Starr Morning Report Austin Akers, MD Internal Medicine PGY-3 - PowerPoint Presentation

Starr Morning Report Austin Akers, MDInternal MedicinePGY-3

Patient is a 59 year old previously fit and active male in remarkably good health for his age who has experienced a rapid overall physical decline over the last 2-3 months His chief complaint at presentation was new right-sided jaw/facial swelling and painInitial Presentation

Also describes progressively worsening fatigue, dyspnea, decreased exercise tolerate, intermittent confusion, headaches, abdominal pain, pain in his chest and back and a 25+ pound weight lossNo lifestyle changes, travel, new exposures or jobs during this time period or the months preceding symptom onset Initial Presentation (cont.)

PMH: HTN (successfully managed with diet and exercise)PSH:Right knee surgery in 1982Social Hx : 6 pack-year smoking history (quit >10 years ago) now smokes cigars a couple times per week Occasional marijuana use 2-3 beers per month Sexually monogamous with wife, no history of STDs No IVDAWorks out 4-6 times per week Past Medical/Surgical Hx

Medications:Aspirin 81 mg daily Occasional OTC Ibuprofen/TylenolAllergies:Iodinated contrastMedications/Allergies

Labs/Vitals CMP:GLU 137* BUN 18 CREA 2.50 * NA 136 K 4.1 CL 102 CO2 26 CA 13.5* TBIL 0.6 ALKP 89 SGOT 60 * SGPT 42 TPRO 12.1* ALB 3.1* BP: 136/62RR: 20T: 98.1 FP: 85 BPMSpO2: 96%Weight: 164 IbsBMI: 20.9 CBC: WBC 12.2* RBC 4.03* HGBAU 10.1* HCT 29.3* MCV 72.7* MCHC 34.5 RDW 13.2 PLT 204 MPV 10.4 PTH 6 (Low) Vitamin D 31 (WNL) Lactic acid 1.4 Troponin 0.01 UA noted moderate proteinuria

General:  A 59 y.o . male lying in the bed, no distress, appears somewhat cachecticHEENT: Head is normal cephalic, atraumatic. Sclera anicteric. Mucosa is pink and moist. Exophytic mass extending from alveolar ridge to lingular region of right mandible. Neck:  Right submandibular region with small mass and lymph nodes easily palpated. Heart:   CV is regular in rate and rhythm. No murmurs, gallops, or rubs. Chest:   Chest rise is symmetric on inspiration. Lungs clear to auscultation bilaterally to anterior and posterior lung fields. + tenderness to palpation of sternum and chest wall Abdomen:   Soft, nontender, non distended. Bowel sounds active and present x4.  No rebound tenderness, masses, or guarding.GU: Deferred. Extremities:  Extremities without clubbing, cyanosis, or edema. Skin: Warm, dry, and intact. No evidence of breakdown.Neurologic:  Cranial nerves II-XII grossly intact. Patient is alert and oriented to person and place, unsure of date. No focal deficits noted. Of note, tenderness to palpation of the mid and upper spine.Psychiatric: Normal mood and affect. Behavior is appropriate. Judgment and thought process appears to be intact. Physical Exam

Head, neck and chest imaging revealed a lytic, homogeneously enhancing mass of the right mandibular alveolar ridge with associated pathologic right submandibular lymph nodeIncidentally, lytic lesions of the skull, sternum and vertebral bodies were also noted Subsequent ENT biopsy of the mass revealed prominent, atypical plasma cells Workup/Imaging

SPEP and UPEP revealed a monoclonal protein spike in the gamma region with an IgG level of >6000 Bone marrow biopsy revealed hyper-cellular bone marrow with a significant Lambda-restricted plasma cell population accounting for at least 80% of the total nucleated bone marrow cells, findings consistent with myeloma Of note, at the time of initial presentation heme path review of his peripheral blood revealed significant rouleaux formation without plasma cells Workup/Imaging (cont.)

IgG lambda multiple myeloma, stage III“Mandibular mass as the primary manifestation of multiple myeloma” (http :// www.scielo.br/scielo.php?script=sci_arttext&pid=S1808-86942014000300266) Patient was treated with zoledronic acid, given a dexamethasone pulse and after being re-admitted for intractable pain was started on induction chemotherapy with Cyclophosphamide/ Bortezomib BUT WAIT , there’s more… Diagnosis

Late during the patient’s re-admission, he was noted to have 15% plasma cells on his CBC differential . Repeat heme path review now noted a few atypical plasma cells in the peripheral blood.Also during that admission an echo was obtained given the patient’s worsening SOB, mild pulmonary edema and the need for high volumes of fluid to be given with his chemo course TTE: EF 65% Estimated RVSP 70 Severely dilated RV, non-compressible IVC Primary team requested the patient remain in the hospital for further evaluation however the patient refused (what could go wrong?) Prior to discharge, a formal leukemia/lymphoma panel was obtained on the patient’s peripheral blood. The Plot Thickens…

