Immunohistochemical Prognostic Factors Research Articles

Abstract 3831: Clinicopathologic determinants of survival in double/triple hit lymphoma: Analysis of a pooled database

Abstract Background B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements are classified as double/triple- hit lymphoma (DTHL). They usually, but not always, tend to be high-grade aggressive B-cell lymphoma with worse prognosis. Despite this classification, DTHL remains a heterogeneous group with varied molecular profiles, biological behavior, and prognosis. Therefore, we conducted this pooled database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies influencing survival in this rare disease. Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 161 cases that fit the diagnostic criteria for DTHL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS). Results A compiled a dataset of 161 patients with confirmed DTHL. The median age was 62 with F:M of 1.08. The median duration of symptoms before diagnosis was 2 months. DTHL involved the lymph nodes (41%), bone marrow (31%), bone (14%), CNS (5%), skin (4%), liver (3%), and spleen (2%). Constitutional symptoms were reported in 20%. The cohort consisted of primary (50%), secondary/transformed (16%), and follicular DTHL. The median OS and DFS of the cohort were 69 and 27 months, respectively. Bone marrow and extra-lymphatic organ involvement were associated with worse DFS and non-significant numerically worse OS. LDH>500 (p=0.006), PAX5-negative (p=0.01), CD79a-negative (p=0.02), and Ki67>80% (p<0.0001) were associated with worse OS. Similarly, CD5+, CD10+, and MUM1+ had worse OS, but did not reach statistical significance. Follicular DTHL was associated with the best median OS and DFS followed by primary then secondary/transformed in decreasing order. Advanced stage and high IPI were also associated with worse non-significant numerical OS. Age and sex did not impact OS. Compared to no treatment, chemotherapy and stem cell transplant had incrementally superior median OS (3 vs. 55 vs. NR months, p=0.008). Frontline intensive chemotherapy yielded similar DFS and OS to CHOP-like regimens. Patients who attained CR as their best response also had a superior median OS (p<0.0001). Conclusion This study presents clinicopathologic data from a cohort of patients with primary, secondary, and follicular DTHL. It identifies the type of DTHL, IHC profile, LDH levels, type of therapy, and quality of response to treatment as critical determinants of OS. Citation Format: Philip A. Haddad, Supriya Gupta, Ankita Gupta, Christopher Graham. Clinicopathologic determinants of survival in double/triple hit lymphoma: Analysis of a pooled database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3831.

Abstract 3832: Fluid-overload associated large B-cell lymphoma and determinants of outcomes: Analysis of a pooled database

Abstract Background: Fluid overload-associated large B-cell lymphoma (FOLBCL) is a new WHO lymphoma entity previously known as PEL-like lymphoma or HHV8-unrelated PEL-like lymphoma. It is a rare lymphoma that arises within fluid-filled body cavities without a solid component. FOLBCL occurs in the absence of immunodeficiency and is commonly associated with conditions associated with fluid overload. It expresses mature B-cell phenotype and occasional EBV infection markers. We conducted this study to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect outcomes in this rare and newly defined lymphoma subtype. Materials & Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 115 cases that fit the diagnostic criteria for FOLBCL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 115 patients with confirmed FOLBCL were identified. The median age was 74, with a peak incidence between 72 and 82 years. There was a male preponderance with M:F of 2. The pleural, pericardial, and peritoneal cavities were involved in 75%, 34, and 27%. The median duration of symptoms before diagnosis was 1 month. Patients presented with constitutional symptoms and hepatosplenomegaly in 13% and 1%, respectively—no patients presented with lymph node and bone marrow involvement. The median OS of the whole group was 16 months. Patients younger than 70 had better median OS than 70 and older (24 vs. 10 months, p=0.008). The presence of any malignant peritoneal effusion was associated with worse OS when compared to effusion limited to the thoracic cavity (7 vs. 24 months, p=0.005). LDH>500 was also associated with worse OS (p=0.02). Sex, the presence of fluid overload-causing conditions, and serum IL2R levels did not seem to impact OS. MYC re-arrangement had numerically worse OS when present but did not reach statistical significance. Chemotherapy demonstrated superior OS compared to no treatment (24 vs. 7 months, p=0.009). Patients who attained CR as their best response had a superior median OS (p<0.0001). Conclusion: This study presents updated clinicopathologic data from a pooled cohort of patients with FOLBCL. It identifies the age, the primary location of cavitary disease, LDH, active therapy, and quality of response to treatment as key determinants of OS. Citation Format: Philip A. Haddad, Supriya Gupta, Christopher Graham. Fluid-overload associated large B-cell lymphoma and determinants of outcomes: Analysis of a pooled database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3832.

