Morning Report 28 Agustus 2023-dr. RIA.pptx

MR Patologi Klinik

1. 1 Morning Report Multiple Myeloma (MM) as a Complication of HIV infection: A Case Report I Putu Yuda Prabawa Supervisor: dr. Pande Putu Ayu Patria Dewi , Sp.PK

2. 2 CASE PRESENTATION

3. 3 IDENTITY NAME : INSR GENDER : MALE AGE : 45 YEARS OLD MR : 23017917 ADDRESS : KARANGASEM WARD : TRIAGE INTERNA TC : 00.33 WITA CHIEF COMPLAIN T : BONE PAIN 3

4. 4 PRESENT MEDICAL HISTORY Patient referred from Balimed Karangasem Hospital with chief complaint bone pain. The patient felt this pain since April 2023. The pain felt like bitten and worsen if the bone being touched and a little bit better with pain killer. This pain made the patient cant walk by himself, and the pain felt worsen every day. The patient complains of nausea and vomiting . Every time he eats, the patient says he immediately vomits. The history of diarrhea was denied. The patient also said his body weight loss maybe around 10 kg in this 4 months. The patient also feel malaise and weak due to his condition. 4

5. 5 PRESENT MEDICAL HISTORY This patient also complaint about multiple lump in the head, left shoulder and right pelvis that had appeared since april 2023. The patient had a history of a lump that appeared initially behind the left ear , and at that time the lump was said to be only an enlarged lymph node, but the lump was already disappear. After that a lump appeared on the left shoulder, followed by a lump upper left head, and in the right pelvis which was felt to continue to grow and feel painful. Complaints of this lump were said to have been examined at orthopedic doctor in several hospitals, and the last plan is the patient referred to Prof. IGNG Ngurah hospital for further examination and therapy. The patient said that he can still urinate and defecate normally. 5

6. 6 PAST MEDICAL HISTORY Past Medical History HIV infection who has been treated with Tenofovir, Lamivudine, and Dolutegravir (TLD) for the past 1 year History of hypertension, diabetes, heart , kidney or any other chronic diseases were denied Family History There are history of HIV in his wife and child Social history Patient work as a farmer 6

7. 7 TIMELINE PATIENT HAD LUMP IN HIS LEFT PART OF HEAD AND RIGHT PELVIC START FEEL BONE PAIN AND THERE IS A LUMP IN HIS LEFT SHOULDER APRIL 2023 MEI 2023 5 TH JULY 2023 PATIENT HA S HISTORY HIV INFECTION 1 YEARS MRI FOLLOWEF BY BONE SURVEY 21 TH AUGUST 2023 PATIENT REFFERED TO PROF NGOERAH HOSPITAL 7

8. 8 PHYSICAL EXAMINATION LOC : E 4 V 5 M 6 APP : Moderately ILL BP : 120/80 mmHg PR : 100 times/minutes regular RR : 20 times/minutes TEMP : 36.5 O C SPO2 : 97% room air VAS : 3 /10 BW : 55 kg 8

9. 9 PHYSICAL EXAMINATION Head : Lump Regio Occipitalis Sinistra Diameter 8cm Eye : A nemis - / -, Ict erus -/- Neck : L ymphnode Enlargement (-), Candidiasis Oral (+) Thorax Heart Inspection : Intercostal Space (ICS) Unseen Palpation : Intercostal Space (ICS) Palpable a t 1 cm Medial Midclavicular Line ( MCL) ( S ), ICS V Percussion : Right Border : ICS 4 Parasternal Line (PSL) (D) Left Border : ICS 5 Midclavicular Line (S) Auscultation : S1 S2 Single, Regular, Murmur ( - ) Lung Inspection : Symmetric on Static And Dynamic Palpation : Vf N/N Percussion : Sonor / Sonor Auscultation : V es + / + , Rhonci - /-, Wheezing - / - +/+ - /- -/- +/+ -/- -/- 9

