Indolent Clinical Behavior Research Articles

Updates in the treatment of mantle cell lymphoma: A Canadian expert framework

Mantle cell lymphoma (MCL) is a B cell Non-Hodgkin Lymphoma that develops in the mantle zone of the lymph node. It is more common in men and is usually diagnosed at an advanced stage with involvement of lymph nodes, bone marrow, and potentially the gastrointestinal tract. MCL accounts for 5–10% of all new NHL cases per year in Canada, which is estimated at 11,400 for 2022. While most patients respond to initial treatment, relapses occur early and MCL generally shows a variable response to subsequent treatments, often with limited duration of benefit. Two main subtypes of MCL can be distinguished that arise from in situ MCL lesions. The most common subtype, classic MCL, arises from these cells with limited or no immunoglobulin heavy chain variable region (IGHV) mutations. Cells from this subtype express SOX11, are genetically unstable, and have naïve B cell-like characteristics. Classic MCL is more often nodal and extranodal and may eventually progress to aggressive blastoid or pleomorphic MCL. The other subtype, leukemic non-nodal MCL, arises from cells that have undergone IGHV somatic hypermutations, do not express SOX11, and exhibit characteristics of memory B cells. This subtype can have an indolent clinical behavior for a long time, often several years, but frequently acquires TP53 and other mutations and progresses to a more aggressive subtype. Treatment options have expanded significantly over the past decades, with improvements in both overall survival (OS) and progression-free survival (PFS) compared to earlier treatment eras. This Canadian expert framework aims to discuss the management considerations for patients with MCL, and will present both front-line treatment options as well as those for relapsed and refractory disease.

Gastrointestinal Glomus Tumors: A Single Institution, 20-Year Retrospective Study

IntroductionGlomus tumors are rare mesenchymal neoplasms composed of cells resembling those of the thermoregulatory glomus body, typically occurring in the skin and superficial soft tissues. Rarely do they occur in the gastrointestinal tract, in particular the stomach, where they have been the subject of case reports and small series. We present our institutional experience with gastrointestinal glomus tumors. MethodsA retrospective review of all gastrointestinal glomus tumors was conducted across all three Mayo Clinic sites in Minnesota, Arizona, and Florida from 2001 to 2021. Patient characteristics, pathologic findings, imaging features, operative reports, and clinical outcomes were abstracted. Descriptive statistics were utilized to report outcomes. ResultsNine patients with glomus tumors were identified (five men and four women). The median age was 53 [interquartile range (IQR), 44-69] y. Four patients presented with abdominal discomfort, three had anemia or bleeding, and two tumors were incidentally diagnosed. Computed tomography scans identified masses thought to represent gastrointestinal stromal tumors or neuroendocrine tumors in all patients. The tumors were localized to the stomach in all cases, specifically in the gastric antrum. Seven patients underwent preoperative endoscopy, including five with endoscopic ultrasonography. Endoscopic biopsies were interpreted as glomus tumors (n = 3), neuroendocrine tumors (n = 2), and nondiagnostic (n = 2). All patients underwent open (n = 3) or minimally invasive (n = 6) margin-negative resection by wedge resection (n = 5) or distal gastrectomy (n = 4). No nodal metastases were identified radiographically or on pathologic examination. The median tumor size was 2.5 [IQR 1.3-3.4] cm. All tumors showed at least in part typical glomus tumor morphology and smooth muscle actin expression. Aberrant synaptophysin expression was present in the two tumors initially classified as NET. Using the current WHO criteria, tumors were classified as histologically malignant (n = 1) and of “uncertain malignant potential” (n = 8). At a median follow-up of 15 [IQR 1-56] mo, all patients were asymptomatic and without recurrence. Two patients died of unrelated causes. No patients received adjuvant therapies. ConclusionsOur 20-year, single institution, 3-site experience with resected gastrointestinal glomus tumors suggests the rarity, predisposition to involve the gastric antrum, and potentially an indolent clinical behavior of many of these tumors. Long-term follow-up is warranted as some previously reported gastric glomus tumors have metastasized, including cases lacking morphologic evidence of malignancy. Surgical resection, with minimally invasive wedge resection alone, is likely sufficient for the management of most gastric glomus tumors.