Abstract 3835: Clinicopathologic determinants of survival in malignant histiocytic neoplasms: Analysis of a pooled database

Abstract Background: Malignant histiocytosis, also known as the M-group per the Histiocyte Society classification, represents a rare, aggressive malignant group of histiocytic neoplasms. It includes histiocytic neoplasms that occur de novo (pMHN) and those that develop in association with other malignant diseases (aMHN). However, little is known about factors that impact MHN clinical outcomes. We conducted this pooled database analysis to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect survival in these rare diseases. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 281 cases of MHN. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 281 patients with confirmed MHN were identified, with 77% pMHN and 23% aMHN. The median age was 45, with bimodal peaks between 0-13 and 52-65. There was a male preponderance with M:F of 1.6. Primary sites of involvement were liver (15%), CNS and spleen (13% each), thoracic, GI, and soft tissues (12% each), bones (11%), skin (10%), H&N (8%), and breast, heart, gonads, pancreas, and kidney (1% each). Lymphadenopathy and bone marrow (BM) were involved in 28% and 18%, respectively. Constitutional symptoms occurred in 12% and hemophagocytic syndrome (HPS) in 6%. The median OS of the whole group was 12 months. BM involvement had a worse median OS (5 vs. 60 months, p=0.0002). Stage 1 disease had better median OS than higher stages (p=0.0008). Furthermore, unifocal had better median OS than multifocal/multicentric disease (60 vs. 7 months, p=0.0001). The presence of inflammatory background positively impacted OS (p=0.01). The occurrence of HPS adversely affected OS (p<0.0001). Compared to no treatment, localized therapies such as surgery (S) and/or radiation therapy (RT) and systemic combination chemotherapy (CT) were statistically superior, with a median OS of 3, 24, and 16 months, respectively (p=0.009). Among systemic therapies, SCT and BRAF/MEK inhibitors were superior to conventional chemotherapy (p=0.02). Having CNS or splenic-lymphatic primary involvement tended to have a numerical but non-significant worse median OS than soft tissue or visceral disease. While female sex, size<10cm, and pMHN seemed to have numerically better OS, they did not reach statistical significance. There was no difference in median OS for age. Conclusion: This study presents updated clinicopathologic data from a pooled cohort of patients with MHN. It identifies BM involvement, stage, extent of the disease, the inflammatory background status, occurrence of HPS, and treatment approach as critical determinants of OS. Citation Format: Philip A. Haddad, Dinesh Keerty. Clinicopathologic determinants of survival in malignant histiocytic neoplasms: Analysis of a pooled database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3835.

Abstract 3833: Primary cutaneous diffuse large B-cell lymphoma-leg type and clinicopathologic determinants of survival: Analysis of a pooled database

Abstract Background: Primary Cutaneous Diffuse Large B-cell Lymphoma-Leg Type (PCDLBCL-LT) is a rare but non-indolent subtype of B-cell lymphoma. While most PCDLBCL-LT starts over the lower extremities, some cases may present at other cutaneous sites. The determinants of survival outcomes in this disease are not very well defined. Therefore, we conducted this pooled database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies that influence survival in this disease. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 122 cases that fit the diagnostic criteria for PCDLBCL-LT. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS). Results: A total of 122 patients with confirmed PCDLBCL-LT were identified. The median age was 76. There was a male preponderance with M:F of 2.4. Seventy-three percent involved the extremities. The median duration of symptoms before diagnosis was 3.5 months. Involvement of lymph nodes, bone marrow, bone, and CNS occurred in 11%, 3%, 4%, and 3%, respectively. Constitutional symptoms were reported in 5%. The median OS and DFS of the whole group were 39 and 32 months, respectively. Patients younger than 70 had better median DFS (NR vs. 24 months, p=0.02) with a non-significant better median OS. Lymphadenopathy (45 vs. 18 months, p=0.006) and stage T3 compared to T1/T2 (16 vs 41 months, p=0.006) were associated with worse OS. Sex, constitutional symptoms, IHC phenotype, extra-lymphatic/extra-cutaneous organ involvement, and histologic cutaneous patterns did not impact OS. Compared to no treatment, chemotherapy, XRT+/-surgery, and stem cell transplant had numerically better OS without reaching statistical significance (5 vs. 39 vs. 41 vs. NR months, p=0.15). Patients who attained CR as their best response also had a superior median OS compared to responses less than CR and none (61 vs. 23 vs. 11 months, p<0.0001). Conclusion: This study presents updated clinicopathologic data from a large, pooled cohort of patients with PCDLBCL-LT. It identifies age, lymph node involvement, T stage, type of therapy, and quality of response to treatment as critical determinants of OS. Citation Format: Philip A. Haddad, Millicent Amankwah. Primary cutaneous diffuse large B-cell lymphoma-leg type and clinicopathologic determinants of survival: Analysis of a pooled database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3833.

Malignant Histiocytic Neoplasms' Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Background: Malignant histiocytosis, also known as the M-group per the Histiocyte Society classification, represents a rare, aggressive malignant group of histiocytic neoplasms. It includes histiocytic neoplasms that occur de novo (pMHN) and those that develop in association with other malignant diseases (aMHN). However, little is known about factors that impact MHN clinical outcomes. We conducted this pooled database analysis to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect survival in this rare histiocytic group. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 270 cases of MHN. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 270 patients with confirmed MHN were identified, with 77% pMHN and 23% aMHN. The median age was 45, with bimodal peaks between 13-26 and 52-65. There was a male preponderance with M:F of 1.6. The most common primary sites of involvement were liver (15%), CNS and spleen (13% each), thoracic, GI, and soft tissues (12% each), bones (11%), skin (10%), and H&N (8%). Lymphadenopathy and bone marrow (BM) were involved in 28% and 18%, respectively. Constitutional symptoms occurred in 12% and hemophagocytic syndrome (HPS) in 6%. The median time of MHN onset in aMHN was 12 months. The median OS of the whole group was 12 months. BM involvement had a worse median OS (p = 0.003). Stage 1 disease had better median OS than higher stages (p = 0.01). Furthermore, unifocal had better median OS than multifocal/multicentric disease (p = 0.0005). The presence of inflammatory background positively impacted OS (p = 0.01). The occurrence of HPS adversely affected OS (p < 0.0001). Compared to no treatment, localized therapies such as surgery (S) and/or radiation therapy (RT) and systemic combination chemotherapy (CT) were statistically superior, with a median OS of 3, 24, and 18 months, respectively (p = 0.02). When MHN was not amenable to complete resection, CT and CT+/-S+/-RT were superior to RT+S (p = 0.03). Having CNS or splenic-lymphatic primary involvement tended to have a numerical but non-significant worse median OS than soft tissue or visceral disease. While female sex, size<10cm, and pMHN seemed to have numerically better OS, they did not reach statistical significance. There was no difference in median OS for age. Conclusions: This study presents updated clinicopathologic data from a pooled cohort of patients with MHN. It identifies BM involvement, stage, extent of the disease, the inflammatory background status, occurrence of HPS, and treatment approach as critical determinants of OS.