10. 10 PHYSICAL EXAMINATION Abdomen Inspection : D istended ( -) there is a lump in right pelvis diameter 10, solid consistency Auscultation : B owel sound ( + ) normal Palpation : Pain in epigastrial region , tenderness in right lower quadrant (RLQ) in lump area (+) , defans muscular (-) murphy sign (-) liver : Un palpable Spleen : U npalpable Percussion : Ty mp h ani, shifting dullness (-) traube space tympani, CVA tenderness (-/-) Extremities There is a lump in left humerus diameter 10 cm , solid consistency Warm +/+, E dema -/- +/+ - / - 10

11. LABORATORY 11 CBC 18/8/23 ( BaliMed Karangasem) 21/8/23 (Prof. Dr. IGNG Ngoerah Hospital) References (Prof. Dr. IGNG Ngoerah Hospital) WBC (10 3 / uL ) 8.41 9.37 4.10-11.00 Neu (10 3 / uL ) 5.98 6.99 2.50-7.50 Lym (10 3 / uL ) 2.14 1.68 1.00-4.00 Mon (10 3 / uL ) - 0.50 0.10-1.20 Eos (10 3 / uL ) - 0.19 0.00-0.50 Bas (10 3 / uL ) - 0.01 0.00-0.10 H emoglobin (g/dL) 10.20 10.50 13.50-17.50 H CT (%) 31.40 29.50 41.00-53.00 MCV ( fL ) 89.60 90.50 80.00-150.00 MCH ( pg ) 29.00 32.20 26.00-34.00 MCHC ( g / dL ) - 35.60 31-36 P L T (10 3 / uL ) 444 343 150-440 MPV ( fL ) - 8.20 6.80-10.0 NLR - 4.17 ≤ 3.13 Anemia Normochromic Normositer and High NLR

12. LABORATORY 12 C hemistry 18/8/23 ( BaliMed Karangasem ) 21/8/23 ( Prof. Dr. IGNG Ngoerah Hospital ) 22/8/23 ( Prof. Dr. IGNG Ngoerah Hospital ) 23/8/23 ( Prof. Dr. IGNG Ngoerah Hospital ) 25/8/23 ( Prof. Dr. IGNG Ngoerah Hospital ) 26/8/23 ( Prof. Dr. IGNG Ngoerah Hospital ) References (Prof. Dr. IGNG Ngoerah Hospital) AST/SGOT (U/L) - 29.00 - - - - < 34 ALT/SGPT (U/L) - 11.00 - - - - < 55 Calcium (mg/dL) - 16.30 15.40 15.70 15.70 17.60 8.80-10.20 pH - 7.41 - - - - 7.35-7.45 pCO2 ( mmHg ) - 37.00 - - - - 35.00-45.00 pO2 ( mmHg ) - 160.00 - - - - 80.00-100.00 BEecf ( mmol /L) - -1.1 - - - - -2 - 2 HCO3- ( mmol /L) - 23.50 - - - - 22.00-26.00 SO2c (%) - 99.00 - - - - 95.00-100.00 TCO2 ( mmol /L) - 24.60 - - - - 24.00-30.00 Na ( mmol /L) 131 126 - 127 132 123 136-145 K ( mmol /L) 4.62 3.88 - 3.62 3.74 4.86 3.50-5.10 Albumin (g/dL) - 3.20 - - - - 3.40-4.80 BUN (mg/dL) 117.70 48.30 - 45.70 43.30 48.40 8.90-20.60 Creatinine (mg/dL) 3.79 4.08 - 3.70 3.16 3.17 0.72-1.25 e -GFR - 16.53 - 18.61 22.52 22.43 ≥90 Blood Glucose ( mg / dL ) - 69 - - - - 70-140 Hyponatremia, Renal Insufficiency , Hypercalcemia , and Hypoglycemia

