Favorable clinical efficacy of cytotoxic chemotherapy in patients with progressive desmoid tumors: a retrospective real-world study.

BACKGROUND: The real-world evidence about the efficacy of cytotoxic chemotherapy in desmoid tumors is still limited. We investigated the efficacy of chemotherapy in the treatment of recurrent or progressive desmoid tumors. METHODS: The patients with desmoid tumors who had received cytotoxic chemotherapy between November 2007 and June 2020 in two tertiary hospitals in Korea were reviewed. RESULTS: A total of 25 patients were included in the analysis. The most common primary tumor site was the intra-abdominal or pelvic cavity (56%), followed by the trunk and abdominal wall (24%), extremities (16%), and head and neck (4%). Sixty percent of the patients had familial adenomatous polyposis and 76% received doxorubicin plus dacarbazine. The objective response rate and disease control rate was 64% (95% confidence interval [CI]: 40.7-82.8) and 96% (95% CI: 77.2-99.9), respectively. With the median follow-up time of 55 months (95% CI: 41.0-68.2), the 3-year PFS rate was 65% (95% CI: 41.1-80.5), and the 3-year OS rate was 89% (95% CI: 63.8-97.3). Grade 3 or 4 hematologic adverse events were reported in 14 patients, all of which were manageable. CONCLUSION: Our real-world evidence suggests that doxorubicin-based cytotoxic chemotherapy can be an effective treatment option for recurrent and progressive desmoid tumors with respect to favorable clinical outcomes.

Prognostic Significance of Tumor-Infiltrating Lymphocytes and High-Risk Human Papillomavirus in Ocular Sebaceous Carcinoma: A Comprehensive Analysis.

High-risk human papillomavirus (hrHPV) and tumor-infiltrating lymphocytes (TILs) are known to have prognostic significance in oropharyngeal squamous cell carcinoma. However, their significance in ocular sebaceous carcinoma (OSC) remains unverified because of the rarity of the condition. This study aimed to investigate the association between clinicopathologic features, biomarkers, and hrHPV infection and their potential to predict prognosis in OSC patients. We analyzed the clinicopathologic features of 81 OSC patients from Asan Medical Center between 2000 and 2022. Seventeen biomarkers and hrHPV were examined using immunohistochemistry and DNA in situ hybridization on tissue microarray cores. hrHPV was identified in 31 cases (38.3%). Univariate analysis revealed that hrHPV infection was associated with comedonecrosis (P = .032), high Ki-67 labeling index (≥30%, P = .042), lower expression of E-cadherin (P = .033), and loss of expression of zinc finger protein 750 (P = .023). Multivariate analysis revealed that loss of expression of zinc finger protein 750 (P = .026) remained an independently associated factor for hrHPV. Progression-free survival analysis was performed on 28 patients who were continuously observed for more than 5 years. During a median follow-up duration of 86 months, recurrence or metastasis developed in 14 patients (50%) within the survival cohort, occurring at a median time of 48 months after excision. Univariate analysis indicated that recurrence or metastasis was associated with tumor size (P = .010), high TILs (≥10%; P = .025), lymphovascular invasion (P = 0.043), site of origin (P = .025), and high expression of bcl-2-associated athanogene 3 (P = .039). Multivariate analysis demonstrated that high TILs (P = .017) and site of origin (P = .025) were independent prognostic factors. The prognosis of OSC was hrHPV-independent, and a better prognosis was associated with the site of origin in the order of the gland of Zeis, meibomian gland, and multicentric site, as well as with high TILs.

P16 expression and presence of lymphoid stroma are correlated with good prognosis in mucoepidermoid carcinoma of the head and neck.

