Project Title

In Situ Follicular Neoplasia yet another Spectrum That Extends From Normalcy to Overt Malignancy

Authors' Affiliations

Purva Sharma MD, Division of Oncology-Hematology, Quillen College of Medicine, East Tennessee State University. Bahaaeldin Youssef MD, Division of Pathology, East Tennessee State University Sakshi Singal MD, Division of Oncology-Hematology, Quillen College of Medicine, East Tennessee State University Devapiran Jaishankar MD, Division of Oncology-Hematology, Quillen College of Medicine, East Tennessee State University

Faculty Sponsor’s Department

Other - please list

Medical Oncology

Name of Project's Faculty Sponsor

Dr. Devapiran Jaishankar

Type

Poster: Competitive

Classification of First Author

Medical Resident or Clinical Fellow

Project's Category

Immune System, Lymphomas, Tumor Immunology

Abstract Text

In situ follicular neoplasia (ISFN) is defined as a monoclonal proliferation of B cells with immunophenotypic and genetic features of follicular lymphoma (FL) but confined to germinal centers of lymph nodes or other organs. It may not be associated with underlying overt lymphoma. It can be associated with lymphoproliferative disorders other than FL. A fifty-seven-year-old caucasian male initially presented with atypical chest pain, which led to cardiology evaluation. Patient underwent a coronary CT angiogram, which revealed a calcium score of 0, however also incidentally revealed mediastinal lymphadenopathy. Patient had a bronchoscopy which revealed no endobronchial lesions bilaterally. Using endo-bronchial ultrasound, right carinal lymph node was visualized, and trans-bronchial fine needle aspiration was performed. Cytology was positive for necrotic lesion with atypical cells. Patient had a dedicated CT scan of chest which showed enlarged sub-carinal lymph node measuring 3.3 x 3.0 cm. PET/CT scan showed increased uptake in the sub-carinal lymph nodes, also increased uptake of mid para-esophageal lymph nodes. It also showed some low-grade lymphadenopathy in right lower paratracheal region as well as mesenteric lymphadenopathy with misty appearance. Small pulmonary nodules were also noted in right middle and lower lobes with no associated uptake. Patient was scheduled for a mediastinoscopy and lymph node dissection. Patient proceeded with mediastinoscopy and a total of 4 lymph node specimens were removed from level 4R and level 7. Pathology from one of the lymph nodes revealed necrotizing granulomatous inflammation with staining consistent with histoplasmosis. Interestingly, two other lymph nodes showed in situ follicular neoplasia. Immunohistochemical stains demonstrated rare secondary lymphoid follicles with unremarkable morphology, showing strong germinal center staining with BCL2. FISH analysis was normal indicating absence of t(14;18). Pathology showed morphologically unremarkable B-cell nodules, concentrated in the cortical area which were CD20 positive and BCL2-positive. Patient underwent subsequent treatment with anti-fungal agents for the Histoplasmosis and is currently under surveillance for in-situ follicular lymphoma. In-situ follicular neoplasia is considered a premalignant lesion and a precursor of follicular lymphoma. Incidence of ISFN is difficult to ascertain, as it is usually a subclinical diagnosis. Incidence of FL is 3.18 per 100,000 population in the United States and findings suggest that ISFN is likely more frequent than that. Also, similar to FL, ISFN is seen in middle-aged and older individuals, mean age being around the fifth decade of life.Incidentally found ISFN without prior or simultaneous lymphoma is associated with a very low rate of clinical progression. Because some cases of ISFN are associated with prior or concurrent lymphoma, screening studies including computed tomography (CT) scan and bone marrow biopsy should be conducted after the diagnosis of ISFN is made. In the absence of overt lymphoma, it has been recommended that patients with ISFN be observed without chemotherapy, based on the very low incidence of progression into overt FL. The clinical significance of ISFN is not fully understood, however studies have demonstrated that incidentally found ISFN without prior or simultaneous lymphoma is associated with a very low rate of clinical progression. (

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In Situ Follicular Neoplasia yet another Spectrum That Extends From Normalcy to Overt Malignancy

In situ follicular neoplasia (ISFN) is defined as a monoclonal proliferation of B cells with immunophenotypic and genetic features of follicular lymphoma (FL) but confined to germinal centers of lymph nodes or other organs. It may not be associated with underlying overt lymphoma. It can be associated with lymphoproliferative disorders other than FL. A fifty-seven-year-old caucasian male initially presented with atypical chest pain, which led to cardiology evaluation. Patient underwent a coronary CT angiogram, which revealed a calcium score of 0, however also incidentally revealed mediastinal lymphadenopathy. Patient had a bronchoscopy which revealed no endobronchial lesions bilaterally. Using endo-bronchial ultrasound, right carinal lymph node was visualized, and trans-bronchial fine needle aspiration was performed. Cytology was positive for necrotic lesion with atypical cells. Patient had a dedicated CT scan of chest which showed enlarged sub-carinal lymph node measuring 3.3 x 3.0 cm. PET/CT scan showed increased uptake in the sub-carinal lymph nodes, also increased uptake of mid para-esophageal lymph nodes. It also showed some low-grade lymphadenopathy in right lower paratracheal region as well as mesenteric lymphadenopathy with misty appearance. Small pulmonary nodules were also noted in right middle and lower lobes with no associated uptake. Patient was scheduled for a mediastinoscopy and lymph node dissection. Patient proceeded with mediastinoscopy and a total of 4 lymph node specimens were removed from level 4R and level 7. Pathology from one of the lymph nodes revealed necrotizing granulomatous inflammation with staining consistent with histoplasmosis. Interestingly, two other lymph nodes showed in situ follicular neoplasia. Immunohistochemical stains demonstrated rare secondary lymphoid follicles with unremarkable morphology, showing strong germinal center staining with BCL2. FISH analysis was normal indicating absence of t(14;18). Pathology showed morphologically unremarkable B-cell nodules, concentrated in the cortical area which were CD20 positive and BCL2-positive. Patient underwent subsequent treatment with anti-fungal agents for the Histoplasmosis and is currently under surveillance for in-situ follicular lymphoma. In-situ follicular neoplasia is considered a premalignant lesion and a precursor of follicular lymphoma. Incidence of ISFN is difficult to ascertain, as it is usually a subclinical diagnosis. Incidence of FL is 3.18 per 100,000 population in the United States and findings suggest that ISFN is likely more frequent than that. Also, similar to FL, ISFN is seen in middle-aged and older individuals, mean age being around the fifth decade of life.Incidentally found ISFN without prior or simultaneous lymphoma is associated with a very low rate of clinical progression. Because some cases of ISFN are associated with prior or concurrent lymphoma, screening studies including computed tomography (CT) scan and bone marrow biopsy should be conducted after the diagnosis of ISFN is made. In the absence of overt lymphoma, it has been recommended that patients with ISFN be observed without chemotherapy, based on the very low incidence of progression into overt FL. The clinical significance of ISFN is not fully understood, however studies have demonstrated that incidentally found ISFN without prior or simultaneous lymphoma is associated with a very low rate of clinical progression. (