Fluid-Overload Associated Large B-Cell Lymphoma Clinicopathologic Features and Determinants of Outcomes: Analysis of a Pooled Database

Background: Fluid overload-associated large B-cell lymphoma (FOLBCL) is a new WHO lymphoma entity previously known as PEL-like lymphoma or HHV8-unrelated PEL-like lymphoma. It is a rare lymphoma that arises within fluid-filled body cavities without a solid component. FOLBCL occurs in the absence of immunodeficiency and is commonly associated with conditions associated with fluid overload. It expresses mature B-cell phenotype and occasional EBV infection markers. We conducted this study to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect outcomes in this rare and newly-defined lymphoma subtype. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 115 cases that fit the diagnostic criteria for FOLBCL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 115 patients with confirmed FOLBCL were identified. The median age was 74, with a peak incidence between 72 and 82 years. There was a male preponderance with M:F of 2. The pleural, pericardial, and peritoneal cavities were involved in 75%, 34%, and 27%, respectively. The median duration of symptoms before diagnosis was 1 month. Patients presented with constitutional symptoms and hepatosplenomegaly in 13% and 1%, respectively-no patients presented with lymph node and bone marrow involvement. The median OS of the whole group was 16 months. Patients younger than 70 had better median OS than 70 and older (24 vs. 10 months, p=0.008). The presence of any malignant peritoneal effusion was associated with worse OS when compared to effusion limited to the thoracic cavity (7 vs. 24 months, p=0.005). LDH≥500 was also associated with worse OS (p=0.02). Sex, the presence of fluid overload-causing conditions, and serum IL2R levels did not seem to impact OS. Compared to no treatment, chemotherapy had a numerically superior OS but did not reach statistical significance (19 vs. 10 months, p=0.11). However, patients that attained CR as their best response had a superior median OS (p<0.0001). Conclusions: This study presents updated clinicopathologic data from a pooled cohort of patients with FOLBCL. It identifies the age, the primary location of cavitary disease, LDH, active therapy, and quality of response to treatment as key determinants of OS.

Double/Triple Hit Lymphoma Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Background B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements is classified as double/triple-hit lymphoma (DTHL). They usually, but not always, tend to be high-grade aggressive B-cell lymphoma with a worse prognosis. Despite this classification, DTHL remains a heterogeneous group with varied molecular profiles, biological behaviors, and prognoses. Therefore, we conducted this pooled database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies influencing survival in this rare disease. Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 161 cases that fit the diagnostic criteria for DTHL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS). Results We compiled a dataset of 161 patients with confirmed DTHL. The median age was 62, with an F:M of 1.08. The median duration of symptoms before diagnosis was 2 months. DTHL involved the lymph nodes (41%), bone marrow (31%), bone (14%), CNS (5%), skin (4%), liver (3%), and spleen (2%). Constitutional symptoms were reported in 20% of cases. The cohort consisted of primary (50%), secondary/transformed (16%), and follicular DTHL (34%). The median OS and DFS of the cohort were 69 and 27 months, respectively. Bone marrow and extra-lymphatic organ involvement were associated with worse DFS and non-significant numerically worse OS. LDH>500 (p=0.006), PAX5-negative (p=0.01), CD79a-negative (p=0.02), and Ki67>80% (p<0.0001) were associated with worse OS. Similarly, CD5+, CD10+, and MUM1+ had worse OS but did not reach statistical significance. Follicular DTHL was associated with the best median OS and DFS, followed by primary, then secondary/transformed in decreasing order. Advanced stage and high IPI were also associated with worse non-significant numerical OS. Age and sex did not impact OS. Compared to no treatment, chemotherapy and stem cell transplant had incrementally superior median OS (3 vs. 55 vs. NR months, p=0.008). Frontline intensive chemotherapy yielded similar DFS and OS to CHOP-like regimens. Patients who attained CR as their best response also had a superior median OS (p<0.0001). Conclusion This study presents clinicopathologic data from a cohort of patients with primary, secondary, and follicular DTHL. It identifies the type of DTHL, IHC profile, LDH levels, type of therapy, and quality of response to treatment as critical determinants of OS. Depending on the type (de novo, secondary, or follicular), DTHL seems to behave like 3 different disease entities.