BACKGROUND: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. This study was designed to identify valuable prognosticator in MEC. METHODS: Histopathologic analysis, immunohistochemistry, and in situ hybridization were performed on 128 carcinomas diagnosed as MEC of the head and neck. RESULTS: Expression of p16 was found in 96 cases (76%) of MEC. Lymphoid stroma was identified in 63 cases (49%). There was a significant correlation between loss of p16 expression and absence of lymphoid stroma. Expression of p16 was significantly associated with better clinicopathologic features. Lymphoid stroma was significantly associated with lower histologic grade. Overall survival (OS) was significantly longer in cases expressing p16 (P = 0.00096) and lymphoid stroma cases (P = 0.0023). Multivariate analysis revealed loss of p16 expression as negative prognosticators for OS. CONCLUSION: Our data showed p16 expression and the presence of lymphoid stroma were significantly associated with good clinical outcomes. Testing for these factors could lead to better prognostication and treatment of patients with MEC.

Salivary Gland Neoplasms With a Unique Trabecular Histology and MAML2 Translocation : A Trabecular Variant of a Mucoepidermoid Carcinoma.

Mucoepidermoid carcinomas (MECs) are the most common salivary gland malignancy and have a diverse histology. Many histologic variants of MEC have now been confirmed with characteristic molecular alterations involving CRTC1::MAML2 or CRTC1::MAML3 translocations. We here report a series of 7 trabecular variants of MEC which showed a predominant trabecular or nested pattern with either focal glandular differentiation or clear cell change and keloid-like fibrosis in the background. In addition, these tumors were either negative or showed only focal positivity for p63. Such features are not characteristic of known disease entities and resulted in an initial misdiagnosis of adenocarcinoma, not otherwise specified, or low-grade to intermediate-grade MEC with uncertainty. The patients' ages in our cohort ranged from 26 to 55 years with a female predominance (5/7). The tumors were located in the parotid gland (n=3), base of tongue (n=2), hard palate (n=1), and parapharyngeal space (n=1), with a median size of 1.5 cm. All 7 cases showed an MAML2 split pattern on fluorescence in situ hybridization analysis, and both RNA and whole-genome sequencing presented CRTC1::MAML2 translocation. All 7 cases showed a solid-predominant histology, and 3 cases displayed extracapsular extension. There were no other signs of high-grade histology and no recurrences or deaths occurred over a follow-up period of up to 79 months. We thus propose a unique trabecular variant of MEC that has atypical histologic and immunohistochemical features.

Predictive modelling for the diagnosis of oral and laryngeal premalignant and malignant lesions using p53 and Ki-67 expression.

Oral and laryngeal epithelial lesions are currently diagnosed using histological criteria based on the World Health Organization (WHO) classification, which can cause interobserver variability. An integrated diagnostic approach based on immunohistochemistry (IHC) would aid in the interpretation of ambiguous histological findings of epithelial lesions. In the present study, IHC was used to evaluate the expression of p53 and Ki-67 in 114 cases of oral and laryngeal epithelial lesions in 104 patients. Logistic regression analysis and decision tree algorithm were employed to develop a scoring system and predictive model for differentiating the epithelial lesions. Cohen's kappa coefficient was used to evaluate interobserver variability, and next-generation sequencing (NGS) and IHC were used to compare TP53 mutation and p53 expression patterns. Two expression patterns for p53, namely, diffuse expression type (pattern HI) and null type (pattern LS), and the pattern HI for Ki-67 were significantly associated with high-grade dysplasia (HGD) or squamous cell carcinoma (SqCC). With an accuracy and area under the receiver operating characteristic curve (AUC) of 84.6% and 0.85, respectively, the scoring system based on p53 and Ki-67 expression patterns classified epithelial lesions into two types: non-dysplasia (ND) or low-grade dysplasia (LGD) and SqCC or HGD. The decision tree model constructed using the p53 and Ki-67 expression patterns classified epithelial lesions into ND, LGD, and group 2, including HGD or SqCC, with an accuracy and AUC of 75% and 0.87, respectively. The integrated diagnosis had a better correlation with near perfect agreement (weighted kappa 0.92, unweighted kappa 0.88). The patterns HI and LS for p53 were confirmed to be correlated with missense mutations and nonsense/frameshift mutations, respectively. A predictive model for diagnosis was developed based on the correlation between TP53 mutation and p53 expression patterns. These results indicate that the scoring system based on p53 and Ki-67 expression patterns can differentiate epithelial lesions, especially in cases when the morphological features are ambiguous.

