and subjected to break-apart ETV6 fluorescence in situ hybridization (FISH), and immunohistochemical study for S100 protein, gross cystic disease fluid protein 15, DOG1, estrogen receptor, and progesterone receptor. Results Valid FISH results were obtained in 23 cases, and 13 positive cases were retrieved. MASCs were histologically varied, and the most frequent features observed in 10 cases were low-grade papillary/cystic/glandular patterns, intraluminal secretory materials, ovoid/wrinkled nuclei, and relatively abundant granular eosinophilic cytoplasms, corresponding to papillary-cystic or follicular types of AciCC. All cases showed diffuse immunopositivity for S100 protein. Three cases developed recurrences, but all patients remained alive. Conclusions MASC could be a molecularly well-defined salivary gland neoplasm, encompassing some portions of AciCC and ANOS, but its histological spectrum and clinical implication require further investigation.

Cholangiocarcinoma arising in von Meyenburg complexes: Report of four cases

Although von Meyenburg complexes (VMC) are largely considered to be innocuous, neoplastic transformations have been described. The present report describes four cases of cholangiocarcinoma (CC) occurring on a background of VMC. The patients were all male and aged 69, 59, 68 and 75 years, respectively. While two patients were asymptomatic, the other two had a history of colon cancer. Radiologically the tumors measured 3, 4, 4.5 and 10 cm and were well enhanced from the arterial to delayed portal phase. Microscopically, the tumor consisted of multiple foci of characteristic VMC, and had a gradual transition from VMC to hyperplasia or dysplasia and well‐ to moderately differentiated adenocarcinomas. One patient had combined hepatocellular carcinoma (HCC) and CC, occurring in the high grade dysplastic nodule and VMC. On immunohistochemistry the epithelial cells of the VMC and CC were immunopositive for cytokeratin (CK) 7 in three patients, with another patient being focally positive only for CK19. The Ki‐67 labeling indices increased from the VMC to the dysplastic areas and then to the carcinomas. As a potentially precancerous lesion, VMC should be carefully followed up in terms of any size increases. Thus, biopsies are essential to determine any proliferative epithelial changes including dysplasia and malignant transformation.

Accuracy of Core Needle Biopsy Versus Fine Needle Aspiration Cytology for Diagnosing Salivary Gland Tumors

Background: Core needle biopsy is a relatively new technique used to diagnose salivary gland lesions, and its role in comparison with fine needle aspiration cytology needs to be refined. Methods: We compared the results of 228 ultrasound-guided core needle biopsy and 371 fine needle aspiration procedures performed on major salivary gland tumors with their postoperative histological diagnoses. Results: Core needle biopsy resulted in significantly higher sensitivity and more accurate tumor subtyping, especially for malignant tumors, than fine needle aspiration. No patient developed major complications after core needle biopsy. Conclusions: We recommend ultrasoundguided core needle biopsy as the primary diagnostic tool for the preoperative evaluation of patients with salivary gland lesions, especially when malignancy is suspected.

Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytology Diagnosis of Solid Pseudopapillary Neoplasm: Three Case Reports with Review of Literature

Solid pseudopapillary neoplasm of the pancreas (SPN) is relatively rare and it occurs almost exclusively in women. We recently experienced three cases of SPN diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). These three cases were two male and one female patient whose age was 29, 37, and 44 years old. Radiological diagnosis was pancreatic endocrine tumor (PEN) showing solid with a heterogenous echogenicity. EUS-FNA cytology specimens consisted of single cells and aggregates of uniform cells, forming microadenoid structures, branching, papillary clusters with delicate fibrovascular cores. In conclusion, a single diagnosis of SPN based on clinical and radiological findings would be risky because there is a possibility of it being misdiagnosed as PEN or other malignancies. An EUS-FNA is therefore essential for establishing the diagnosis. In addition, the pathologists should recognize the characteristic cytologic findings with immunoprofiles of SPN to prevent misdiagnosis of SPN.

Application of MDM2 Fluorescence In Situ Hybridization and Immunohistochemistry in Distinguishing Dedifferentiated Liposarcoma From Other High-grade Sarcomas.

Distinguishing dedifferentiated liposarcoma (DDLPS) from other high-grade spindle and pleomorphic sarcomas is important because of better prognosis in case of DDLPS. MDM2 amplification, a genetic abnormality of well-differentiated liposarcoma, is known to be present not only in DDLPS, but also in some other sarcomas. To differentiate DDLPS, we investigated MDM2 amplification and expression in high-grade spindle sarcomas. Eighty-five cases of nonlipogenic high-grade sarcomas, diagnosed between 2008 and 2011, were investigated. Tissue microarray, immunohistochemistry, and fluorescence in situ hybridization for MDM2 were performed. Forty-one of 85 cases (48.2%) showed MDM2 amplification and expression. Cases of MDM2 amplification were reclassified based on histology, immunophenotype, and clinical data. Thirty-nine of 41 cases, including those originally diagnosed as DDLPS (n=30), undifferentiated pleomorphic sarcoma (n=7), myxofibrosarcoma (n=1), and pleomorphic liposarcoma (n=1) could be reclassified as DDLPS. In addition, MDM2 immunohistochemistry and MDM2 fluorescence in situ hybridization showed an excellent correlation (P<0.001, sensitivity 92.7%, specificity 100%). MDM2 amplification and expression are potentially very useful in distinguishing between DDLPS and other undifferentiated high-grade spindle and pleomorphic sarcomas, even though a few other sarcomas also showed MDM2 amplification and expression.