Plasmablastic Lymphoma Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Background Plasmablastic Lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin's lymphoma. It tends to be associated with immunosuppressive clinical contexts, such as HIV infection and immunosuppressive therapies for autoimmune disorders and organ transplants. However, due to the rarity of the disease, which is poorly understood, varied treatment approaches have been implemented, and no optimal data or guidelines for managing PBL are available. Furthermore, a few small case series reported conflicting prognosticators. Therefore, we conducted this pooled database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies influencing survival in this rare disease. Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 300 cases that fit the diagnostic criteria for PBL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results A total of 300 patients with confirmed PBL were identified. The median age was 49. There was a male preponderance with M:F of 2.7. The median duration of symptoms before diagnosis was 1 month. PBL involved the H&N (39%), Lymph nodes (LN) (33%), GI tract (31%), bone marrow (17%), bones (14%), lungs and pleura (10%), skin (9%), spleen (7%), liver (6%), CNS (6%), and testes (2%). Constitutional symptoms were reported in 35%. Stage III/IV accounted for 51% of the cohort. Sixty-two percent were immunosuppressed, 47% due to HIV. While 58% were Kappa restricted, 40% were Lambda, and 2% null. The median OS and DFS of the whole group were 25 and 15 months, respectively. The involvement of BM (p<0.0001), liver (p=0.003), lungs/pleura (p<0.0001), and upper GI tract (0.001) was associated with worse OS. Moreover, CD4<100 (p=0.006), HHV8+ (p=0.02), EBER-negative (p=0.01), LDH>500 (p=0.04), and stage>2 (p<0.0001) were also associated with worse OS. PBL involving the H&N had better OS (p=0.0001). Though CNS involvement, presence of constitutional symptoms, and MYC+ had numerically worse OS, it did not reach statistical significance. Age, sex, light chain restriction, type of immunosuppression, other organ involvement, and other IHC phenotype did not impact OS. Compared to no treatment, chemotherapy and stem cell transplant had incrementally superior median OS (2 vs. 27 vs. NR months, p<0.0001). Frontline intensive chemotherapy yielded better OS than CHOP-like and myeloma regimens in decreasing order (p<0.0001). Patients who attained CR as their best response also had a superior median OS (p<0.0001). Conclusion This study presents clinicopathologic data from the largest pooled cohort of patients with PBL. It identifies the type of organ involvement, CD4 counts, EBER and HHV8 status, LDH levels, stage, type of therapy, and quality of response to treatment as critical determinants of OS.

Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Background Primary Cutaneous Diffuse Large B-cell Lymphoma-Leg Type (PCDLBCL-LT) is a rare but non-indolent subtype of B-cell lymphoma. While most of PCDLBCL-LT starts over the lower extremities, some cases may present at other cutaneous sites. The determinants of survival outcomes in this disease are not very well defined. Therefore, we conducted this pooled database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies that influence survival in this disease. Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 122 cases that fit the diagnostic criteria for PCDLBCL-LT. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS). Results A total of 122 patients with confirmed PCDLBCL-LT were identified. The median age was 76. There was a male preponderance with M:F of 2.4. Seventy-three percent involved the extremities. The median duration of symptoms before diagnosis was 3.5 months. Involvement of lymph nodes, bone marrow, bone, and CNS occurred in 11%, 3%, 4%, and 3%, respectively. Constitutional symptoms were reported in 5%. The median OS and DFS of the whole group were 39 and 32 months, respectively. Patients younger than 70 had better median DFS (NR vs. 24 months, p=0.02) with a non-significant better median OS. Lymph node involvement (18 vs. 45 months, p=0.006) and stage T3 compared to T1/T2 (16 vs. 41 months, p=0.006) were associated with worse OS. Sex, constitutional symptoms, IHC phenotype, extra-lymphatic/extra-cutaneous organ involvement, and histologic cutaneous patterns did not impact OS. Compared to no treatment, chemotherapy, XRT+/-surgery, and stem cell transplant had numerically better OS without reaching statistical significance (5 vs. 39 vs. 41 vs. NR months, p=0.15). Patients who attained CR as their best response also had a superior median OS compared to responses less than CR and non-responders (61 vs. 23 vs. 11 months, p<0.0001). Conclusion This study presents updated clinicopathologic data from a large, pooled cohort of patients with PCDLBCL-LT. It identifies age, lymph node involvement, T stage, type of therapy, and quality of response to treatment as critical determinants of OS.