Primary cardiac sarcomas: A clinicopathologic study in a single institution with 25 years of experience with an emphasis on MDM2 expression and adjuvant therapy for prognosis.

BACKGROUND: Primary cardiac sarcomas are rare and their clinicopathologic features are heterogeneous. Among them, particularly intimal sarcoma is a diagnostic challenge due to nonspecific histologic features. Recently, MDM2 amplification reported to be a characteristic genetic event in the intimal sarcoma. In this study, we aimed to identify the types and incidence of primary cardiac sarcomas that occurred over 25 years in tertiary medical institutions, and to find clinicopatholgical significance through reclassification of diagnoses using additional immunohistochemistry (IHC). METHODS: We reviewed the primary cardiac sarcoma cases between January 1993 and June 2018 at Asan Medical Center, South Korea, with their clinicopathologic findings, and reclassified the subtypes, especially using IHC for MDM2 and then, analyzed the significance of prognosis. RESULTS: Forty-eight (6.8%) cases of a primary cardiac sarcoma were retrieved. The tumors most frequently involved the right atrium (n = 25, 52.1%), and the most frequent tumor subtype was angiosarcoma (n = 23, 47.9%). Seven cases (53.8%) were newly reclassified as an intimal sarcoma by IHC for MDM2. Twenty-nine (60.4%) patients died of disease (mean, 19.8 months). Four patients underwent a heart transplantation and had a median survival of 26.8 months. This transplantation group tended to show good clinical outcomes in the earlier stages, but this was not statistically significant (p = 0.318). MDM2 positive intimal sarcoma showed the better overall survival (p = 0.003) than undifferentiated pleomorphic sarcoma. Adjuvant treatment is beneficial for patient survival (p < 0.001), particularly in angiosarcoma (p < 0.001), but not in intimal sarcoma (p = 0.154). CONCLUSION: Our study supports the use of adjuvant treatment in primary cardiac sarcoma, as it was associated with a significantly better overall survival rate. Further consideration of tumor histology may be important in determining the optimal use of adjuvant treatment for different types of sarcomas. Therefore, accurate diagnosis by MDM2 test is important condsidering patient's prognosis and treatment.

Assessment of thyroid cartilage ossification pattern in cancer patients: A suggestion of active ossification by tumor progression.

BACKGROUND: Ossified cartilage is much more susceptible to cancer infiltration, but the reason remains unknown, and the relationship between the ossification pattern and cancer infiltration has not been studied. METHODS: The presence of thyroid cartilage ossification, cancer infiltration, ossification pattern (usual: direction from inferior to superior; unusual: other than the usual pattern), and distance between cancer and ossified cartilage were evaluated in laryngectomy specimens. RESULTS: There were 28 and 27 cases of usual and unusual patterns, respectively. There was no association between ossification pattern and cancer infiltration. However, the distance between the ossified area and cancer cells was greater in the usual pattern than in the unusual pattern (p = 0.006). And the usual pattern was more frequently observed in cases with a distance >1 mm than in cases with cancer infiltration or a distance ≤1 mm (p = 0.004). CONCLUSION: These results suggest the possibility of an active ossification due to tumor progression.

Frequent apocrine changes in pleomorphic adenoma with malignant transformation: a possible pre-malignant step in ductal carcinoma ex pleomorphic adenoma.