S-100 Negative Granular Cell Tumor of Oral Cavity with Aggressive Clinical Behavior

Abstract Introduction/Objective Granular cell tumors (GCTs) are neoplasms with neuroectodermal (Schwann cell) differentiation that is typically benign and cured by surgical excision. These tumors characteristically display strong expression of S-100 protein. Similar tumors without expression of S-100 protein are called “S-100 negative granular cell tumors.” The few reported cases of S-100 negative GCT in the oral cavity describe indolent clinical behavior. We report a case of a 49-year-old male with recurrent S-100 negative GCT in the oral cavity. Methods/Case Report The patient presented initially with a mass in the hard palate, which was resected and diagnosed as an S-100 negative GCT. One year later, the patient developed severe epistaxis and anemia (hemoglobin 7.2 g/dL). A large tumor of the hard palate was the source of bleeding. It was resected and diagnosed as recurrent S-100 negative GCT. Histologically, this tumor consists of small nests of epithelioid to spindled cells with moderately abundant granular eosinophilic cytoplasm, round central nuclei with vesicular chromatin and distinct eosinophilic nucleoli, and significant mitotic activity. The cells are immunoreactive for SOX10 and negative for S-100, melan-A, keratin AE1/AE3, p40, synaptophysin, smooth muscle actin, desmin, and myogenin. Results (if a Case Study enter NA) N/A Conclusion S-100 negative GCTs are rare, and only a few case reports describe their involvement in the oral cavity. We report this case because of its rarity and aggressive clinical behavior. Recognition of this entity and its potential for locally aggressive growth is important. Management of this tumor by complete excision seems advisable.

Gastrointestinal Glomus Tumors: Outcomes and Management Experiences

Introduction: Glomus tumors typically involve peripheric tissues, only rarely being reported in the gastrointestinal tract. We present our institutional experience with gastrointestinal glomus tumors. Methods: A retrospective review of all gastrointestinal glomus tumors was conducted across three Mayo Clinic Sites from 2001 to 2021. Descriptive statistics were used. Results: Five men and 4 women were identified, with a median age of 53 years (interquartile range [IQR] 44.3-69.15 years). Four patients presented abdominal discomfort, 3 anemia or bleeding, 2 were incidentally found. All CT scans showed masses thought to represent gastrointestinal stromal tumors or neuroendocrine tumors. Seven patients underwent preoperative endoscopy, including 5 ultrasonography. All tumors were localized at the stomach antrum. Endoscopic biopsies (7 patients) were interpreted as glomus tumor (n = 3), neuroendocrine tumor (n = 2) and non-diagnostic (n = 2). Patients underwent open (n = 3) or minimally invasive (n = 6) margin-negative resection by wedge resection (n = 5) or distal gastrectomy (n = 4). No nodal metastases were identified. Median tumor size was 2.5 cm (IQR 13-34 cm). Typical morphological and immunohistochemical features of glomus tumors were identified; tumors were classified as histologically benign (n = 7), histologically malignant (n = 1), and of uncertain malignant potential (n = 1). Next-generation sequencing on one tumor identified a CARMN::NOTCH2 fusion. Clinical follow-up (median 14.9 months; IQR 10-86 months) showed all patients to be symptom-free, without recurrences. Two patients died from unrelated causes. No patients received adjuvant therapy. Conclusion: Our 20-year experience with gastrointestinal glomus tumors confirms their rarity and generally indolent clinical behavior. As some gastrointestinal glomus tumors display malignant behavior despite benign histology, long-term follow-up is warranted.

Comparative proteomic and clinicopathological analysis of breast adenoid cystic carcinoma and basal-like triple-negative breast cancer.

BackgroundAdenoid cystic carcinoma (ACC) is a rare type of triple-negative breast cancer that has an indolent clinical behavior. Given the substantial overlapping morphological, immunohistochemical, and molecular features with other basal-like triple-negative breast cancer (BL-TNBC), accurate diagnosis of ACC is crucial for effective clinical treatment. The integrative analysis of the proteome and clinicopathological characteristics may help to distinguish these two neoplasms and provide a deep understanding on biological behaviors and potential target therapy of ACC.MethodsWe applied mass spectrometry-based quantitative proteomics to analyze the protein expression in paired tumor and adjacent normal breast tissue of five ACC and five BL-TNBC. Bioinformatic analyses and the clinicopathological characteristics, including histological features, immunohistochemistry, and FISH results, were also collected to get comprehensive information.ResultsA total of 307 differentially expressed proteins (DEPs) were identified between ACC and BL-TNBC. Clustering analysis of DEPs clearly separated ACC from BL-TNBC. GSEA found downregulation of the immune response of ACC compared with BL-TNBC, which is consistent with the negative PD-L1 expression of ACC. Vesicle-mediated transport was also inhibited, while ECM organization was enriched in ACC. The top upregulated proteins in DEPs were ITGB4, VCAN, and DPT. Moreover, in comparison with normal breast tissue, ACC showed elevated ribosome biogenesis and RNA splicing activity.ConclusionThis study provides evidence that ACC presents a substantially different proteomic profile compared with BL-TNBC and promotes our understanding on the molecular mechanisms and biological processes of ACC, which might be useful for differential diagnosis and anticancer strategy.

