CASO CLÍNICO Nº 7

The patient is a 55-year-old white man who presents to the emergency department with chest pain and labored breathing. His temperature is 98.6° F. He is overweight and smokes two packs of cigarettes a day. His ECG and serum cardiac marker profile reveal changes compatible with an acute myocardial infarction. His complete blood count (CBC) shows the following:

Hemoglobin (Hb) 13 g/dL

White Blood Cells (WBC) 15,500/mm3

Platelets (Plt) 250,000/mm3

A differential white blood cell count was included in the CBC report, showing 80% segmented neutrophils (polymorphonuclear neutrophils), 10% band neutrophils, 7% lymphocytes, and 3% reactive lymphocytes.

What does the presence of neutrophilia indicate?

What is a "left shift," and what is its significance?

How may a leukemoid reaction be distinguished from chronic myelogenous leukemia?

CASO CLÍNICO Nº 8

First Presentation:

The patient is 47-year-old woman who presents to your office complaining of early satiety. She gives a history of a 5 to 10 pound unintentional weight loss. She notes associated night sweats and fevers up to 38ºC. Your physical examination demonstrates a woman in no acute distress. Her spleen is markedly enlarged, but no peripheral lymphadenopathy is noted.

The complete blood count (CBC) reveals:

Hemoglobin (Hb) 14.5 g/dL

White blood cells (WBC) 80,000/mm3

Platelets (Plt) 750,000/mm3

(Remember: mm3 = µL)

The patient was started on a treatment protocol of hydroxyurea at a dose of 20 mg/kg/day until her WBC count dropped to 10-20,000/µL.

Second Presentation (4 years later)

The patient presents with a one-month history of bone pain, weight loss, night sweats, fever, and early satiety. Physical exam reveals the reappearance of massive splenomegaly, and this time, lymphadenopathy as well.

Blood cytology reveals a predominance of lymphoblasts. Flow cytometric analysis identifies the majority of peripheral blood mononuclear cells as having the cell surface marker characteristics of B-lineage lymphoblasts [CD10+ (CALLA), κ immunoglobin light chain-, λ immunoglobin light chain-, TdT+, CD2−, CD7−, CD19+].

DNA samples isolated from peripheral blood from the first presentation and the second presentation were analyzed for immunoglobulin gene rearrangements by Southern blot analysis, demonstrating a clonally rearranged band in the second presentation sample but not in the first, raising the possibility of a second, independently arising tumor. However, Southern blot analysis of both of the samples with ABL probes and RT−PCR analysis with BCR and ABL primers indicate that both samples contain the same BCR-ABL rearrangement. Cytogenetic evaluation of bone marrow at the second presentation shows the t(9;22) translocation again, as well as additional chromosomal abnormalities typically seen in the blast phase of chronic myeloid leukemia.

1. Are these findings most consistent with a leukemic or a reactive process?

2. List some of the hematologic and clinical findings in this case that permit you to reach this conclusion.

3. What is the reason for this patient's early satiety and for her night sweats, fever, and weight loss?

4. What is the cytogenetic abnormality associated with this disorder?

5. How specific is this finding?

6. Is it found in other chronic myeloproliferative disorders?7. Does the presence of the Ph chromosome in ALL portend a good or bad prognosis?8. What is the molecular consequence of the t(9;22)?9. Do all cases of CML have a Ph chromosome?10. What is the prognosis of blast transformation of CML?11. What is the significance of the additional chromosomal abnormalities seen in the patient’s second

presentation?

CASO CLÍNICO Nº 19A 66-year-old man has noticed nontender enlarged lymph nodes in his neck and inguinal region of 5 months’ duration. He also tells you that he has lost 5 to 7 lb in the last 2 months. He denies fever or night sweats. His complete blood count (CBC) is unremarkable; specifically, his lymphocyte count is not elevated. Radiographic examination reveals retroperitoneal adenopathy. A large lymph node from the neck region is removed. Biopsy: Follicular lymphoma.