BACKGROUND: The most common type of carcinoma ex pleomorphic adenoma (CPA) is histologically equivalent to salivary duct carcinoma, which has an apocrine phenotype. Invasive CPA is often accompanied by non-invasive or in situ carcinoma, an observation that suggests the presence of precursor lesions. The aim of this study was to identify candidate precursor lesions of CPA within pleomorphic adenoma (PA). METHODS: Eleven resected cases of CPA with residual PA and 17 cases of PA with atypical changes were subjected to immunohistochemistry (IHC) for p53, human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), pleomorphic adenoma gene 1, gross cystic disease fluid protein-15 (GCDFP-15), and anti-mitochondrial antibody. RESULTS: Invasive or in situ carcinoma cells in all CPAs were positive for AR, GCDFP-15, and HER2. Atypical foci in PAs corresponded to either apocrine or oncocytic changes on the basis of their reactivity to AR, GCDFP-15, and anti-mitochondrial antibody. Atypical cells in PAs surrounding CPAs had an apocrine phenotype without HER2 expression. CONCLUSIONS: Our study identified frequent apocrine changes in residual PAs in CPA cases, suggesting a possible precursor role of apocrine changes. We recommend the use of HER2 IHC in atypical PAs, and that clinicians take HER2 positivity into serious consideration.

Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea.

BACKGROUND: Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study. METHODS: Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53. RESULTS: CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history. CONCLUSIONS: Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

Clinical and Radiological Features of Diffuse Lacrimal Gland Enlargement: Comparisons among Various Etiologies in 91 Biopsy-Confirmed Patients.

OBJECTIVE: To compare the clinical and radiological features of various etiologies of chronic diffuse lacrimal gland enlargement. MATERIALS AND METHODS: We retrospectively reviewed 91 consecutive patients who underwent surgical biopsy for chronic diffuse lacrimal gland enlargement and were diagnosed with non-specific dacryoadenitis (DA) (n = 42), immunoglobulin G4-related dacryoadenitis (IgG4-RD) (n = 33), and lymphoma (n = 16). Data on patient demographics, clinical presentation, and CT imaging findings (n = 73) and MRI (n = 43) were collected. The following radiologic features of lacrimal gland enlargement were evaluated: size, unilaterality, wedge sign, angle with the orbital wall, heterogeneity, signal intensity, degree of enhancement, patterns of dynamic contrast-enhanced, and apparent diffusion coefficient value. Radiological features outside the lacrimal glands, such as extra-lacrimal orbital involvement and extra-orbital head and neck involvement, were also evaluated. The clinical and radiological findings were compared among the three diseases. RESULTS: Compared to the DA and IgG4-RD groups, the lymphoma group was significantly older (mean 59.9 vs. 46.0 and 49.4 years, respectively; p = 0.001) and had a higher frequency of unilateral involvement (62.5% vs. 31.0% and 15.2%, respectively; p = 0.004). Compared to the IgG4-RD and lymphoma groups, the DA group had significantly smaller lacrimal glands (2.3 vs. 2.8 and 3.3 cm, respectively; p < 0.001) and a lower proportion of cases with a wedge sign (54.8% vs. 84.8% and 87.5%, respectively; p = 0.005). The IgG4-RD group showed more frequent involvement of the extra-orbital head and neck structures, including the infraorbital nerve (36.4%), paranasal sinus (72.7%), and salivary gland (58.6%) compared to the DA and lymphoma groups (4.8%-28.6%) (all p < 0.005). CONCLUSION: Patient age, unilaterality, lacrimal gland size, wedge sign, and extra-orbital head and neck involvement differed significantly different between lymphoma, DA, and IgG4-RD. Our results will be useful for the differential diagnosis and proper management of chronic lacrimal gland enlargement.

NY-ESO-1 as a diagnostic and prognostic marker for myxoid liposarcoma.