Protuberant fibro-osseous lesions of the temporal bone: two additional case reports.

The most commonly encountered fibro-osseous lesions of the skull bone are fibrous dysplasia and ossifying fibroma. Two cases of a unique “protuberant fibro-osseous lesion of the temporal bone” were first described by Selesnick and colleagues in 1999, and 2 further cases were reported in 2010 under the name “Bullough lesion”. We recently found 2 new cases of this rare entity. Two Korean female patients aged 70 and 54 years presented with slow growing postauricular masses without pain or tenderness for 6 and 7 years, respectively. Computed tomography revealed a 2.9 cm calcified mass in the temporal bone of the first patient, and a 5.5 cm enhancing mass with internal cartilaginous matrix in the temporal bone of the second patient. Intramedullary or intracranial extension was not found in either case, and en bloc removals were performed. Microscopically, multiple round to oval osseous islands were scattered throughout the bland fibrous stroma in both cases. The osseous islands varied in size and were lamellar or woven, without osteoblastic rimming, and surrounded by fibroblastic bands. Neither patient has shown evidence of postoperative recurrence for 18 months. The location, histology, and clinical course of these 2 cases were identical to the 4 cases previously reported, although age and sex varied. The lesions were tested for the R201H mutation in the GNAS gene, which is present in fibrous dysplasia. No mutations were found, suggesting a different genetic background for these lesions.

Expression of human papillomavirus-related proteins and its clinical implication in tonsillar squamous cell carcinoma.

Background Human papillomavirus (HPV) is known to cause of oropharyngeal squamous cell carcinoma (SqCC). HPV positive SqCCs overexpress p16 and are associated with better survival. Several markers of cell cycles and apoptosis have been reported as a prognostic value. We examined the prognostic value of HPV status, p16, cyclin D1, and Bcl-2 in patients with tonsillar SqCC. Methods Tissue microarrays were constructed in 56 cases of tonsillar SqCC for which we performed an immunohistochemistry and an in situ hybridization (ISH) of the HPV. Results Of the 56 cases, 31 (55.3%) were positive for p16 and 20 (35.7%) were positive for HPV ISH. The expressions of p16, cyclin D1, and Bcl-2 were not correlated with the clinicopathologic variables including smoking status, differentiation and pT- and pN-stages. The HPV ISH positive group showed a better overall survival than the HPV negative group (p=0.04), and the p16 positive group showed a better disease free survival (DFS) than the negative group (p=0.016). Cox regression analysis showed that only p16 positivity was an independent prognostic factor for DFS (p=0.03; hazard ratio, 10.1). Conclusions Our results indicate that both p16 expression and HPV status are useful indicators for risk stratification in patients with tonsillar SqCC.

Mammary-Type Myofibroblastoma: A Report of Two Cases

Mammary-type myofibroblastoma (MFB) is a rare, benign spindle cell neoplasm occurring along the milkline, with extension from the mid-axilla to the medial groin. It is histologically and immunohistochemically identical to MFB of the breast and is part of a spectrum of lesions that includes spindle cell lipoma and cellular angiofibroma. Recently, we experienced two cases of mammary-type MFB involving male patients aged 30 and 58 years, respectively. The tumors were located in the right scrotal sac and in the right axilla. Wide excisions were performed. Microscopically, the masses were composed of haphazardly arranged, variably sized fascicles of bland spindle cells and were admixed with mature fat tissue. The spindle cells in both cases showed immunopositivity for desmin and CD34 and negativity for smooth muscle actin. Loss of retinoblastoma (RB)/13q14 loci is a characteristic genetic alteration of mammary-type MFB, and we identified loss of RB protein expression by immunohistochemical staining. We emphasize the importance of awareness of this rare neoplasm when a spindle cell neoplasm is accompanied by desmin immunopositivity. The second patient was alive without recurrence for 20 months, and the first patient had not been followed.

Clinicopathologic Features of the Non-cns Primary Ewing Sarcoma Family of Tumors in the Head and Neck Region

Ewing sarcoma family of tumor (ESFT) is a group of malignant neoplasms that affect children and young adults. Primary ESFT does not commonly arise from the head and neck region. This study aimed to elucidate the clinicopathologic characteristics of ESFT of the head and neck region except for central nervous system primitive neuroectodermal tumors. Among the 207 cases of ESFT of the bone and soft tissue, diagnosed at Asan Medical Center during a 20-year period, 25 (12.1%) involved the head and neck region. Of those, 21 were available for histologic, immunohistochemical, and molecular studies. EWSR1 rearrangement was detected in 19 cases by reverse transcriptase-polymerase chain reaction and/or fluorescence in situ hybridization. Primary sites included the cranial area (6 cases, 31.6%), sinonasal tract (6 cases, 31.6%), paraspinal space (4 cases, 21.0%), and other spaces (3 cases, 15.8%). The 5-year overall survival and disease-free survival rates for all cases were 69.7% and 33.6%, respectively. A large tumor size (>5 cm) correlated significantly with overall survival (P=0.009), but not with disease-free survival (P=0.210). Microscopically, 8 cases (42.1%) showed nested growth pattern. Clear and/or eosinophilic cytoplasm was observed in 68.4% cases. Immunopositivity for CD99, Friend leukaemia integration-1 (FLI-1), CD57, and caveloin-1 were detected in 100%, 88.9%, 83.3%, and 50% cases, respectively. ESFT in the head and neck region had a favorable prognosis and frequent atypical and epithelioid features. An awareness of these histologic and immunophenotypic characteristics will improve the diagnostic accuracy for head and neck round cell malignancies.