Aggressive variants of follicular cell-derived thyroid carcinoma: an overview.

The incidence of thyroid carcinoma has increased globally in the past years. Papillary thyroid carcinoma (PTC) is the most frequent neoplasm of the thyroid gland comprehending the 90% of the thyroid carcinoma and has an indolent clinical behaviour. However, some variants of follicular cell-derived thyroid carcinoma, including variants of classic of PTC, have been identified that show a more aggressive biological behaviour. An accurate diagnosis of these entities is crucial for planning a more aggressive treatment and improving patients' prognosis of patients. The aim of this review is to present the main clinical, histological, and molecular features of aggressive variants of follicular cell-derived thyroid carcinoma, and to provide useful histological parameters for determining the most suitable therapeutic strategy for patients affected by these forms. Variants of classic PTC such as the diffuse sclerosing variant (DSV), the tall cell variant (TCV), the columnar cell variant (CCV), the solid/trabecular variant (STV) and the hobnail variant (HV), and other variants of follicular cell-derived thyroid carcinoma, such as poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC), are associated with aggressive behaviour. The correct identification and diagnosis of aggressive variants of follicular cell-derived thyroid carcinoma is important, as they allow the clinician to adopt the most refined therapeutic strategies in order to the survival of the patients.

Mutations of 1p genes do not consistently abrogate tumor suppressor functions in 1p-intact neuroblastoma

BackgroundDeletion of 1p is associated with poor prognosis in neuroblastoma, however selected 1p-intact patients still experience poor outcomes. Since mutations of 1p genes may mimic the deleterious effects of chromosomal loss, we studied the incidence, spectrum and effects of mutational variants in 1p-intact neuroblastoma.MethodsWe characterized the 1p status of 325 neuroblastoma patients, and correlated the mutational status of 1p tumor suppressors and neuroblastoma candidate genes with survival outcomes among 100 1p-intact cases, then performed functional validation of selected novel variants of 1p36 genes identified from our patient cohort.ResultsAmong patients with adverse disease characteristics, those who additionally had 1p deletion had significantly worse overall survival. Among 100 tumor-normal pairs sequenced, somatic mutations of 1p tumor suppressors KIF1Bβ and CHD5 were most frequent (2%) after ALK and ATRX (8%), and BARD1 (3%). Mutations of neuroblastoma candidate genes were associated with other synchronous mutations and concurrent 11q deletion (P = 0.045). In total, 24 of 38 variants identified were novel and predicted to be deleterious or pathogenic. Functional validation identified novel KIF1Bβ I1355M variant as a gain-of-function mutation with increased expression and tumor suppressive activity, correlating with indolent clinical behavior; another novel variant CHD5 E43Q was a loss-of-function mutation with decreased expression and increased long-term cell viability, corresponding with aggressive disease characteristics.ConclusionsOur study showed that chromosome 1 gene mutations occurred frequently in 1p-intact neuroblastoma, but may not consistently abrogate the function of bonafide 1p tumor suppressors. These findings may augment the evolving model of compounding contributions of 1p gene aberrations toward tumor suppressor inactivation in neuroblastoma.