INTRODUCTION: Myxoid liposarcoma (MLS) is a common lipogenic sarcoma, which is difficult to diagnose in small specimens. New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) is a cancer-testis antigen expressed in neoplastic tissue. In this study, NY-ESO-1 expression was assessed in various soft tissue tumors (STTs), and we also evaluated its diagnostic utility. METHODS: We included 434 cases of STTs for collection of clinicopathological data. Tissue microarrays were designed, and immunostaining for NY-ESO-1 was examined. We investigated the correlation between NY-ESO-1 expression and various clinicopathological parameters. We also evaluated the role of NY-ESO-1 as a diagnostic marker for MLS and its possible use in prognostication. RESULTS: Sixty-four of the 434 STTs (14.75%) were immunoreactive for NY-ESO-1, and the most frequent type of tumor in the NY-ESO-1 positive group was MLS (70.3%, 45/64), followed by synovial sarcoma (17.2%, 11/64). MLS showed 72.6% (45/62) immunopositivity for NY-ESO-1. The sensitivity and specificity of NY-ESO-1 expression for the diagnosis of MLS were 84.4% and 100%, respectively, compared to DDIT3 fluorescence in situ hybridization. When restricting analysis to the MLS (n=62), the NY-ESO-1 positive group had a poor overall survival (OS) rate (P=0.039). CONCLUSION: NY-ESO-1 was substantially and widely expressed in the majority of MLS cases. NY-ESO-1 positivity by IHC staining was also a predictor of a poor OS in patients with MLS. It is possible to use NY-ESO-1 for diagnosis and for predicting a prognosis in patients with MLS, and it may be used as a therapeutic target.

Distinct histologic and genetic characteristics of round cell sarcoma with CIC-DUX4 fusion and comparison with ewing sarcoma.

CIC-DUX4 fusion gene associated sarcoma is a new emerging subgroup of round cell sarcoma with Ewing sarcoma-like morphology. Distinguishing these tumors from Ewing sarcoma family tumors (ESFT) is critical because of the clinical impact but is still challenging due to the overlapped histological and immunohistochemical phenotypes of each subtype. The present study investigated small round cell sarcoma to identify CIC-DUX4 fusion positive sarcoma, examined clinical, histopathologic and immunohistochemical characteristics of CIC-DUX4 sarcoma, and evaluated parameters to differentiate Ewing sarcoma family tumors. Seventy patients with undifferentiated round cell sarcoma or Ewing-like sarcoma were retrieved. Molecular tests including EWSR1, CIC break apart FISH, and RT-PCR for CIC-DUX4 gene fusion were performed and immunohistochemistry was performed. Six cases (8.6%) of CIC-DUX4 sarcomas were detected. Histologically, CIC-DUX4 sarcomas composed of heterogeneous round, plasmacytoid, and spindle cells and more commonly showed cytologic pleomorphism with bizarre nuclei and multinucleated cells and myxoid stoma unlike ESFT. CIC-DUX4 sarcomas didn't show overall survival differences (p = 0.325) compared to ESFT but they demonstrated short disease-free survival (p = 0.034) and poor response to treatment (p = 0.007). Therefore, molecular analysis to detect the distinctive genetic alteration is mandatory in tumors with atypical histologic, immunohistochemical and/or clinical presentation for accurate diagnosis and treatment.

A sinonasal yolk sac tumor in an adult.

Yolk sac tumors (YSTs), which are also called endodermal sinus tumors, are malignant tumors of germ cell origin. These tumors usually occur in the gonads, but 20% of cases have been reported at extragonadal sites. The head and neck is a rarely affected region that accounts for just 1% of all malignant tumors of germ cell origin. In addition, YSTs arise mostly in childhood. We present a rare pathologically pure case of primary adult YST in the sinonasal area. A 45-year-old male patient presented with a rapidly growing mass in the nasal cavity, which caused nasal obstruction and bloody post-nasal drip. The histopathologic features indicated pure YST, and immunohistochemical analysis revealed positive reactivity for Sal-like protein 4 and alpha-fetoprotein. Herein, we discuss the clinical, radiologic, and histologic features of this YST and review other cases of sinonasal YST in adults.