The patient was subsequently admitted again one week later for a third time, this time for presumed LLL hospital-acquired pneumonia Labs on admission revealed acute liver failureINR 1.8TBILI 1.7AST 146ALT 200 A RUQ U/S revealed hepatomegaly of 20 cm at the mid-clavicular line (other liver workup unremarkable) Exam now showed significant JVD, a palpable thrill, hepatomegaly and new ascites. The patient now endorsed dyspnea with any activity beyond moving around in bed. Serum viscosity measured and was elevated Re-Re-Admission

In the span of several weeks we’ve gone from run of the mill multiple myeloma to new-onset pulmonary hypertension, liver failure and rapidly worsening functional status with plasma cells now seen on the peripheral smear.Now, remember that leukemia/lymphoma panel?“Population of circulating Lambda-restricted atypical plasma cells expressing CD138, CD38, CD56, and CD33 constituting 6% of circulating lymphocytes .” Non-diagnostic for acute plasma cell leukemia (OR IS IT?!?!) Lets Review

A spectrum of progressively more severe monoclonal gammopathies in which a clone or multiple clones of pre-malignant or malignant plasma cells over-produce and secrete into the blood stream a myeloma protein. An exception to the above definition is non-secretory multiple myeloma Plasma Cell Dyscrasias

Increased serum protein with an M spike on SPEP (<3 g/dL ) and clonal plasma cells comprising <10% of the bone marrow, however other features of MM are absent (lack of lytic lesions, hypercalcemia, Bence-Jones proteinuria, ETC.)Very common in elderly populations (5% in those 70+, estimated 15-20% of those 90+) Approximately 1% will progress to MM annually (i.e. most will never develop into myeloma) Considered “smoldering myeloma” when M protein >3 g/ dL or bone marrow plasma cells >10% but no myeloma-related symptoms or organ impairment (at this point much higher rate of progression to MM) MGUS

Diagnostic criteria for symptomatic myeloma (must meet all 3): Clonal plasma cells >10% on bone marrow biopsy A monoclonal protein in either serum or urine (except in cases of true non-secretory myeloma, about 3% of all myeloma), generally IgG or IgA Evidence of end-organ damage felt related to the plasma cell disorder (aka " CRAB“ signs/symptoms): Hyper C alcemia (corrected calcium >11 mg/dL)Renal insufficiency attributable to myelomaA nemia (hemoglobin <10 g/dl)Bone lesions on skeletal survey (generally lytic lesions however new osteoporosis with compressions fractures counts as well)Multiple Myeloma

Indolent non-Hodgkin lymphoma characterized by monoclonal IgM production Diagnostic criteria essentially the same as MM (Clonal plasma cells making up >10% of the bone marrow, M spike >3 g/dL, symptoms and/or organ dysfunction) however typically presents with more B-symptoms than the classical myeloma symptoms. Lytic lesions are absent.More highly associated with hyperviscosity syndrome (due to IgM simply being much larger than IgG or IgA). Visual and neurological deficits are classic. Waldenstrom Macroglobulinemia

Terminal stage and most aggressive form of the dyscrasias . Relatively rare, constituting only 2-4% of all plasma cell malignancies.May present as a primary plasma cell leukemia ( pPCL ), i.e. in patients without prior history of a plasma cell dyscrasia or as secondary plasma cell dyscrasia (sPCL ) , i.e. in patients previously diagnosed with a history multiple myeloma Prognosis is terminal and abysmal even with treatment, particularly for sPCL with a median survival of 2-6 months And yes, progression from MM to sPCL can be THAT rapid. The entire disease course from MGUS to MM to sPCL has been documented in under 6 months in some instances, though it generally is on the order of years.Plasma Cell Leukemia

1-4% of MM patients will progress to PCL with a median time being 21 months from first diagnosis These patients are HIGHLY symptomatic with a very rapid decline. Infiltration of solid organs with plasma cells can lead to organ failure.Classically >20% of nucleated blood cells being plasma cells has been the diagnostic criteria. This however is contested by many physicians and researchers in the field. Secondary PCL

Recently the International Myeloma Working Group has proposed a cutoff of >5% plasma cells in peripheral blood for diagnosis. This is based on data suggesting that prognosis worsens dramatically for myeloma patients above this value. In fact, prognosis appears to not vary much after the 5% cutoff (i.e. equally abysmal to the traditional cutoff). “Consensus Statement on Diagnostic Requirements, Response Criteria, and Treatment Recommendations by the International Myeloma Working Group (IMWG )” ( https ://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112539 / ) “Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition” (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451342/) Literature review

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451342 /https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112539/http:// www.scielo.br/scielo.php?script=sci_arttext&pid=S1808-86942014000300266 MKSAP UpToDate References

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