13. LABORATORY 13 Immunology 21/8/23 ( Prof. Dr. IGNG Ngoerah Hospital ) References (Prof. Dr. IGNG Ngoerah Hospital) HBsAg ( S /CO) Non Reactive Non-Reactive: <1.0 Reactive: ≥ 1.0 Anti HCV ( S /CO) Non Reactive Non-Reactive: <1.0 Reactive: ≥ 1.0 Gamma# ( g / dL ) 1.36 1.0-1.70 A / G # Ratio 0.95 - Interpretation Chronic Inflammatory Disorders - Total Protein ( g / dL ) 5.80 6.40-8.30 Albumin (% and #) 48.80 2.83 54.60-65.10 4.00-4.80 Alpha 1 (% and #) 6.60 0.38 2.50-4.50 0.20-0.30 Alpha 2 (% and #) 12.80 0.74 6.50-10.70 0.50-0.80 Beta 1 (% and #) 3.40 0.20 4.30-6.70 0.30-0.50 Beta 2 (% and #) 4.90 0.28 2.50-5.30 0.20-0.40 Gamma (% and #) 23.50 13.90-23.50

14. LABORATORY 14 Urinalysis 23/8/23 ( Prof. Dr. IGNG Ngoerah Hospital ) References (Prof. Dr. IGNG Ngoerah Hospital) Specific Gravity 1.080 1.003 - 1.035 Turbidity Clear pH 5.00 4.5 - 8 Leukocytes ( leuco / uL ) Negative Negative Nitrite Negative Negative Protein (1+) Negative Glucose Negative Negative Ketone Negative Negative Blood Negative Negative Urobilinogen Normal Normal Bilirubin Negative Negative Colour Clear Yellow p.yellow - yellow Sedimentary Leukocytes (HPF) 1 < 2 Sedimentary Erythrocytes (HPF) 20 < 2 Sedimentary Epithelial Cells (HPF) 1 < 1 Casts (HPF) 0.6 - Cylinder (µL) 2.27 < 2.25 Bacteria (µL) 11.50 < 26.4 Yeast Cell (HPF) 0.70 -

15. LABORATORY 15 CD4 and Esbach Protein 21/8/23 ( Prof. Dr. IGNG Ngoerah Hospital ) 22/8/23 ( Prof. Dr. IGNG Ngoerah Hospital ) References (Prof. Dr. IGNG Ngoerah Hospital) CD4 Absolute 281 - 404-1.612 CD4 (%) 15.59 - 33-58 CD8 Absolute (cells/ uL ) 884 - 220-1.129 CD8 (%) 49.06 - 13-39 Interpretation Low helper T lymphocyte count, normal suppressor T lymphocytes, low CD4:CD8 ratio - - Urine Volume (ml/24 hours) - 1.700 - Esbach Protein (g/L) - 0.2 - Protein Loss (g/24 hours) - 0.3 < 0.15 Low CD4:CD8 ratio

16. X-RAY HUMERUS AP/LAT (17/4/23) 16 Malalignment A permeative lytic lesion was seen on the left humerus, periosteal reaction (-), osteoid matrix (-) on the proximal metadiaphysis of the left humerus accompanied by a comminuted fracture of the left humerus 1/3 proximal, displacement (+) Normal bone trabeculation The gaps and joint surfaces are good No joint dislocation was seen Visible soft tissue swelling in the left shoulder region 1/3 proximal Impression: Permeative lytic lesion on the proximal metadiaphysis of the left humerus and a displaced comminuted fracture of the left humerus 1/3 proximal accompanied by surrounding soft tissue swelling, susp. secondary dd/ primary malignant bone tumor BONE DISEASE

17. THORAX-AP (21/8/23) 17 Soft tissue: no abnormalities seen Bones: multiple osteophytes appear on the CV thoracalis Sharp left right pleural sinus Diaphragm right left normal Trachea: lies in the middle, airway patent Cast : normal size and shape, CTR 38% Pulmo : no visible consolidation / nodules. Normal bronchovascular pattern Impression: - Cor and pulmo show no abnormalities - Thoracic spondylosis

18. SKULL-AP/LATERAL (22/8/23) 18 There are multiple osteolytic lesions on the calvaria No bone fractures/dislocations were seen Normal bone trabeculation Sutures and venous lakes look good The size and size of the sella turcica is normal No visible signs of increased ICT A soft tissue opacity was seen in the left parietal region which destroyed the calvaria in that region. Impression: - Multiple osteolytic lesions of the calvaria, susp. MBD - Susp. malignant soft tissue mass of the left parietal region which destroys the calvarial bone in that region BONE DISEASE