Clinicopathologic Characteristics and Clinical Outcome of Localized Liposarcoma: A Single-Center Experience over 25 Years and Evaluation of PD-L1 Expression.

PURPOSE: For liposarcoma (LPS), clinical course and proper treatment strategies have not been well-established. Recently, immune-checkpoint inhibitors have shown potential efficacy in LPS. We aimed to describe the clinical course of LPS and evaluate the clinical impact of programmed death-ligand 1 (PD-L1). MATERIALS AND METHODS: We reviewed all consecutive patients (n=332) who underwent curative-intent surgery for localized LPS at Asan Medical Center between 1989 and 2017. PD-L1 testing was performed in well-differentiated and dedifferentiated LPS. RESULTS: The median age was 56 years with males comprising 60.8%. Abdomen-pelvis (47.6%) and well-differentiated (37.7%) were the most frequent primary site and histologic subtype, respectively. During a median follow-up of 81.2 months, recurrence was observed in 135 (40.7%), and 86.7% (117/135) were loco-regional. Well-differentiated subtype (hazard ratio [HR], 0.38), abdomen-pelvis origin (HR, 2.43), tumor size larger than 5 cm (HR, 1.83), positive resection margin (HR, 2.58), and postoperative radiotherapy (HR, 0.36) were significantly related with recurrence-free survival as well as visceral involvement (HR, 1.84) and multifocality (HR, 3.79) in abdomen-pelvis LPS. PD-L1 was positive in 31.5% (23/73) and 51.3% (39/76) of well-differentiated and dedifferentiated LPS, respectively, but had no impact on survival outcomes. CONCLUSION: Clinical course of LPS was heterogeneous according to histology and anatomic location. Clear resection margin was important to lower recurrence and postoperative radiotherapy might have additional benefit. A decent portion of well-differentiated and dedifferentiated LPS were positive for PD-L1, but its prognostic role was unclear. Further research is needed to determine clinical implications of PD-L1, especially for advanced-stage LPS with unmet needs for effective systemic treatment.

Demographics, Changes in Treatment Patterns, and Outcomes of Bone and Soft Tissue Sarcomas in Korea-A Sarcoma-Specific, Institutional Registry-Based Analysis.

PURPOSE: Because of the heterogeneity of sarcomas, establishing a well-collected, sarcoma-specific database is important for sarcoma research. We analyzed the first histology-based, sarcoma-specific institutional registry in Korea, which collected 28 years of patient data according to a predefined data format. PATIENTS AND METHODS: Adult bone and soft tissue sarcoma patients who were treated from June 1989 to January 2017 were identified and analyzed, based on the ICD-O-3 codes. RESULTS: Among the 3420 patients included, soft tissue and bone sarcomas comprised 77.8% (n = 2661) and 22.2% (n = 759), respectively. Median age at diagnosis was 50 (range, 16-98) in soft tissue sarcomas and 37 (range, 16-85) in bone sarcomas. Males and females comprised 45.5% and 54.5% of soft tissue sarcomas and 52.7% and 47.3% of bone sarcomas, respectively. Among the 3407 patients with treatment data available, 90.5% of the patients with soft tissue sarcomas and 80.8% of the patients with bone sarcomas received surgery first, of which 57.8% and 71.7% did not receive any subsequent treatment, respectively. Overall, the proportion of patients who received surgery alone decreased from 85.7% to 60.5% from the pre-2000 period to the 2010-2017 period. However, the use of adjuvant chemotherapy increased in patients with soft tissue sarcomas (from 8.0% to 17.2% in the same period), and the use of perioperative radiotherapy also increased in both groups (from 1.4% to 22.7% in soft tissue sarcomas, and 0% to 14.5% in bone sarcomas in the same period). In both soft tissue and bone sarcomas, old age (≥65 years) and diagnosis in the early study period were associated with poorer survival. CONCLUSION: We presented a comprehensive summary of our sarcoma registry, including the demographics, changes in treatment patterns, and survival outcomes. This study will provide a framework for future studies.