Blastic Plasmacytoid Dendritic Cell Neoplasm Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy with a propensity for cutaneous involvement. This disorder has gone through many reiterations over the years, being classified initially as a blastic NK-cell lymphoma, then a subset of AML, and finally recognized as a unique myeloid neoplasm. However, due to the poor understanding and the rarity of the disease, varied treatment approaches have historically been implemented, and no optimal data or guidelines for managing BPDCN are available. Therefore, we conducted this pooled database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies that influence survival in this disease. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 273 cases that fit the diagnostic criteria for BPDCN. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 273 patients with confirmed BPDCN were identified. The median age was 61.5. There was a male preponderance with M:F of 2.4. The median duration of symptoms before diagnosis was 5 months. Eighty-one percent of patients presented with skin lesions, 65% of which were disseminated. Involvement of Lymph nodes (LN), bone marrow (BM), spleen, peripheral blood, and CNS occurred in 62%, 73%, 55%, 71%, and 57%. Constitutional symptoms were reported in 13%. The median OS and DFS of the whole group were 16 and 13 months, respectively. Patients younger than 60 had better median OS (30 vs. 10 months, p < 0.0001). The involvement of LN (p = 0.03), BM (p = 0.007), spleen (p = 0.02), and peripheral blood (p = 0.01) was associated with worse OS. Furthermore, disseminated skin involvement had worse OS than focal (p = 0.001). Though CNS involvement, presence of constitutional symptoms, elevated LDH, and TdT negative status had numerically worse OS, it did not reach statistical significance. Sex did not impact OS. Compared to no treatment, non-dose-intense chemotherapy, dose-intense chemotherapy, and stem cell transplant had incrementally superior OS (3 vs. 10 vs. 22 vs. 66 months, p < 0.0001). Patients who attained CR as their best response also had a superior median OS (26 vs. 5 months, p < 0.0001). Conclusions: This study presents updated clinicopathologic data from a large, pooled cohort of patients with BPDCN. It identifies age, organ involvement, type of therapy, and quality of response to treatment as critical determinants of OS.

Mast Cell Leukemia Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Background Mast cell leukemia (MstCL) is a rare but aggressive variant of systemic mastocytosis (SM) which is defined by the presence of >20% atypical mast cells in the bone marrow. It is further classified into leukemic and aleukemic variants based on the presence or absence of >10% atypical mast cells in the peripheral blood, respectively. There is a wide variation in treatment regimens used to treat MstCL. Despite this, the prognosis remains poor. The determinants of survival outcomes in this disease are not very well defined. Therefore, we conducted this pooled database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies that influence survival in this disease. Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 144 cases that fit the diagnostic criteria for MstCL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results A total of 144 patients with confirmed MstCL were identified. The median age was 58.5. There was a slight female preponderance with F:M of 1.2. The median duration of symptoms before diagnosis was 2 months. Involvement of lymph nodes, spleen, peripheral blood, skin, and CNS occurred in 17%, 44%, 23%, 13%, and 6%, respectively. Constitutional symptoms and hemophagocytosis occurred in 33% and 8% of the cases, respectively. The median OS and DFS of the whole group were 9 and 8 months, respectively. Patients younger than 55 had worse median OS (6 vs. 15 months, p=0.03). Hgb<10g/dl (p=0.0002), Platelets<100K (p=0.01), leukemic phase (p=0.02), and complex cytogenetics (p=0.02) were associated with worse OS. Furthermore, presence of hemophagocytosis had worse OS (p=0.06). Although the presence of constitutional symptoms, Tryptase>200, and KIT mutations other than D816V had numerically worse OS, they did not reach statistical significance. Sex, IHC phenotype, presence of concomitant malignancy, and type of organ involvement did not impact OS. Compared to no treatment, dose-intense chemotherapy, non-dose-intense chemotherapy, novel agents, and stem cell transplant had incrementally superior OS (2 vs. 7 vs. 15 vs. 15 vs. 23 months, p<0.0001). Patients who attained CR as their best response also had a superior median OS compared to responses less than CR and non-responders (NR vs. 29 vs. 8 months, p<0.0001). Conclusion This study presents updated clinicopathologic data from a large, pooled cohort of patients with MstCL. It identifies age, anemia, thrombocytopenia, leukemic presentation, complex cytogenetics, type of therapy, and quality of response to treatment as critical determinants of OS.

Histopathological and Immunohistochemical Prognostic Factors in High-Grade Non-Endometrioid Carcinomas of the Endometrium (HG-NECs): Is It Possible to Identify Subgroups at Increased Risk?

In the present study, potential histopathological and immunohistochemical prognostic markers were investigated. Consecutive cases of high-grade non-endometrioid carcinoma (HG-NEC) of the endometrium were considered. Each surgical specimen was routinely processed; the most significant block was selected for immunohistochemistry and tested for ER, PR, ki67, p53, E-cadherin, β-catenin, Bcl-2 and cyclin D1. For each immunomarker, the percentage of positive tumor cells was evaluated (%) and dichotomized as low and high according to the distribution in the study population. Follow-up was collected for disease-free survival (DFS) and overall survival (OS). Thirty-three cases were eligible: 19 resulted in FIGO I-II; 14 resulted in FIGO III-IV. Twelve patients suffered a recurrent disease (mean follow-up 24.6 months); 8 patients died of the disease (mean follow-up 26.6 months). Women with recurrent disease demonstrated a significantly higher Bcl2% (35.84 ± 30.96% vs. 8.09 ± 11.56%; p = 0.0032) while DOD patients had higher ki67% (75 ± 13.09% vs. 58.6 ± 19.97%; p = 0.033) and Bcl2% of border significance (34.37 ± 34.99% vs. 13 ± 17.97%; p = 0.078). As expected, FIGO III-IV had a worse DFS (HR = 3.34; 95% CI: 1.1-10.99; p = 0.034) and OS (HR = 5.19; 95% CI: 1.27-21.14; p = 0.0217). Bcl-2-high patients (Bcl2 > 10%) demonstrated a significantly worse DFS (HR = 9.11; 95% CI: 2.6-32.4; p = 0.0006) and OS (HR = 7.63; 95% CI: 1.7-34; p = 0.0084); moreover, PR low patients (PR ≤ 10%) had significantly worse DFS (HR = 3.74; 95% CI: 1.2-11.9; p = 0.02). HG-NEC represents a heterogeneous group of endometrial aggressive neoplasms with a worrisome prognosis, often at an advanced stage at presentation. Bcl-2 and PR may represent promising markers to identify a subgroup of patients having an even worse prognosis requiring a careful and close follow-up.