1. What characteristic cytogenetic abnormality is seen in follicular lymphoma?2. What is the molecular consequence of this translocation, and how may it relate to the pathogenesis and clinical

features of this disease?3. What is the prognosis of transformed follicular lymphoma?

CASO CLÍNICO Nº 20Paciente de sexo masculino de 28 años. Desde hace 3 meses presenta diaforesis nocturna ytos agregándose en las últimas 3 semanas, fiebre vespertina, hasta 38º C.2. Examen físicoPaciente normoconstituido, con buena coloración de piel y mucosa y estado de nutriciónnormal, boca y faringe normales. No existían adenopatías en regiones laterocervicales,supraclaviculares, axilares ni inguinales. La auscultación pulmonar era normal. Tonoscardiacos puros y rítmicos. Abdomen blando y depresible, sin visceromegalia.Extremidades normales.3. LaboratorioHemogramaHematocrito : 35 % Índice ictérico: < 5 UHemoglobina : 12,0 g/dL Reticulocitos :Glóbulos rojos: 4.100.000 /μL Leucocitos : 5.200 /μLCHCM : 34.3 % Plaquetas : 162.000 /μLVCM : 85.4 fL VHS : 52 mm/HrBasófilos EosinófilosSegmentados Linfocitos Monocitos0 1 75 18 6Glóbulos rojos : anisocitosis leveLeucocitos : normalesPlaquetas : normalesGlicemia 100 mg/dL (VN: 70-110 mg/dL)Nitrógeno ureico 14 mg/dL (VN: Hasta 20 mg/dL)Uricemia 3.8 mg/dL (VN: 2.4-5.7 mg/dL)Transaminasa glutámica oxalacética 25 U/L (VN: Hasta 40 U/L)Transaminasa glutámica pirúvica 26 U/L (VN: Hasta 40 U/L)Bilirrubina total 0.8 mg/dL (VN: 0.1-1.2 mg/dL)Bilirrubina directa 0.2 mg/dL (VN: 0-0.3 mg/dL)

Bilirrubina indirecta 0.6 mg/dL (VN: 0-0.9 mg/dL)Láctico deshidrogenasa 160 U/L (VN: Hasta 140 U/L)Proteína C reactiva 12 (VN: 0-1 mg/dL)

Orina completa: normalRadiografía de Tórax: ensanchamiento mediastínico suprahiliar derecho por posibleexistencia de adenopatías.TAC de tórax: Presencia de masa mediastínica, polilobulada, que ocupa el espacioretrocavopretraqueal con diámetro de hasta 12 cm.TAC abdomen y pelvis: NormalBiopsia de adenopatía mediastínica: ganglio linfático con alteración de su histoarquitectura dada por proliferación de ocasionales células de Reed – Sternberg (R-E), linfocitos y eosinófilos. Hay bandas de colágeno denso que dividen el tumor en nódulos. Se realizan estudios de inmunohistoquímica que muestra en las células tumorales (células R-E): CD 30+, CD15+, CD20 (-), CD3 (-).Biopsia Médula Ósea: Normal, sin infiltración por Linfoma.4. Diagnóstico: Sustente.

CASO CLÍNICO Nº 21

The patient is a 7-year-old boy who presents to your office complaining of easy fatigability. His mother also tells you that she has noticed that his gums bleed when he brushes his teeth. Physical exam fails to identify any specific abnormalities.

The complete blood count (CBC) reveals:

Hemoglobin (Hb) 10.5 g/dL

White Blood Cells (WBC) 75,000/mm3

Platelets (Plt) 25,000/mm3

You review the smear in the laboratory. A chest x-ray demonstrates a large mediastinal mass

This 10x magnification of peripheral blood demonstrates leukocytosis (reported count of 75,000/microliter).

Are these mononuclear cells blasts or reactive lymphocytes?

What differentiates lymphoblasts from mature (including reactive) lymphocytes?