Retinal granular cell tumor: a case report.

BACKGROUND: To report a rare case of granular cell tumor invading the retina. CASE PRESENTATION: A 56-year-old female complained of blurred vision for 2 weeks in her left eye. An irregular-shaped retinal mass in the inferonasal and extending to the optic disc accompanied by dense exudation and extensive serous retinal detachment was observed. Several intravitreal bevacizumab injections were ineffective for stabilizing retinal exudation and intraocular pressure (IOP). Vitrectomy was performed to re-attach the retina and obtain a tumor biopsy specimen. Histopathological analysis revealed that the intraocular mass was a granular cell tumor. Immunohistochemical studies demonstrated that the tumor was positive for S100 and CD68, focal positive for neurofilaments, but negative for ERG and HMB-45. Local recurrence and distant metastasis were not found, but visual acuity had worsened to no light perception at the last visit due to uncontrolled intraocular pressure and retinal exudation after the surgery. CONCLUSIONS: Granular cell tumor is a rare benign neoplasm, but it can lead to devastating visual loss if it invades the retina adjacent to the optic nerve head.

Clinico-cytopathologic analysis of 574 Pericardial Effusion Specimens: Application of the international system for reporting serous fluid cytopathology (ISRSFC) and long-term clinical follow-up.

INTRODUCTION: A pericardial effusion (PE) has a variable etiology and the primary role is diagnosis of metastatic malignancy. We analyzed the PE cytology in a large cohort in accordance with the international system for reporting serous fluid cytopathology (ISRSFC) and evaluated the long-term patient outcomes. METHODS: PE specimens from 2010 to 2014 with an available clinical history, cytologic data, and pericardial biopsy results were collected. RESULTS: A total of 574 PE specimens were obtained from 486 patients, representing 1.5% (574/38,589) of all body fluid specimens. Three hundred and eighty-two (66.6%) cases were "negative," 54 (9.4%) cases were "atypia of undetermined significance," 10 (1.7%) cases were "suspicious for malignancy," and 128 (22.3%) cases were "malignancy". The most common origin for malignant PE was the lung (82.1%), in both men (70.5%) and women (50.6%). Breast cancer (20%) in women and gastric cancer (4.9%) in men were the second most common malignant PE, respectively. The mean interval from the occurrence of malignant PE to death was 10.06 months (range; 0-116.03 months, median 3.5 months), and the 1-year survival rate was 16.7%. In addition, the 1-year survival rates after malignant PE onset were 0% for gastric cancer, 13.9% for lung cancer, 19.8% for breast cancer, and 21.1% for the other cancers (p = 0.011). CONCLUSION: Our present study is the first to our knowledge to classify the pericardial fluid from 574 cases in accordance with the recently published ISRSFC, and to present the long-term outcomes of patients with malignant PE at the same time. Moreover, we report for the first time that it is gastric and not lung cancer patients that have the poorest prognosis after the occurrence of malignant PE.

Genomic alteration in rare subtype of sarcomatoid salivary duct carcinoma.

AIMS: Salivary duct carcinoma (SDC) is an aggressive salivary gland neoplasm with a poor prognosis. Morphologically, it has many variants including sarcomatoid SDC. We evaluated the morphological features, immunohistochemistry profile, and genomic alteration of the rare variant, sarcomatoid SDC. METHODS AND RESULTS: We evaluated the clinicopathological and molecular pathology for rare variant of sarcomatoid SDC. Among 102 SDC patients, three had sarcomatoid SDC. Review of clinicopathological features and immunohistochemistry and targeted exome sequencing was performed according to carcinomatous and sarcomatoid areas, respectively. The tumors were present in two submandibular glands and one parotid gland. In one case, a SDC arose in carcinoma ex pleomorphic adenoma. All consisted of a conventional invasive ductal carcinoma area and sarcomatoid features including spindle cells and multinucleated giant cells. AR and epithelial membrane antigen (EMA) were positive in both carcinoma and sarcomatoid areas. Cytokeratin AE1/AE3 were negative in all sarcomatoid areas. Targeted exome sequencing revealed multiple heterogeneous alterations including PIK3CA and TP53. Genomic alterations were nearly identical between typical carcinoma and sarcomatoid areas. CONCLUSIONS: Clinicopathological features of sarcomatoid SDCs were not different from typical SDC, and genomic alteration according to subtypes was also similar to that of the conventional type. Androgen receptor (AR) expression is helpful in the diagnosis of SDC. The findings indicate that EMA and AR are useful in diagnosing sarcomatoid SDC when the tumor is composed of predominantly sarcomatoid components.