19. BLOOD SMEAR (21/8/23) (INTERNAL MEDICINE) 19 Rouleaux Positive

20. 20 ECG (16/8/23) SINUS RHYTHM: 101 BPM AXIS : NORMAL P WAVE: NORMAL PR INTERVAL 178 MS QRS DURATION: <120 MS R/S AT V1>1 SV1+RV5<35 MM ST-T CHANGES (-) CONCLUSION : NORMAL SINUS RHYTHM

21. PHYSICAL EXAMINATION 21

22. ASSESSMENT 22 Multiple Myeloma with HIV Stadium IV WHO on HAART Other Comorbidities 1. AKI dd ACKD ec susp renal on CKD ec MM - Hypercalcemia - Multiple bone lytic lesion - Mild Anemia NN - P athological fracture of left humerus - Compressive fracture T8,9,10 - perirenal dextra mass e.c extraosseous myeloma dd p rimer malignancy 2. Hypoglycaemia e.c susp Low intake 4. Cachexia related malignancy 5. Depression and anxiety

23. 23 THERAPY IVFD NaCl 0,9% loading 1500 cc continued by IVFD R ingerfundin 200 cc/hour (target urine production 100-150cc/hour) Nystatin Oral Drop 2 ml every 6 hours D rinking sugar water S oft diet 1900 kcal/day Paracetamol 1000 mg every 8 hours io D omperidon 10 mg every 8 hours io ARV TLD 1 tablet every 24 hours io Biphosphonate as requested by Hematology -Oncologist 23

24. 24 PLANNING PLANNING DIAGNOSIS Bone Marrow Aspiration (BMA) CD4 HIV RNA Upper Lower USG abdomen Urinalysis 24

25. 25 PLANNING MONITORING - Complaint And Vital Sign - Visual Analogue Scale (VAS) - Urine Production 24 hours - Calcium every 24 hours - Blood Sugar Nuchter (BSN)/Fasting Blood Glucose every 24 hours - BUN SC Na K every 48 hours 25

26. 26 LOC : E 4 V 5 M 6 APP : Moderately ILL BP : 120/70 mmHg PR : 102 times/minutes regular RR : 22 times/minutes TEMP : 36.9 O C SPO2 : 99% room air VAS : 2 /10 BW : 45 kg 26 LAST CONDITION (26/8/23)

27. 27 27 LAST CONDITION (26/8/23) Head : Lump Regio Occipitalis Sinistra Diameter 8cm Eye : A nemis - / -, Ict erus -/- Neck : L ymphnode Enlargement (-), Candidiasis Oral (+) Thorax Heart Inspection : Intercostal Space (ICS) Unseen Palpation : Intercostal Space (ICS) Palpable a t 1 cm Medial Midclavicular Line ( MCL) ( S ), ICS V Percussion : Right Border : ICS 4 Parasternal Line (PSL) (D) Left Border : ICS 5 Midclavicular Line (S) Auscultation : S1 S2 Single, Regular, Murmur ( - ) Lung Inspection : Symmetric on Static And Dynamic Palpation : Vf N/N Percussion : Sonor / Sonor Auscultation : V es + / + , Rhonci - /-, Wheezing - / - +/+ - /- -/- +/+ -/- -/-

28. 28 Abdomen Inspection : D istended ( -) there is a lump in right pelvis diameter 10, solid consistency Auscultation : B owel sound ( + ) normal Palpation : Pain in epigastrial region , tenderness in right lower quadrant (RLQ) in lump area (+) , defans muscular (-) murphy sign (-) liver : Un palpable Spleen : U npalpable Percussion : Ty mp h ani, shifting dullness (-) traube space tympani, CVA tenderness (-/-) Extremities There is a lump in left humerus diameter 10 cm , solid consistency Warm +/+, E dema -/- +/+ - / - 28 LAST CONDITION (26/8/23) (IW)

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54. IMWG CRITERIA 54

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60. Hiperkalsemia pada pasien MM : bone resorption due to an imbalance between osteoclast and osteoblast activity tumor-induced bone destruction  increased bone resorption by osteoclasts . Resorpsi tulang  extracellular calcium efflux Myeloma patients often have irreversible renal function impairment  kidney capacity to remove calcium load is exceeded  calcium increases

