Why do I still have a bruise around my knee?

Abstract

Patient: A 45-year-old African-American female. Chief Complaint: The patient presented to the emergency department with the chief complaint of a bruise around her right knee, which occurred after a fall approximately 10 days prior to presentation. History of Present Illness: In addition to her persistent right knee bruise, she reported fatigue and shortness of breath after mild exertion of approximately 3 months' duration. Past Medical History: Non-smoker with no history of alcohol abuse and no chronic medical conditions. Physical Exam: Vital signs: temperature, 36.6°C; heart rate, 119 beats/minute; respiratory rate, 19 per minute; blood pressure, 122/66 mm Hg. Pertinent physical examination findings included labile mood, sinus tachycardia, conjunctival pallor, and hepatomegaly (liver span of 10 cm). Principal Laboratory Findings: See Table 1. The abnormal CBC and coagulopathy were of paramount concern and peripheral blood smear and mixing studies were performed. There was partial correction on mixing studies suggesting the presence of inhibitors. Peripheral Blood Smear Findings: Anemia, leukocytosis, thrombocytopenia with 28% atypical cells with basophilic cytoplasm and occasional eccentrically-placed nucleus with fine chromatin and nucleoli (Figure 1). Bone Marrow: Bone marrow aspirate and core biopsy demonstrated a hypercellular marrow diffusely infiltrated by blasts with irregular nuclear contour, basophilic cytoplasm, and prominent nucleoli (Figure 2). The CD138 immunohistochemical staining of the biopsy specimen highlighted the plasmablasts that are cytoplasmic kappa restricted (Figure 3A, 3B, and 3C). The Ki-67 (proliferation index marker) was approximately 5%. Flow Cytometry: Immunophenotypic analysis by flow cytometry demonstrated an abnormal plasma cell population expressing CD45 negative/CD19 negative/CD38 positive/CD138 positive/CD56 negative/kappa restricted immunophenotype (Figure 4). Cytogenetic Study: Three (20%) of the cells examined were normal. The remaining 80% exhibited complex aberrations and contained 78 to 90 chromosomes, with most cells in the 78 to 83 (hypertriploid) range. A composite karyotype of 12 cells was generated with the aid of interphase fluorescence in situ hybridization (FISH) studies using probes for IGH (14q32)/CCND1 (11q13), IGH/FGFR3 (4p16), IGH/MAF (16q23), TP53 (17p13.1), D13S319 (13q14.3), CEP 9 (9 centromere), CEP 15 (15 centromere), and D5S23/D5S721 (5p15.2), all from Vysis/Abbott Molecular (Des Plaines, IL). The karyotype, described with respect to triploidy, was: 78-90<3n>,XXX[12],+X[6], del(1)(p11p31)[12],der(?)t(1;?)(q12; ?)[6], +2[5],+3[11],+4[7],+6[2],i(6)(p10)[4], +7[7],+7[4],+add(7)(p12)[4],add(8)(q24.3)[12], +add(8)(q24.3) [11],+9[10],-10[3],+11[12], +11[3],+12[4],-13[12],-14[12],+15[2], -16[12],i(16)(p10)[9],dup(16)(q11.1q21)[8], del(17)(q11.2)[12],+del(17)(q11.2)[11], +der(17)t(1;17)(q21;q25) [3],+der(17)t(1;17)[3], +18[7],+18[3],+19[8],-20[12],+21[7],+?dup(21) (q22q22)[12],+?dup(21)[11],-22[6], +22[2],+1~10mar[cp12] (Fig 5A). Salient among the abnormalities were gains of chromosomes 3, 7, 9, 11, and 19; structural abnormalities of chromosome 1; and relative loss of chromosome 13. Notably, FISH analysis using the IGH/MAF probes was positive for translocation (Figure 5B). Additional Diagnostic Procedures: Computed tomography scan showed hepatomegaly and diffusely heterogeneous, moth-eaten appearance of the osseous structures with focal lytic lesions in T7 and L4 vertebral bodies (Figure 6). The echocardiogram showed normal cardiac function with an ejection fraction of 56%. Follow Up of this Patient: The patient was treated with bortezomib, a proteasome inhibitor, liposomal doxorubicin, and steroids. Her renal failure improved in concordance with improvement in primary disease and dialysis was prevented. She developed severe dilated cardiomyopathy (CMP) precluding further treatment with lisosomal doxorubicin. Fortunately, CMP reversed with time. She is currently doing well and awaiting definitive treatment definitive treatment while on a new treatment regimen that includes cyclophosphamide, etoposide, cisplatin, and bortezomib. Thalidomide was held after a single cycle due to grade 3 reversible neuropathy.