S171: MOLECULAR CLUSTERS OF IGM MONOCLONAL GAMMOPATHIES PRESENT DISTINCT BIOLOGIC, IMMUNE AND METABOLIC FEATURES

Background: IgM MGUS and Waldenstrom Macroglobulinemia (WM) represent a wide range of conditions whose management varies from observation to immunochemotherapy. The current classification relies solely on clinical features and does not explain the heterogeneity that exists within each of these conditions. Aims: To shed light on the biology that may account for the clinical differences, we performed the first comprehensive multi-omics analysis of IgM monoclonal gammopathies. Methods: We used bone marrow (BM) CD19+CD138+ sorted cells and matched BM plasma from 32 pts (7 IgM MGUS, 25 WM) and 5 healthy controls to perform whole exome sequencing, RNA-seq, proteomic and metabolomic analysis. 7 matched WM and 4 IgM MGUS pts were also evaluated using mass cytometry (CyTOF). Results: Applying principal component analysis to gene expression profiling, most of WM pts clustered together, while a small subset of them grouped separately with MGUS pts, suggesting a biologic dichotomy within WM. The controls formed a group distinct from most WM and MGUS pts. Fig1A We then applied a non-negative matrix factorization consensus clustering to the gene expression data and identified three robust clusters. Cluster 1 (C1) included only pts with WM, cluster 2 (C2) included pts with both WM and MGUS, and cluster 3 (C3) included all normal controls as well as a small number of WM and MGUS pts. Fig1B-C When mutations commonly identified in WM were analyzed, there was no difference among the three groups (excluding controls) in mutation burden of MYD88 L265P and CXCR4. Interestingly, aberrant expression of TNFAIP3 was a distinct feature of C1 as deletion of 6q (which encodes for TNFAIP3) and TNFAIP3 mutations were each significantly enriched in C1 (47%) compared to C2 (0%) and C3 (20%; p=0.04). Individual clusters associated with specific transcriptional signatures and clinical features. While C1 displayed enrichment of RNA processing, downregulation of inflammatory pathways and aggressive clinical behavior, C2 showed increased inflammatory signaling and senescence with indolent clinical behavior. C3 had intermediate features with combined proliferative and antigen response signatures. Fig1D In accordance with transcriptomics, the proteomic hallmark of C1 was upregulation of proteins involved in proliferation (eg AKT, MAPK) and downregulation of inflammatory proteins (eg IL4, IL10) while the opposite was observed in C2. Once more, C3 confirmed intermediate features with combined upregulation of proliferation and inflammatory proteins. The metabolism was rewired towards mitochondrial anabolism in C1 and C3, while towards glycolysis in C2. Accordingly, C1 and C3 showed undetectable concentrations of 3-hydroxybutyric acid as opposed to C2 which had increased levels of lactic acid, as end products of fatty acid oxidation and glycolysis respectively. Next, we explored whether C1 and C2 displayed a distinct immune profile. tSNE analysis showed that CD4+ T cells were more abundant in C2 compared to C1 while the opposite was observed for CD8+ T cells. Among CD4+ T cells, activated follicular helper (TFH; p=0.02) and regulatory (Treg; p=0.008) cells were predominantly expressed in C2. In contrast, C1 showed a higher expression of senescent T effector memory (TEM) cells. Fig1E In support of this, SPADE clustering analysis identified three clusters including TFH, Treg and TEM cells. Image:Summary/Conclusion: We have identified three molecular clusters in IgM monoclonal gammopathies with distinct clinical, proteomic, metabolomic and immune features, suggesting a potential biologic classification that may have therapeutic implications.

The EHA Research Roadmap: Malignant Lymphoid Diseases.

The EHA Research Roadmap: Malignant Lymphoid Diseases.

A Comprehensive Commentary on the Multilocular Cystic Renal Neoplasm of Low Malignant Potential: A Urologist's Perspective.

Simple SummaryMultilocular cystic renal neoplasm of low malignant potential (MCRNLMP) is a cystic renal neoplasm with an excellent prognosis. This neoplasm was previously named as “multilocular cystic renal cell carcinoma”, which is now considered obsolete. In 2016, the WHO distinguished this neoplasm of low malignant potential from cystic renal cell carcinomas, which have some overlapping morphologic features.Multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) is a cystic renal tumor with indolent clinical behavior. In most of cases, it is an incidental finding during the examination of other health issues. The true incidence rate is estimated to be between 1.5% and 4% of all RCCs. These lesions are classified according to the Bosniak classification as Bosniak category III. There is a wide spectrum of diagnostic tools that can be utilized in the identification of this tumor, such as computed tomography (CT), magnetic resonance (MRI) or contrast-enhanced ultrasonography (CEUS). Management choices of these lesions range from conservative approaches, such as clinical follow-up, to surgery. Minimally invasive techniques (i.e., robotic surgery and laparoscopy) are preferred, with an emphasis on nephron sparing surgery, if clinically feasible.

Clinical-Pathological and Molecular Evaluation of 451 NIFTP Patients from a Single Referral Center.