61. HIPOALBUMIN DAN MYELOMIC KIDNEY Hipoalbumin pada MM : malnutrisi , renal disfunction, liver disorder IL-6 negatively correlated with albumin levels ( IL-6 blocks albumin production ) In active MM patients, IL-6 levels are increased. Excessive IL-6 causes B cell maturation and proliferation  low albumin  indicates a more aggressive MM . (MYELOMIC KIDNEY) : The renal injury can be categorized into immunoglobulin ( Ig ) mediated , non- immunoglobulin ( Ig ) mediated , and glomerulonephritis (GN) . The most common renal injury is an immunoglobulin ( Ig ) mediated , which includes cast nephropathy ( also known as myeloma kidney ), monoclonal immunoglobulin deposition disease (MIDD), and light chain amyloidosis (AL). Non- immunoglobulin ( Ig ) mediated , include hypercalcemia , volume depletion , sepsis, tumor lysis , medication toxicity , and plasma cell invasion of the renal parenchyma . GN can present as membranoproliferative , crescentic , or cryoglobulinemia . Occasionally minimal change disease or membranous disease can also be seen .

62. Rouleaux in Myeloma These erythrocytes are grouped in “rouleaux,” a “stack-of-coins” pattern most often associated with elevated levels of immunoglobulin or fibrinogen. These positively-charged plasma proteins coat the negatively-charged surface of the erythrocytes, resulting in neutralization of the cells’ surface charge and enabling them to come together to form rouleaux. 62

63. Imunoglobulin terdiri dari 2 heavy chain dan 2 light chain Ada 5 tipe heavy chain : IgG, IgA, IgM, IgD , IgE Ada 2 tipe light chain : Kappa, Lambda. Sel plasma dibentuk di susum tulang  fungsi : membentuk antibodi (immunoglobulin, terutama IgA, IgG, IgM) untuk melawan infeksi bakteri dan virus. Normalnya , antibody yang terbentuk adalah polyclonal pattern. Antibodi akan melekat di protein permukaan bakteri / virus  memberikan signal ke sel imun lain untuk membunuh bakteri / virus Myeloma cell : kanker sel plasma  sel plasma membentuk antibody abnormal dalam jumlah besar yang sebenarnya tidak memiliki fungsi (no useful function) dan yang dibentuk biasanya hanya 1 jenis (monoclonal)  paraprotein / M-protein / monoclonal-protein Paraprotein dapat berupa : immunoglobulin intak , free light chain / heavy chain, fragmen immunoglobulin

64. Immunohistochemistry can detect plasma cells that express immunoglobulin in the cytoplasm and occasionally on the cell surface; myeloma cells are typically CD56, CD38, CD 138, CD319-positive , and CD19 and CD45-negative . Clonality is confirmed by kappa or lambda light chain restriction

65. Pathophysiology MM is thought to arise from a pre-malignant, asymptomatic phase of clonal plasma cell growth called monoclonal gammopathy of undetermined significance (MGUS). MGUS is defined as detecting monoclonal immunoglobulins in the blood or urine without evidence of end-organ damage. The exact causes of MGUS development and progression to MM remain unknown. However, as noted above, genetic alterations may cause an increased expression of promoter genes or resistance to apoptosis, both resulting in higher plasma cell proliferation and population. Under the "second hit" hypothesis, progression could also be a consequence of additional cytogenetic lesions gained by the original plasma cell clone, caused either by genetic instability or abnormalities in the hematopoietic microenvironment . The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of osteoclasts and suppression of osteoblasts , resulting in bone loss . 70 Albagoush SA, Shumway C, Azevedo AM. Multiple Myeloma . [ Updated 2023 Jan 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing ; 2023 Jan-.  Available from : https://www.ncbi.nlm.nih.gov/books/NBK534764/

66. Some people may over produce two different immunoglobulins eg. IgG Kappa and IgA Lambda. These are then measured as two different paraproteins and is referred to as bi-clonal myeloma. 71

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