32yr old female with isolated splenomegaly and Pseudo Gaucher cells
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1 32yr old female with isolated splenomegaly and Pseudo Gaucher cells Swaminathan Murugappan MD, PhD Hematology Oncology Fellow University of Washington September 24, 2010
2 32yr old caucasian female presented to the SCCA hematology clinic in September 2009 for evaluation of her splenomegaly. 1. Left upper quadrant dull aching pain, constant with exacerbations. On going for a year. 2. Early satiety 3. Subjective fevers and chills 4. Night sweats requiring changing clothes at nights 5. Increasing fatigue and sleepiness pd weight gain in the last year (<10%) 7. Right metacarpophalangeal joint pain and stiffness for 3 weeks duration prior to her visit 8. History of frequent upper respiratory tract infections Pertinent negatives: 1. No other GI complaints or loss of apetite 2. No rash, recent travel or sick contact 3. No other joint involvement 4. No easy bruising or bleeding
3 Past Medical History 1. Splenomegaly of unknown etiology 2. Anxiety/Depression Social History: 1. Smoking: 20pk year history 2. Occasional alcohol intake 3. Single and works in an office based environment 4. No prior occupational exposure 5. No IVDA or any recreational drug use Family History: 1. Father and mother have diabetes mellitus 2. No known history of cancers Medications: 1. Zoloft 100mg daily 2. Percocet as needed for pain 3. OCP for menstrual pains
4 Physical Examination General: comfortable, no acute distress. AAO X 3. Vitals: Temp 36.9, HR 82, RR 16, BP 114/80, Ht 162 cm, Wt 92kg. HEENT: No pallor/icterus noted. Oropharynx was clear with no lesions. NECK: No lymphadenopathy or thyromegaly. CHEST: Clear to auscultation bilaterally. CVS: S1 and S2 heard. Regular rhythm without any murmurs, gallops, or rubs. ABD: Obese. Tenderness on deep palpation on the left upper quadrant. Spleen felt 5 cm below the costal margin. No hepatomegaly noted. EXT: No clubbing, cyanosis, or edema was noted. MSK: No joint swelling or tenderness or any evidence of muscle atrophy is noted. NEURO: Grossly intact. SKIN: No ecchymoses/rash were noted. LYMPH: No cervical, axillary or inguinal lymphadenopathy noted.
5 Outside laboratory data CBC March 2009: WBC 6.1, Hct 43, MCV 94 Platelet count 205. Normal differential counts. ESR March 2009: 12 Comprehensive metabolic panel including LFTs: Normal in March Thyroid function testing March 2009: Normal HIV and Hepatitis panel: Negative Outside radiological studies 1) Pelvic Ultrasound (02/23/09): Small uterine fibroid, splenomegaly 2) CT abdomen/pelvis with contrast (02/26/09): Enlarged spleen at 15X6X15cm. No adenopathy. Indistinct liver lesions too small to characterize. 3) Ultrasound Abdomen (03/2009): Splenomegaly 16.8 cm. Normal splenic vein flow. Outside pathology studies Bone marrow biopsy (03/2009): Reviewed at UW on 08/24/2009: Normocellular marrow with trilineage hematopoiesis and no evidence of dysplasia, leukemia, or lymphoma. Flow cytometry revealed no abnormal myeloid blast population or abnormal B, T, or NK cell population. Cytogenetic studies revealed a normal 46XX female karyotype
6 32yr old female with significant splenomegaly, constitutional symptoms, normal bone marrow and peripheral counts
7 Work-up at SCCA Labs (09/2009): WBC 8.12 Hct 43 MCV 93 Plt 188 Diff: ANC 4.39 Lymph 2.84 Mono 0.73 Eos 0.16 Baso 0.00 CMP: normal LDH: 149 Uric acid: 5.2 ESR: 6 CRP: 4.9 ANA: negative Blood cultures: No growth
8 Work-up (contd..) CT chest/abdomen/pelvis (09/2009): Slight interval decrease in size of spleen now measuring 15.0 cm craniocaudally x 7.7 cm transverse by 10.4 cm AP, previously measuring 15.8 cm cranial caudal x 8.2 cm transverse by 10.4 cm craniocaudal. No focal splenic lesion seen. (Compared to the outside films). Stable tiny 0.2 cm low attenuation lesion is seen in the dome of the liver, which is too small to characterize. No enlarged mediastinal, hilar, axillary lymph nodes, intra-abdominal nodes.
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10 Bone marrow biopsy 09/10/09 Bone marrow with maturing trilineage hematopoiesis and scattered and focally clustered, increased number of histiocytes most consistent with pseudo-gaucher cells. No histologic evidence of dysplasia, leukemia, lymphoma or abnormal plasma cells. Negative flow cytometry study for abnormal B, T, and plasma cells. Cytogenetics: 46XX.
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13 Workup so far. Infectious: Negative for bacterial, AFB, HIV, Hepatitis B/C infections. Rheumatological: Negative. Hematological: Unclear still with the presence of Pseudogaucher cells. Congestive: Unlikely, given the CT findings. Infiltrative: Not tested for Gauchers disease.
14 Clinical Course.. Patient remained symptomatic with significant effect on her quality of life. Tests for Gaucher s disease (peripheral blood leucocyte betaglucocerebrosidase activity) was normal. Based on patients preference and need for additional diagnostic specimen, laproscopic splenectomy was performed on October 8, Vaccinations were administered prior to surgery. Immediate post operative course was uncomplicated. Patient had significant improvement in her symptoms post surgery.
