Manuscript received: 13th Aug 2013, Reviewed: 26th Aug 2013
Author Corrected: 19th Sep 2013, Accepted for Publication: 30th Sep 2013
Case report
A 55 year female presented to outpatient Department with severe back pain, for last 3 months, along with weakness, fatigue, exertional dyspnoea for last 2 month. There was no history of trauma to trigger her back pain or any limb weakness. History of contact with Tuberculosis was negative. She had one episode of hemetemesis 15 days back. Her past history was unremarkable. She never received any chemotherapy or radiation exposure. Physical examination revealed severe pallor, mild icterus, and bilateral pitting edema. No lymphadenopathy, clubbing or petechiae/purpura was noted. Chest examination was normal. Spleen was palpable 2cm below left costal margin, non tender. Lab investigations Includes: Hb-45g/l, PCV-16.2%, TLC-8400/cu mm, N-56%, L-26% , PLT-32000/cu mm, ESR-93mm/1st hr. Peripheral Blood Smear examination showed mixture of Normocytic, Normochromic RBCs and Microcytic, Hypochromic RBCs, anisocytosis, polychromasia, few tear drop cells, schistocytes, nucleated RBCs(16/100WBCs). Reticulocyte count was 16.9%. Renal function test, Electrolyte and Calcium/ Phospahte levels were within Normal limit. Presence of DIC was ruled out as PT, INR, APTT were normal. Total bilirubin-3.1mg/dl, unconjugated fraction-2.2 mg/dl, conjugated fraction-0.9 mg/dl, SGOT-37U/L, SGPT-54U/L, ALP-3636U/L, GGT-36U/L suggesting bone origin of the raised ALP. Other investigations included LDH -699U/L, Uric acid-9.8 mg/dl, serum haptoglobin-0.08mg/dl. The blood picture established the presence of Microangiopathic Hemolytic Anemia.
Results of other investigation concluded following results. ECG-sinus tachycardia, CXR- Cardiomegaly & increased bronchovascular markings. USG - mild splenomegaly. Hb electrophoresis, serum ceruloplasmin was normal, direct and indirect Coomb’s test was negative, ANA-negative. As bone marrow aspiration resulted dry tap, BM biopsy was done. Upper GI Endoscopy has shown presence of antral solitary gastric ulcer from where biopsy was taken for histopathology.
Bone trephine biopsy: Reactive erythroid and megakaryocytic hyperplasia in some places and secondary myelofibrosis in other places. A search for malignancy was made for which CT thorax and abdomen was ordered.
Fig 1-figure of bone marrow trephine biopsy showing myelofibrosis.
CT scan thorax and abdomen: has shown focal left pleural thickening, lytic destruction of D9 and D10 vertebrae with prevertebral mass. CT guided FNAC was suggestive of osteosclerosis.
Fig 2- showing lytic destruction of dorsal vertebrae
MRI dorsal spine showed patchy areas of altered marrow signal intensity, showing heterogenous contrast, enhancement involving the bodies and posterior element of multiple dorsal vertebrae-suggestive of marrow infiltrative disorder.
Figure 3: MRI spine showing diffuse vertebral destruction at multiple levels.
Patient continued to have a downhill course inspite of being administered supportive treatment including blood transfusions. Finally the gastric ulcer HPE report reached us which showed presence of poorly differentiated Adenocarcinoma. Patient expired within 2 days after another bout of massive hemetemesis.
Fig 4: showing gastric adenocarcinoma in the HPE of gastric ulcer
Discussion
Microangiopathic hemolytic anemia can occur as a paraneoplastic syndrome in cancer patients, and it may present as the first manifestation. The most common tumors associated with MAHA are gastric, breast, and lung cancers [1-3]. A Korean study reported that 14 (25.5%) out of 55 MAHA patients had gastric cancer [3]. Cancer-associated MAHA (CA-MAHA) is a rare and fatal complication of malignant tumors. Most CA-MAHA patients die within a few weeks after the diagnosis, and the most common cause of death is infection [4]. Our patient died within 4 weeks. On average, the median time interval between the initial diagnosis of MAHA and the diagnosis of underlying malignancy is 6 days. Bone marrow examinations and bone scans are usually performed to detect CA-MAHA [5]. Our patient was diagnosed with CA-MAHA on the basis of the findings of bone marrow examination and histopathological examination of gastric ulcer although several studies have suggested that fibrinoid necrosis of the bone marrow and tumor cell emboli of the arteries, arterioles, and capillaries are the causes of CA-MAHA, its pathogenesis remains unclear6. Tumour-derived factors, procoagulants, decrease in von Willebrand factor (vWF)-cleaving protease ADAMTS13 play a role in CA-MAHA [6]. Bone metastases tend to occur in invasive cancers like Bormann types III and IV. Examination of the histology has shown that more than 80% of bone metastasis from gastric cancer was poorly differentiated adenocarcinoma. Thoracic and lumbar vertebrae are the most frequent sites of bone metastasis [7] although there are reported cases of deposits in pelvis [8]. Patients with bone metastases have mean survival times of less than 5 months with the longest survival period reported being 3 years [6]. Bone pain and respiratory symptoms are observed more frequently in CA-MAHA than in non-CA-MAHA [7]. Our patient experienced bone pain and dyspnea. There is no definitive treatment of choice for CA-MAHA. The low platelet count and hemoglobin level make red blood cell and platelet transfusion obligatory. Chemotherapy is the most reliable treatment of choice for the underlying cancer1.
Funding: Nil
Conflict of interest: Nil
Permission from IRB: Yes
References
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