The Role and Clinical Effectiveness of Multiline Chemotherapy in Advanced Desmoplastic Small Round Cell Tumor.

BACKGROUND: A multimodal approach is the standard treatment for desmoplastic small round cell tumor (DSRCT); however, many patients are diagnosed with inoperable disease, which leaves chemotherapy as the only treatment option. There are limited data on the effectiveness of palliative chemotherapy, especially when used after first-line treatment. Here, we evaluated the clinical outcomes of patients with DSRCT treated with multiple lines of chemotherapy. METHODS: We reviewed medical records of 14 patients with pathologically confirmed DSRCT at Asan Medical Center between 2004 and 2018. RESULTS: The median age at diagnosis was 25, with males comprising 92.9% of patients. All patients had inoperable disease at presentation and received chemotherapy as the initial treatment. Four patients (28.6%) were treated with surgery, and complete resection was achieved in 1 patient. Median overall survival (OS) was 23.9 months, and 1-, 2-, and 3-year survival rates were 92.9%, 48.6%, and 19.5%, respectively. In patients receiving first- (N = 14), second- (N = 10), and third-line (N = 8) chemotherapy, median time-to-progression was 9.9, 3.5, and 2.5 months, respectively, and the disease control rates were 100%, 88.9%, and 75.0%, respectively. Factors associated with longer OS in the univariable analysis were ⩽2 metastatic sites at presentation (27.0 vs 14.7 months; P = .024) and surgery with intended complete resection (43.5 vs 20.1 months; P = .027). CONCLUSIONS: Although advanced DSRCT may initially respond to chemotherapy after first-line treatment, the response becomes less durable as the disease progresses. Individualized treatment decisions focused on palliation should be made.

Epigenetic regulation of p62/SQSTM1 overcomes the radioresistance of head and neck cancer cells via autophagy-dependent senescence induction.

Tumors are composed of subpopulations of cancer cells with functionally distinct features. Intratumoral heterogeneity limits the therapeutic effectiveness of cancer drugs. To address this issue, it is important to understand the regulatory mechanisms driving a subclonal variety within a therapy-resistant tumor. We identified tumor subclones of HN9 head and neck cancer cells showing distinct responses to radiation with different levels of p62 expression. Genetically identical grounds but epigenetic heterogeneity of the p62 promoter regions revealed that radioresistant HN9-R clones displayed low p62 expression via the creation of repressive chromatin architecture, in which cooperation between DNMT1 (DNA methyltransferases 1) and HDAC1 (histone deacetylases 1) resulted in DNA methylation and repressive H3K9me3 and H3K27me3 marks in the p62 promoter. Combined inhibition of DNMT1 and HDAC1 by genetic depletion or inhibitors enhanced the suppressive effects on proliferative capacity and in vivo tumorigenesis following irradiation. Importantly, ectopically p62-overexpressed HN9-R clones increased the induction of senescence along with p62-dependent autophagy activation. These results demonstrate the heterogeneous expression of p62 as the key component of clonal variation within a tumor against irradiation. Understanding the epigenetic diversity of p62 heterogeneity among subclones allows for improved identification of the functional state of subclones and provides a novel treatment option to resolve resistance to current therapies.