Simple SummaryNon-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) are follicular thyroid neoplasm with an indolent clinical behaviour. In this study, we evaluated a retrospective series of 451 NIFTPs, of which 197 (43.7%) presented in coexistence with collateral thyroid tumours. Unifocal and multifocal NIFTPs did not show peculiar ultrasound, cytological, molecular, and histo-pathological characteristics. Considering the high rate of coexisting carcinomas, NIFTP patients might benefit from monitoring of the contralateral lobe.Background: Non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) were introduced in thyroid pathology in 2016. NIFTPs are a group of follicular neoplasm with an indolent behaviour. In this study, we gathered a large retrospective cohort of NIFTPs and compared those presenting as solitary lesions and NIFTPs found in multifocal setting. Methods: A retrospective search of NIFTPs was performed, and the clinico-pathological features were recorded. For a subgroup of patients, pre-surgical ultrasound (US) evaluation, cytological diagnosis, and molecular analysis were available. Results: We collected 451 NIFTPs; 254 (56.3%) were truly solitary tumours, while 197 coexisted with one or more NIFTP/cancer. Contrasting unifocal and multifocal settings, NIFTPs size was the only significantly different parameter. Preoperatively, NIFTP nodules mostly showed low-risk US characteristics, indeterminate cytology and a RAS-like molecular profile. Conclusion: NIFTPs often coexist with collateral thyroid tumours. However, no clinical-pathological differences can be observed between solitary and “multifocal” NIFTPs. Despite the well-established clinical indolence of NIFTP, a careful monitoring of the contralateral lobe should not be excluded.

Recent Advances in the Genetic of MALT Lymphomas.

Simple SummaryMucosa-associated lymphoid tissue (MALT) lymphoma is the most common subtype of marginal zone lymphomas. These B-cell neoplasms may arise from many organs and usually have an indolent behavior. Recurrent chromosomal translocations and cytogenetic alterations are well characterized, some of them being associated to specific sites. Through next-generation sequencing technologies, the mutational landscape of MALT lymphomas has been explored and available data to date show that there are considerable variations in the incidence and spectrum of mutations among MALT lymphoma of different sites. Interestingly, most of these mutations affect several common pathways and some of them are potentially targetable. Gene expression profile and epigenetic studies have also added new information, potentially useful for diagnosis and treatment. This article provides a comprehensive review of the genetic landscape in MALT lymphomas.Mucosa-associated lymphoid tissue (MALT) lymphomas are a diverse group of lymphoid neoplasms with B-cell origin, occurring in adult patients and usually having an indolent clinical behavior. These lymphomas may arise in different anatomic locations, sharing many clinicopathological characteristics, but also having substantial variances in the aetiology and genetic alterations. Chromosomal translocations are recurrent in MALT lymphomas with different prevalence among different sites, being the 4 most common: t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). Several chromosomal numerical abnormalities have also been described, but probably represent secondary genetic events. The mutational landscape of MALT lymphomas is wide, and the most frequent mutations are: TNFAIP3, CREBBP, KMT2C, TET2, SPEN, KMT2D, LRP1B, PRDM1, EP300, TNFRSF14, NOTCH1/NOTCH2, and B2M, but many other genes may be involved. Similar to chromosomal translocations, certain mutations are enriched in specific lymphoma types. In the same line, variation in immunoglobulin gene usage is recognized among MALT lymphoma of different anatomic locations. In the last decade, several studies have analyzed the role of microRNA, transcriptomics and epigenetic alterations, further improving our knowledge about the pathogenic mechanisms in MALT lymphoma development. All these advances open the possibility of targeted directed treatment and push forward the concept of precision medicine in MALT lymphomas.

Characterization of Subtypes of BRAF-Mutant Papillary Thyroid Cancer Defined by Their Thyroid Differentiation Score.

