When excluding all other diagnoses leaves you with three
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1 When excluding all other diagnoses leaves you with three A Case of Sarcoidosis-Lymphoma Syndrome with Idiopathic Thrombocytopenic Purpura Clark Cutrer, M.D.
2 Introduction: Sarcoidosis Noncaseating granulomas Other characteristic findings: erythema nodosum, lymphopenia, hypergammaglobulinemia, hypercalcemia, and elevated ACE Highly variable clinical course Diagnosis of exclusion Mainstay of therapy: steroids
3 Idiopathic Thrombocytopenic Purpura Autoantibodies against platelet antigens Diagnosis of exclusion Bone marrow: Normal cellularity w/ megakaryocyte hyperplasia Association between autoimmune disorders and lymphoproliferative disease
4 Hodgkin s Lymphoma» Fevers, chills, night sweats, weight loss» Mediastinal lymphadenopathy common» Reed-Sternberg cells» CD30, CD 15 +
5 Timeline of events March 2016 July 2016 (early) October 2015 February 2016 May 2016 May-July 2016 July 2016 (late) onset of symptoms 1st LN biopsy negative Onset of B symptoms: dx: ITP, sarcoidosis; 2nd LN biopsy/bmb neg worse B symptoms, Rheum consulted; long-term steroids Rheum, Heme, Pulm, GI f/u; steroid taper; ongoing concern for lymphoma B symptoms + N/V/D; C diff + (x2) CT CAP: worse LAD; final LN biopsy
6 Our Case: 1 st Encounter 23 year-old African American male presented with groin/abdominal pain and nausea/vomiting for 5 months Also c/o fevers, chills, night sweats, 14lb weight loss, and decreased appetite for 1 month Physical exam: Shivering, thin young male Tender in RLQ and right inguinal area Right inguinal fullness but no distinct/well-defined lymph node
7 Initial Work-up Severe thrombocytopenia and diffuse LAD Lymph node biopsy: noncaseating granulomas Bone marrow biopsy: megakaryocytic hyperplasia
8 What did we do for him? Diagnosis: sarcoidosis and ITP Treatment: oral steroids, IVIG, and romiplostim with improvement in symptoms and thrombocytopenia
9 Timeline of events March 2016 July 2016 (early) October 2015 February 2016 May 2016 May-July 2016 July 2016 (late) onset of symptoms 1st LN biopsy negative Onset of B symptoms: dx: ITP, sarcoidosis; 2nd LN biopsy/bmb neg worse B symptoms, Rheum consulted; long-term steroids Rheum, Heme, Pulm, GI f/u; steroid taper; ongoing concern for lymphoma B symptoms + N/V/D; C diff + (x2) CT CAP: worse LAD; final LN biopsy
10 Our Case: 2 nd Encounter Interim: Follow-up with Rheumatology, Pulmonology; started on long-term steroids; negative LN biopsy x2 Presented 3 months later with dyspnea on exertion, nausea, vomiting, and diarrhea Also noted 30lb weight loss and worsening fevers, chills, and night sweats
11 Additional Work-up and Management Remarkable Lab Work: WBC 7.1, H/H 9.6/30.4, MCV 80, Platelets 380 AG 19, Albumin 3 LDH 164, Procalcitonin 0.11, Ferritin HIV/CMV/Arbovirus/Histoplasma + C. diff PCR; + FOBT Consults: Hematology, Rheumatology Diagnosis: C. difficile colitis Treatment: PO Vancomycin and Metronidazole; restarted home Prednisone
12 Timeline of events March 2016 July 2016 (early) October 2015 February 2016 May 2016 May-July 2016 July 2016 (late) onset of symptoms 1st LN biopsy negative Onset of B symptoms: dx: ITP, sarcoidosis; 2nd LN biopsy/bmb neg worse B symptoms, Rheum consulted; long-term steroids Rheum, Heme, Pulm, GI f/u; steroid taper; ongoing concern for lymphoma B symptoms + N/V/D; C diff + (x2) CT CAP: worse LAD; final LN biopsy
13 Our Case: 3 rd Encounter Later that month re-presented with same symptoms Work-up: Labs: LDH 276, ESR 58, negative C. diff PCR CT C/A/P with worsening diffuse lymphadenopathy Mediastinal lymph node biopsy:
14 Diagnosis: Classical Hodgkins Lymphoma Lymphocytic Infiltrate Reed Sternberg Cells
15 So what happened next Treatment: 8 cycles of chemotherapy (BEACOPP) After 6 cycles, PET showed resolution of disease Received Brentuximab instead of Procarbazine or Bleomycin
16 Quick recap: Sarcoidosis-lymphoma syndrome Rare but well-documented (first in 1960s) Patients with sarcoidosis have x higher risk of developing lymphoma (Hodgkins and non-hodgkins). 3 important factors (Bichel and Brinker) ITP associated with lymphoma Hodgkins most common Severity of ITP correlates to severity of lymphoma ITP may be first presenting symptom of lymphoma
17 First Case Ever? Well described association between sarcoidosis and lymphoma; lymphoma and ITP No other literature reports ITP in the setting of sarcoid lymphoma syndrome.