Thoracic SMARCA4-deficient cancer descriptors and clinicopathologic determinants of survival: Analysis of a pooled database.

9049 Background: Inactivation of SMARCA4, a catalytic subunit of the SWI/SNF complex, has been linked to high-grade aggressive cancers with poor prognoses. SMARCA4-deficient thoracic tumors (SDTT) can involve any part of the chest cavity, including the lungs, mediastinum, pleura, and chest wall. SDTT’s detailed clinical features and optimal treatment still need to be clarified. Therefore, we conducted this pooled database analysis to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect survival in this unique group of thoracic cancers. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 120 cases of SDTT. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 120 patients with confirmed SDTT were identified. The median age was 54, with a peak incidence between 56 and 68. There was a male preponderance with M:F of 3. The median duration of symptoms before diagnosis was 3.5 months. Patients presented with local disease in 11%, locally advanced in 21%, and metastases in 61%. The primary sites were the lungs (45%), mediastinum (42%), and pleura (13%). Common metastatic sites were bone (32%), adrenals (30%), liver (20%), Brain (20%), and lungs (18%). The median OS of the whole group was 6 months. Ninety percent of patients had a smoking history with a median of 26 pack-years. Histology comprised epithelioid/rhabdoid (79%) and carcinoma (adenocarcinoma, mucinous, and undifferentiated, 21%). Carcinomas had a better median OS than sarcomatous histology (11 vs. 6 months, p=0.03). Furthermore, early stages (N0/N1) had a superior median OS compared to advanced stages (N≥2, M+) (16 vs. 5 months, p=0.02). Compared to no treatment, local therapies (surgery (S) or radiation (RT)), combination chemotherapy (CT), and combined modalities (CT±S/RT) were statistically superior with a median OS of 1, 4, 6, and 11 months, respectively (p<0.0001). Further analysis revealed CT+S had superior median OS to CT+RT (16 vs. 9.5 months). Moreover, those with immune checkpoint inhibitors incorporated into their therapies had the best median OS outcomes (p<0.0001). Age, sex, primary site, and size did not impact OS. Conclusions: This study presents updated clinicopathologic data from a pooled cohort of patients with SDTT cancers. It identifies the histologic type, stage, and treatment approach as critical determinants of OS.

Histological and immunohistochemical prognostic factors of primary angiosarcoma.

Angiosarcoma is a malignant vascular endothelial neoplasm with various histological patterns. Despite its highly malignant potential, histological prognostic prediction has not been adopted for angiosarcoma. This study aimed to establish a method of predicting the prognosis of primary angiosarcoma. Formalin-fixed, paraffin-embedded samples from 104 primary angiosarcomas were prepared. All the cases were reviewed based on histological examinations with H&E staining. Because the French Fédération Nationale des Centres de Lutte Contre Le Cancer system (FNCLCC) is not adopted for angiosarcoma, we experimentally established a modified version of FNCLCC. Immunohistochemical staining for ERG, CD31, CD34, D2-40, HHV-8, p16, C-MYC, and p53 was performed. Fluorescence in situ hybridization (FISH) was performed for 31 cases to assay c-MYC gene amplification. Multivariate analysis revealed that age (> 70years old) (p = 0.0011), non-cutaneous angiosarcoma (p = 0.0265), metastasis on diagnosis (p < 0.0001), size ≥ 5cm (p = 0.0388), no taxane chemotherapy (p = 0.0388), strong nuclear atypia (p = 0.0087), and the presence of luminal structure in ≥ 50% of the tumor volume (p = 0.0009) were independent poor prognostic factors. Among angiosarcomas with luminal formation, mFNCLCC scores were significantly correlated with a poorer prognosis. The overexpression of p16 was associated with less luminal formation (p = 0.0192). Immunohistochemical analysis of C-MYC showed a moderate level of concordance with FISH (Kappa value = 0.45). This study suggested that luminal formation and nuclear atypia may be poor histological prognostic factors of angiosarcoma and that mFNCLCC would be useful for predicting the prognosis of angiosarcoma with luminal formation.

Molecular prognostic factors in colorectal cancer: 5-year follow-up.

Colorectal cancer (CRC) is a frequently diagnosed and lethal disease. The risk of developing CRC is determined by environmental and genetic factors. Surgical treatment is the main curative modality for patients with CRC up to stage III. In recent years, a special place has been given to biological agents used as targeted therapy following the genetic analysis of the tumor: Bevacizumab (Avastin), Cetuximab (Erbitux), Ziv-aflibercept (Zaltrap). We present a study based on 46 colorectal tumor resection specimens from patients operated for CRC in the Surgery Departments of the Emergency County Clinical Hospital of Craiova, Romania. Histopathological examination and immunohistochemistry staining of tissue sections were performed to determine the degree of aggressiveness. Using the Kaplan-Meier test, we calculated the correlation coefficient between survival time and immunohistochemical prognostic factors. The patients were followed for 60 months postoperatively.

Predictive Factors for Pediatric Craniopharyngioma Recurrence: An Extensive Narrative Review.