The BRAFV600E mutation has been associated with more advanced clinical stage in papillary thyroid cancer (PTC) and decreased responsiveness to radioiodine (RAI). However, some BRAF mutant PTCs respond to RAI and have an indolent clinical behavior suggesting the presence of different subtypes of BRAF mutant tumors with distinct prognosis. To characterize the molecular and clinical features of 2 subtypes of BRAF-mutant PTCs defined by their degree of expression of iodine metabolism genes. 227 BRAF-mutant PTCs from the Cancer Genome Atlas Thyroid Cancer study were divided into 2 subgroups based on their thyroid differentiation score (TDS): BRAF-TDShi and BRAF-TDSlo. Demographic, clinico-pathological, and molecular characteristics of the 2 subgroups were compared. Compared to BRAF-TDShi tumors (17%), BRAF-TDSlo tumors (83%) were more frequent in blacks and Hispanics (6% vs 0%, P = 0.035 and 12% vs 0%, P = 0.05, respectively), they were larger (2.95 ± 1.7 vs 2.03 ± 1.5, P = 0.002), with more tumor-involved lymph nodes (3.9 ± 5.8 vs 2.0 ± 4.2, P = 0.042), and a higher frequency of distant metastases (3% vs 0%, P = 0.043). Gene set enrichment analysis showed positive enrichment for RAS signatures in the BRAF-TDShi cohort, with corresponding reciprocal changes in the BRAF-TDSlo group. Several microRNAs (miRs) targeting nodes in the transforming growth factor β (TGFβ)-SMAD pathway, miR-204, miR-205, and miR-144, were overexpressed in the BRAF-TDShi group. In the subset with follow-up data, BRAF-TDShi tumors had higher complete responses to therapy (94% vs 57%, P < 0.01) than BRAF-TDSlo tumors. Enrichment for RAS signatures, key genes involved in cell polarity and specific miRs targeting the TGFβ-SMAD pathway define 2 subtypes of BRAF-mutant PTCs with distinct clinical characteristics and prognosis.

Cytogenetic Alterations Are Differently Associated with Disease Progression Depending on t(14;18) in Follicular Lymphoma

[Introduction] Follicular Lymphoma (FL) is characterized by indolent clinical behavior and subsequent histological transformation which links to aggressive clinical course and poor outcome. The hallmark of cytogenetic abnormality in FL is the translocation t(14;18)(q32;q21), which is found in more than 75% of cases. Several other cytogenetic abnormalities, which might contribute to disease progression, have been found. However, the prognostic and biological significance of cytogenetic or genomic features of FL has not been fully revealed. Last year we have shown clear evidence that cytogenetic abnormalities, +21 and 3q27, were independent prognostic factor in the rituximab era. Next we evaluated the pattern of chromosomal abnormalities in FL and the relation between cytogenetic and biological feature in this study.[Patients and Methods] Cells from lymph nodes or other sites of disease at diagnosis from 201 patients with FL admitted to our hospital and affiliated hospitals between 2001 and 2013 were cytogenetically analyzed using standard methods of G-banding. Ninety nine (49.3%) men and 102 (50.7%) women with a median age of 59 years (range, 28 - 83 years) were included in the analysis. The median follow up period was 48.3 months. Forty three patients (21.4%) were Stage I or II; 156 patients (77.6%) were Stage III or IV; and 2 patients (1%) were unknown. Eighty patients (39.8%) were follicular lymphoma international prognostic index (FLIPI) low, 55 patients (27.4%) were intermediate, and 43 patients (21.4%) were high; and 23 patients (11.4%) were unknown. The distribution of FL pathological subgroups was as follows: FL Grade 1 - 2, 142 patients (70.6%); FL Grade 3a, 30 (15.0%); and unknown, 29 (14.4%). One hundred and fifty seven patients (78.1%) received Rituximab-containing chemotherapy as an initial treatment.[Result] t(14;18)(q32;q21) was the most common abnormality observed in 119 patients (59.2%). Other numerical or structural abnormalities that were identified in more than 5% of the patients were as follows: +X (17.9%), del(6)(q) / −6 (16.9%), +7 (14.4%), abnormality of 1q12-21 / 1q (12.9%), del(13)(q) / -13 (11.9%), abnormality of 3q27 (10.4%), abnormality of 10q22-24 (10.0%), +12 / dup(12)(q) (10.0%), abnormality of 1p21-22 / 1p(9.0%), +18 (9.0%), del(17)(p) / −17 (5.0%), and the number of cytogenetic aberration higher than 3 (54.7%). Patients with the number of cytogenetics aberration higher than 3 significantly correlated with higher FLIPI grade (p= 0.0028). As is the case with much higher number of aberration (higher than 4, p= 0.0019 and higher than 5, p= 0.0024). The higher number of cytogenetic aberration also showed a trend of good correlation with advanced stage of Ann Arbor system. These suggest that additional chromosomal aberration closely related to disease progression in FL. To investigate the relationship between the disease progression and each cytogenetic abnormality logistic regression analysis was performed. In all cohort +X (Oods Ratio (OR) 2.604, 95%CI 1.184 - 5.751, p= 0.0175) and +12 / dup(12)(q) (OR 3.955, 95%CI 1.397 - 12.22, p= 0.0095) were significant abnormalities for higher FLIPI grade. To evaluate significance of t(14;18) multivariate analysis was performed for both FLs with and without t(14;18) again. In FLs with t(14;18) the same cytogenetic abnormalities, +X (OR 3.293, 95%CI 1.212 - 9.459, p= 0.0216,) and +12 / dup(12)(q) (OR 6.748, 95%CI 1.779 - 33.998, p= 0.0042), were detected as significant factor for disease progression. On the contrary in FLs without t(14;18) quite different cytogenetic abnormalities, such as +5 (OR 4.01e7, 95%CI 2.180 - , p= 0.0144) and +21 (OR 11.065, 95%CI 1.318 - 232.1, p= 0.0267), were chosen. However, these cytogenetic abnormalities did not influence patients' survival except for +21.[Conclusion] In patients with FL disease progression was closely associated with cytogenetic abnormalities, +X and +12 / dup(12)(q) in those with t(14;18). However, in patients without t(14;18) disease progression developed in distinct manner with respect of cytogenetic alteration. Important cytogenetic alterations for disease progression may be different from those for survival in Rituximab era. DisclosuresMurakami:Ono: Honoraria; BMS: Honoraria; Fujimoto: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Celgene: Honoraria.