How would you describe the cellularity and the cellular composition of the marrow biopsy specimen?

How can the leukemic blasts of ALL be distinguished from the myeloid blasts of AML?What prognostic features have been identified in ALL?Does this patient have a leukemic process or a T-cell lymphoma?Based on the clinical features of such patients, is it important to distinguish between these two processes?Based on the clinical and hematologic findings in this case, which CD antigens and cellular enzyme do you predict will be expressed by these cells?

CASO CLÍNICO Nº221.AntecedentesHombre de 56 años. Desde hace más de un año presenta dolor lumbar y cervical, sin otrasintomatología asociada. Desde hace un mes presenta dolor del tercio distal de brazoderecho que se agudiza con los movimientos y, al interrogatorio dirigido, refiere progresivo cansancio y fatigabilidad que antes no tenía. Por este motivo se realizó una radiografía encontrándose una lesión de aspecto tumoral. Los antecedentes familiares y personales carecen de interés.2. Examen físico

Enfermo con buen estado nutricional y leve palidez mucocutánea. Pares craneales, boca yfaringe normales. Ausencia de adenopatías periféricas. Auscultación cardiopulmonarnormal. Abdomen blando y depresible, sin visceromegalias. Brazo derecho intensamentedoloroso con cualquier tipo de movimiento, aunque los reflejos y la sensibilidad estánconservados.3. LaboratorioHemogramaHematocrito : 26 % I. Ictérico : < 5 UGlóbulos rojos: 3.100.000 /μL Leucocitos : 9.500 /μLHemoglobina : 8.6 g/dL Plaquetas : 200.000 /μLCHCM : 33.1 %VCM : 83.8 fL VHS : 110 mm/HrBasófilos Eosinófilos Segmentados Linfocitos Monocitos0 1 67 24 7Glóbulos rojos: Anisocitosis leve. Tendencia a la aglutinación y formación de Rouleaux.Leucocitos : Normales.Plaquetas : Normales.Transaminasa Glutámico Oxaloacética : 25 U (VN: hasta 40 U/L)Transaminasa Glutámico Pirúvica : 30 U (VN: hasta 40 U/L)Fosfatasa alcalina : 55 U (VN: 30-110 U/L)Bilirrubina directa : 0.3 mg/dL (VN: 0-0.3 mg/dL)Bilirrubina indirecta : 0.5 mg/dL (VN: 0-0.9 mg/dL)Bilirrubina total : 0.8 mg/dL (VN: hasta 1mg/dL)TTPA : 39 seg (VN: 35 – 45 seg)TP : 12 seg (VN: 11 - 13 seg)Nitrógeno ureico : 10.5 mg/dL (VN: 8-20 mg/dL)Creatinina : 0,8 mg/dL (VN: 0.7-1.3 mg/dL)Electroforesis de proteínas séricas: Se observa componente monoclonal en región de las γglobulinasInmunoelectroforesis: En suero y orina se confirma el componente monoclonal,detectándose que se trata de IgG (cadenas pesadas γ) con cadenas livianas kappa (κ)Cuantificación de inmunoglobulinas: IgG: 4.200 mg/dl (VN: 800-1600 mg/dL), IgM: 60mg/dL (VN: 50-200 mg/dL) y IgA: 110 mg/dL (VN: 140-400 mg/dL).Mielograma: médula ósea levemente hipercelular. Serie granulocítica levementedisminuida, serie eritroblástica moderadamente disminuida y serie megacariocíticaconservada. Células plasmáticas 55%, entre éstas se observan, células multinucleadas yotras de aspecto inmaduro.Radiografías: Tórax, abdomen y pelvis, normales. Presencia de abundantes lesiones líticasen la radiografía de cráneo. Aplastamiento vertebral de la primera lumbar. En la radiografíade húmero derecho se observa una lesión lítica de 3 cm de diámetro, a la altura del terciodistal.4.Diagnóstico: Sustente