Despite being classified as benign tumors, craniopharyngiomas (CPs) are associated with significant morbidity and mortality due to their location, growth pattern, and tendency to recur. Two types can be identified depending on age distribution, morphology, and growth pattern, adamantinomatous and papillary. The adamantinomatous CP is one of the most frequently encountered central nervous system tumors in childhood. Our aim was to review the relevant literature to identify clinical, morphological, and immunohistochemical prognostic factors that have been implicated in childhood-onset CP recurrence. Lack of radical surgical removal of the primary tumor by an experienced neurosurgical team and radiotherapy after a subtotal excision has been proven to significantly increase the recurrence rate of CP. Other risk factors that have been consistently recognized in the literature include younger age at diagnosis (especially <5 years), larger tumor size at presentation, cystic appearance, difficult tumor location, and tight adherence to surrounding structures, as well as the histological presence of whorl-like arrays. In addition, several other risk factors have been studied, albeit with conflicting results, especially in the pediatric population. Identifying risk factors for CP recurrence is of utmost importance for the successful management of these patients in order to ultimately ensure the best prognosis.

Abstract 6750: Primary effusion lymphoma descriptors and clinicopathologic determinants of survival: Analysis of a pooled database

Abstract Background Primary effusion lymphoma (PEL) is a rare and aggressive type of B-cell non-Hodgkin lymphoma presenting primarily as lymphomatous effusions in body cavities and less often as solid extracavitary masses. It is typically associated with human herpesvirus 8 (HHV8) infection and occasionally with Epstein-Barr virus (EBV) co-infection. It is commonly seen in immunocompromised states, such as human immunodeficiency virus (HIV) infection, organ transplantation, immunosuppressive therapy, or advanced age. Due to our limited understanding of this disease, we conducted this pooled database analysis to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect survival in this rare and unique lymphoma subtype. Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 303 cases of PEL. All cases with an unequivocal expression of CD19 and CD20 expression were excluded. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Result A total of 304 patients with confirmed PEL were identified. The median age was 49, with a peak incidence between 42 and 56 years. There was a male preponderance with M:F of 10. The majority (71%) was associated with HIV infection, with a median CD4 count of 108. Sixty-eight percent were cavitary with the pleural, pericardial, and peritoneal cavities involved in 56%, 20%, and 30%. The median duration of symptoms before diagnosis was 1.5 months. Patients presented with constitutional symptoms, hepatosplenomegaly, lymphadenopathy, and bone marrow involvement in 31%, 10%, 20%, and 16%. The median OS of the whole group was 6.5 months. Presentation with constitutional symptoms (p=0.026), extracavitary/solid tumors (p=0.03), and normal platelet counts (p=0.04) were associated with better median OS. Cavitary disease with effusions restricted to the thoracic cavity had also better median OS (p&amp;lt;0.0001). PEL occurrence in the context of immunosuppression due to transplantation had poor median OS (p=0.004). While having Kaposi sarcoma tended to impact OS negatively (p=0.08), Castleman’s disease did not. Compared to no treatment, combination chemotherapy alone, chemotherapy with anti-retroviral therapy, and stem cell transplant were statistically superior with a median OS of 1.5, 8, 30, and 16 months, respectively (p&amp;lt;0.0001). Conclusion This study presents updated clinicopathologic data from a pooled cohort of patients with PEL. It identifies the type of clinical setting contributing to immunodeficiency, disease presentation, the primary location of cavitary disease, and treatment approach as key determinants of OS. Citation Format: Supriya Gupta, Christopher Graham, Philip A. Haddad. Primary effusion lymphoma descriptors and clinicopathologic determinants of survival: Analysis of a pooled database. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6750.

Abstract 6749: Histiocytic sarcoma descriptors and clinicopathologic determinants of survival: Analysis of a pooled database

Abstract Background Histiocytic sarcoma (HS) is an aggressive, rare malignant neoplasm of cells with histiocytic differentiation. It can occur de novo or develop in the context of other malignant disorders. HS can present as disseminated or localized lesions in the skin, lymphatics, gastrointestinal tract, central nervous system, or other organs. Little is known about factors that impact HS clinical outcomes. We conducted this pooled database analysis to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect survival in this rare histiocytic entity. Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 146 cases of HS. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results A total of 146 patients with confirmed HS were identified. The median age was 52, with bimodal peaks between 14-28 and 56-70 years. There was a male preponderance with M:F of 1.3. Primary sites of involvement were CNS (21%), GI(16%), soft tissues (12%), H&amp;N and bones (9% each), skin (8%), liver (7%), spleen (5%), lung (4%), and breast (1%). Lymphadenopathy and bone marrow (BM) were involved in 21% and 42%, respectively. Constitutional symptoms were present in 6%. The median size of the HS tumor was 4.45cm. The median OS of the whole group was 16 months. Age younger than 55 had better median OS (NR vs. 6 months, p=0.038). The primary site of involvement also impacted the median OS, where soft tissues and visceral disease had longer OS than those with CNS and spleno-lymphatic disease (60 vs. 7 vs. 6 months, p=0.03). Stage 1 disease had better median OS than stages 2-4 (p=0.06). Furthermore, unifocal had better median OS than multifocal/multicentric disease (60 vs. 9 months, p=0.007). The presence of inflammatory background positively impacted OS (p=0.01). Compared to no treatment, localized therapies such as surgery (S) and radiation therapy (RT), and systemic combination chemotherapy (CT) were statistically superior, with a median OS of 1, 204, and 21 months, respectively (p=0.003). With HS not amenable to complete resection, CT and CT+S were superior to RT+S (15 vs. 60 vs. 7 months, p=0.008). While BM involvement and size &amp;gt;10 cm were associated with worse OS, the latter did not reach statistical significance. There was no difference in median OS with respect to sex. Conclusion This study presents updated clinicopathologic data from a pooled cohort of patients with HS. It identifies age, the primary site of the disease, stage and extent of the disease, the inflammatory background status, and treatment approach as key determinants of OS. Citation Format: Dinesh Keerty, Philip A. Haddad. Histiocytic sarcoma descriptors and clinicopathologic determinants of survival: Analysis of a pooled database. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6749.