Clinical characteristics and long-term outcomes of 97 Korean patients with mycosis fungoides.

Mycosis fungoides (MF) shows racial and regional differences in terms of clinical features. The availability of therapeutic options as well as drugs differs from one country to another. There are only limited data on the clinical characteristics and treatment experience of MF from South Korea. Medical records of 97 patients with MF were retrospectively analyzed to investigate clinical features, survivals, and prognostic factors. Assessment of prognostic variables was done using univariate Cox proportional hazard models. Median age at time of diagnosis was 45 years. The median time from onset of skin lesion to diagnosis of MF was 36 months with a median follow-up period of 96 months. A number of clinical variants of MF were observed. Treatment mainly consisted of narrow-band UVB, systemic retinoids, methotrexate, chemotherapy, and regional radiotherapy. Complete remission was observed in 78% of patients with records on their clinical course. About 12% experienced disease progression. No clinical prognostic factor apart from TNM staging was identified. Despite delay in diagnosis, most cases of MF in Korea were diagnosed in early stages. Prognosis of our patients was more favorable than those of other geographic regions as reported in previous studies. Good response to treatment, consisting mainly of phototherapy and radiation therapy, and relatively indolent clinical behavior of disease were observed in this homogeneous cohort of Korean patients with MF.

Classic Kaposi sarcoma in a patient of Miao ethnicity followed up for 7 years: a case report

BackgroundClassic Kaposi sarcoma (CKS) is a vascular sarcoma associated with human herpesvirus 8 (HHV-8), which is known to be more common in Mediterranean elderly men and is characterized by indolent clinical behavior. Xinjiang province in China is considered an endemic region for Kaposi’s sarcoma-associated herpesvirus (KSHV), with higher incidence among adults of Kazak and Uyghur ethnicities. Cases of CKS are rarely reported in inland China. Here, we followed a case of CKS for 7 years in a patient of Miao ethnic background in southwestern China.Case presentationA 63-year-old Miao (southwestern China) man was initially diagnosed with CKS in 2010, having a history of limb lesions for 37 years, with left eyelid and binaural lesions for 9 years. He did not have sexual contact with men and was human immunodeficiency virus (HIV)-negative. Due to his lumbago and fever, spinal tuberculosis in the lumbar vertebra was highly suspected after computed tomography (CT) scan. However, diagnostic antituberculosis treatment for 4 weeks failed. The patient was followed up in 2016, when the rash was recovering as the systemic symptoms improved. A new CT was performed, which showed a partial response despite the absence of any medical treatment. The open reading frame (ORF)-K1 of KSHV from skin tissue of the foot was amplified and sequenced, and K1 belonged to subtype A. This genotype is consistent with the typical subtype present in Xinjiang.ConclusionsWe describe spontaneous partial regression of CKS in a patient of Miao ethnicity in inland China. Our sample may represent an unknown, novel genotype. Surveillance and regulating the immune state may represent a valuable approach for this rare disease.