18 Take home points» Well described association between autoimmune disorders and lymphoma (Hodgkins most common)» Sarcoidosis almost always precedes lymphoma» Negative lymph node biopsy does not rule out lymphoma
19 Lesson Learned: When it doesn t fit the script, the search you cannot quit!
20 Acknowledgements Hardik Sonani, MBBS Lauren WIlliamson, M.D. Venkataraman Palabindala, M.D. Carter Milner, M.D. Tejal Patel, M.D.
21 Questions????
22 References 1. Karakantza M, Matutes E, MacLennan K, O'Connor NT, Srivastava PC, Catovsky D. Association between sarcoidosis and lymphoma revisited. J Clin Pathol Mar;49(3): Brincker, H. (1992). "Interpretation of granulomatous lesions in malignancy." Acta Oncol 31(1): Brincker, H. and E. Wilbek (1974). "The incidence of malignant tumours in patients with respiratory sarcoidosis." Br J Cancer 29(3): Brincker H. The sarcoidosis-lymphoma syndrome. Br J Cancer Sep;54(3): Fink, K. and H. Al Mondhiry (1976). "Idiopathic thrombocytopenic purpura in lymphoma." Cancer 37(4): Anaya JM, Gómez L, Castiblanco J. Is there a common genetic basis for autoimmune diseases? Clin Dev Immunol 2006; 13: Trishna Goswami; Shahzad Siddique; Phillip Cohen; Bruce D. Cheson. The sarcoidosis lymphoma syndrome. Clin Lymphoma Myeloma. 2010;10(4): Medscape reference. 8. Bichel J, Brincker H. Treatment of pruritus in Hodgkin's disease and in reticulum cell sarcoma. Scand J Haematol 1965; 2: Brincker H. Coexistence of sarcoidosis and malignant disease: causality or coincidence? Sarcoidosis 1989; 6: Michael A Silverman, Gil Z Shlamovitz, Edward A Michelson, Idiopathic Thrombocytopenic Purpura, Updated: Jul 22, Medscape reference. 11. S.J. Bradley, G.V. Hudson, D.C. Linch. Idiopathic thrombocytopenic purpura in Hodgkin's disease: A report of eight cases. Clinical Oncology. Volume 5, Issue 6, 1993, Pages Fink. K., and Al-Xfondhiry, H.: Idiopathic thrombocytopenic purpura in lymphoma. Cancer 37: , Rudders, K. A, Aisenberg. A. C., and Schiller, A. L.: Hodgkin s disease presenting as idiopathic thrombocytopenic purpura. Cancer 30: , Henry Y. Dong, M.D., Ph.D., Nancy L. Harris, M.D., Frederic I. Preffer, Ph.D., Martha B. Pitman, M.D.: Retrospective Analysis of the Utility of Cytomorphology and Flow Cytometry Modern Pathology , 2001.
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