15 Spleen biopsy report.. 204g of aggregate of splenic tissue was received by Pathology. Splenic architecture was preserved. No infiltrating lymphoid collections noted. Significantly increased number of histiocytes containing bubbly cytoplasm present in the red pulp. Some of the macrophages also have refractile, pigmented material. Cells were PAS stain positive. Flow cytometry was negative for abnormal B or T cell population. Microbiological cultures for bacterial, AFB and fungal infections were negative. Final diagnosis: Splenic red pulp with increased histiocytes suggestive of reactive changes. Conferred with Dr. Elaine Jaffe at NIH.
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17 32yr old female with symptomatic splenomegaly, constitutional symptoms, normal blood counts now with evidence of reactive Pseudo-gaucher cells in the marrow and spleen
18 Clinical course.. Patient remained asymptomatic for 6 months until March Started developing similar LUQ pains along with fevers, chills and night sweats. Also reports weight gain. Repeat CT chest/abdomen/pelvis in March 2010 was unchanged. No new masses. LDH ranged from normal to 427. ESR was normal. CRP increased to 12.4 but returned to normal. ID and Rheumatology consulted and had a full workup done including fungal and viral studies. All the studies negative and no additional studies was recommended. She was diagnosed with fibromyalgia and started on antidepressants. Given the patient s symptoms from her underlying RES activation, she was started on prednisone 1mg/kg daily with a plan for slow taper.
19 Clinical course Patient responded to the steroids but had recurrent symptoms on the lower doses of steroids. Repeat CT studies in May 2010 showed an evolving chronic thrombosis of the anterior segmental and sub segmental branches of the right portal vein. This was apparently noted in the March 2010 CT but not reported. CT from Sept 2009 was reviewed and did not show any thrombus. USG showed that her portal vein flow was normal. PET CT looking for an inflammatory focus was negative. No anticoagulation was started given it was chronic of unclear duration with no RUQ symptoms/systemic clotting events. As of Aug 2010, she has been weaned off steroids and is under surveillance. Reportedly, she is asymptomatic without abdominal pains and other constitutional symptoms.
20 Key Questions. What is her primary diagnosis? Source of the pseudogauchers cells? Is the portal vein thrombus related to her laproscopic splenectomy or her underlying disorder? Additional diagnostic workup? Further treatment options, if her symptoms recur?
21 32yr old female with.. Diffuse splenomegaly Fevers, chills and night sweats Pseudo-gaucher cells in the marrow and spleen Portal vein thrombosis (post-surgical versus primary disorder driven) Normal peripheral blood counts
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23 Relative frequency of the causes of splenomegaly Liver disease (cirrhosis) 33% Heme Malig (Lymphomas) 27% Infection (AIDS, endocarditis) 23% Congestion or inflammation 8% Splenic vein thrombosis 4% Other/Unknown 5% West J Med 1998 Aug;169(2):88-97
24 Causes of massive splenomegaly (crossing the midline or in the pelvis) Chronic myeloid leukemia Myelofibrosis, idiopathic or post-polycythemic Gauchers disease Lymphoma, usually indolent, including hairy cell leukemia Kala-azar (visceral leishmaniasis) Tropical splenomegaly syndrome Thalassemia major AIDS with Mycobacterium avium complex Uptodate: Approach to adult patient with splenomegaly
25 CANCER June 1, 2001 / Volume 91 / Number 11 Splenectomies done between in Washington University and Brigham and Womens Hospital
26 CANCER June 1, 2001 / Volume 91 / Number 11
27 Lymphoma/Leukemia 57% Carcinoma 11% Cyst/Pseudocyst 9% Benign/Malig vascular lesions 7% CANCER June 1, 2001 / Volume 91 / Number 11
28 Pseudo gaucher cells Reactive histiocytes or macrophages that have an eccentric lobulated nucleus with a voluminous cytoplasm that as a crinkled paper appearance. Increased pseudo-gaucher cells probably reflects the increased load of leukocyte membrane-derived glucosylceramide presented to macrophages under conditions of high cell turnover when the normal pathways for its removal may be saturated. The cells are PAS stain positive but iron stain negative. This is in contrast to gaucher cells that is positive for PAS and iron.
29 Associations. MDS CML (multiple case reports) ALL Hodgkins lymphoma Non-Hodgkins lymphoma Thalassemia intermedia HbE disease Monoclonal gammopathy of unknown significance (MGUS) Multiple myeloma Sickle cell anemia Lymphoplasmacytic lymphoma Mycobacterial infections (Pubmed: Keyword Pseudo gaucher cells )
30 Portal Vein Thrombosis
31 Portal Vein Thrombosis
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34 8 patients with idiopathic SVT had JAK2 mutation. JAK2 mutation was not seen in any of the patients with DVT. These 8 patients had no etiology or other conventional thrombotic risk accounting for SVT. All of them had normal peripheral blood counts. However, all 8 patients had abnormal bone marrow biopsies with evidence for hyperplasia. 3/8 patient went on to develop overt MPD. One died of other causes. The remaining 2 patients still have normal counts. Given that there are JAK2 negative MPDs, all patients with idiopathic splenic vein thrombosis need bone marrow evaluation to assess for latent MPD.
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37 Comments and Questions.
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