26. Chromosomal characterization of six new cases of Mucinous tubular and spindle cell carcinoma of the kidney

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma (RCC), recognized as a distinct entity in the 2004 World Health Organization (WHO) tumor classification. It has indolent clinical behavior and characteristic histological features with an admixture of low-grade elongated tubules and bland spindle cells in a mucinous or myxoid stroma. Genetic studies of MTSCC are limited with only 5 reported cases of karyotype analysis, less than 80 cases for chromosome copy number analysis and 15 with next generation sequencing studies.

Update on Endometrial Stromal Tumours of the Uterus.

Endometrial stromal tumours (ESTs) are rare, intriguing uterine mesenchymal neoplasms with variegated histopathological, immunohistochemical and molecular characteristics. Morphologically, ESTs resemble endometrial stromal cells in the proliferative phase of the menstrual cycle. In 1966 Norris and Taylor classified ESTs into benign and malignant categories according to the mitotic count. In the most recent classification by the WHO (2020), ESTs have been divided into four categories: Endometrial Stromal Nodules (ESNs), Low-Grade Endometrial Stromal Sarcomas (LG-ESSs), High-Grade Endometrial Stromal Sarcomas (HG-ESSs) and Undifferentiated Uterine Sarcomas (UUSs). ESNs are clinically benign. LG-ESSs are tumours of low malignant potential, often with indolent clinical behaviour, with some cases presented with a late recurrence after hysterectomy. HG-ESSs are tumours of high malignant potential with more aggressive clinical outcome. UUSs show high-grade morphological features with very aggressive clinical behavior. With the advent of molecular techniques, the morphological classification of ESTs can be integrated with molecular findings in enhanced classification of these tumours. In the future, the morphological and immunohistochemical features correlated with molecular categorisation of ESTs, will become a robust means to plan therapeutic decisions, especially in recurrences and metastatic disease. In this review, we summarise the morphological, immunohistochemical and molecular features of ESTs with particular reference to the most recent molecular findings.

P50.03 Lung Neuroendocrine Tumors. 12-Years Experience of a Single Cancer Institution

Lung neuroendocrine tumors (NETs) are an uncommon group of pulmonary neoplasms that are characterized by neuroendocrine differentiation and relatively indolent clinical behavior. Lung is the second most common frequently involved site. There are no data in Mexican or Latin American populations regarding the clinical and pathologic characteristics as well as the prognosis in patients with NETs.

IPSILATERAL SYNCHRONOUS MUCINOUS TUBULAR AND SPINDLE CELL CARCINOMA AND CLEAR CELL PAPILLARY RENAL CELL CARCINOMA: A CASE REPORT AND REVIEW OF THE LITERATURE

Renal cell carcinoma (RCC), the most common solid lesion of the kidney, accounts for approximately 2%-3% of all malignancies among adults. Clear cell carcinoma and papillary cell carcinoma are the most common types of renal tumors. Some case reports have described synchronous benign and malignant tumors in the same kidney. In particular, angiomyolipoma and RCC in patients with tuberous sclerosis (TSC) and non-TSC have been reported many times in the literature. However, unilateral concordance of malignant renal tumors is very rare; thus, only few cases have been reported in the literature.Here we report the case of a 58-year-old male who had ipsilateral synchronous mucinous tubular and spindle cell carcinoma (MTSCC) and clear cell papillary renal cell carcinoma (CCPRCC). Both cancers are rare and relatively recently defined subtypes of RCC. Additionally, both were successfully treated using partial nephrectomy. MTSCC has been a distinct entity in the World Health Organization classification of kidney tumors since 2004. The classic type of MTSCC is characterized by small elongated tubules lined with clear cuboidal or spindle cells with mucinous stroma. Neoplastic cells always exhibit low-grade histological features. However, unclassified variants of MTSCC, such as mucin-poor, papillary, high-grade, and sarcomatoid variants, have also been reported. MTSCC is considered to have a relatively good prognosis, but some patients with poor prognoses have recently been reported. CCPRCC is a recently recognized entity and represents the fourth most common variant of RCC. It has unique morphological and immunohistochemical features and shows indolent clinical behavior. Microscopically, CCPRCC may mimic other RCCs with clear cell features, such as clear cell RCC, translocation RCC, and papillary RCC, with clear cell changes. In 2006, CCPRCC was described as a subtype of renal tumors in patients with end-stage renal disease. However, currently, CCPRCC has also been shown to occur in kidneys with normal function.To the best of our knowledge, this is the first report of ipsilateral synchronous MTSCC and CCPRCC, which we present with a review of the pertinent literature.