Epigenetics in Canine Mammary Tumors: Upregulation of miR-18a and miR-18b Oncogenes Is Associated with Decreased ERS1 Target mRNA Expression and ERα Immunoexpression in Highly Proliferating Carcinomas

The expression of miRNAs is one of the main epigenetic mechanisms responsible for the regulation of gene expression in mammals, and in cancer, miRNAs participate by regulating the expression of protein-coding cancer-associated genes. In canine mammary tumors (CMTs), the ESR1 gene encodes for ERα, and represents a major target gene for miR-18a and miR-18b, previously found to be overexpressed in mammary carcinomas. A loss in ERα expression in CMTs is commonly associated with poor prognosis, and it is noteworthy that the downregulation of the ESR1 would appear to be more epigenetic than genetic in nature. In this study, the expression of ESR1 mRNA in formalin-fixed, paraffin-embedded (FFPE) canine mammary tumors (CMTs) was evaluated and compared with the expression levels of miR18a and miR18b, both assessed via RT-qPCR. Furthermore, the possible correlation between the miRNA expression data and the immunohistochemical prognostic factors (ERα immunoexpression; Ki67 proliferative index) was explored. A total of twenty-six FFPE mammary samples were used, including 22 CMTs (7 benign; 15 malignant) and four control samples (three normal mammary glands and one case of lobular hyperplasia). The obtained results demonstrate that miR-18a and miR-18b are upregulated in malignant CMTs, negatively correlating with the expression of target ESR1 mRNA. Of note, the upregulation of miRNAs strictly reflects the progressive loss of ERα immunoexpression and increased tumor cell proliferation as measured using the Ki67 index. The results suggest a central role of miR-18a and miR-18b in the pathophysiology of canine mammary tumors as potential epigenetic mechanisms involved in ERα downregulation. Moreover, as miRNA expression reflects ERα protein status and a high proliferative index, miR-18a and miR-18b may represent promising biomarkers with prognostic value. More detailed investigations on a larger number of cases are needed to better understand the influence of these miRNAs in canine mammary tumors.

Clinicopathologic Determinants of Subcutaneous Panniculitis-like T-Cell Lymphoma (SPTCL) Clinical Outcomes: Analysis of a Pooled Database

Introduction Subcutaneous Panniculitis-like T-cell Lymphoma (SPTCL) is a rare subtype of extra-nodal Peripheral T-cell Lymphoma. SPTCL was initially described as an aggressive T-cell lymphoma frequently associated with hemophagocytic syndrome (HPS) and requiring aggressive multiagent chemotherapy. In 2005, this entity was restricted to SPTCL with αβ phenotype, a less aggressive entity compared to its γδ counterpart, currently known as primary cutaneous γδ T-cell lymphoma. We conducted this analysis to explore the determinants of clinical outcomes in this little-known subtype of Peripheral T-cell Lymphoma. Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 214 cases. Descriptive statistics were calculated. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS). Results A total of 214 patients with confirmed SPTCL diagnosis were identified. The median age was 34 years with a peak incidence between ages 13 and 26. There was a female predominance with F:M ratio of 1.7. Upon presentation, 12% had lymphadenopathy, 12% had hepatosplenomegaly, and 27% had bone marrow involvement. No extra-nodal or extra-cutaneous involvement were reported. The most common clinical presentations were nodular skin changes (87%) followed by constitutional symptoms (57%). Fifteen and ten percent of SPTCL patients had history of immune-deregulatory disorders and immunosuppressive therapies, respectively. HPS occurred in 24% of the cases. Fat necrosis and dermal involvement were noted in 9% and 17%. The median duration of symptoms prior to diagnosis was 4 months. Median DFS of the whole group was 60 months. While the median OS of the whole group was not reached, the mean overall survival was 73 months. OS was not impacted by sex, constitutional symptoms, immunocompromising factors, presence of lymphadenopathy, hepatosplenomegaly, or bone marrow involvement. OS was not impacted by histological or immunohistochemical features though there was a trend for better OS as well as DFS for TIA-1 expressors. OS and DFS declined as age increased from <19 to 20-39 and >40 years. HPS negatively impacted OS and DFS, but with borderline significance with the latter. Attaining complete remission positively impacted both OS and DFS. Stem cell transplant positively impacted OS and DFS, but with borderline significance with the former. Conclusions This study presents a comprehensive clinicopathologic data from a pooled cohort of patients with SPTCL. It describes the clinicopathologic features of SPTCL and identifies major clinical, immunohistochemical, and therapeutic modalities that are major determinants of OS and DFS in this rare disease.