Pediatrics | Eklavya Medical

lock Protected Clinical Document • Pulse App • Screenshots Strictly Prohibited

QUESTION 171 person Asked by .

bookmark_add

Q128. Neuroblastoma

collections Question Diagrams & Reference Images (1)

zoom_in View Image

description Clinical Response

Q128 ★ · DNB/MD 2022/1

Neuroblastoma

Examiner's Intent: Neuroblastoma is favorite given its striking clinical heterogeneity, directly explained by specific molecular risk factors; examiners expect the INRG risk stratification connected to this heterogeneity, and the specific diagnostic tests unique to this tumor type.

Clinical Presentation Based on Anatomical Site

Site	Presentation
Adrenal medulla (most common)	Abdominal mass, often massive; catecholamine excess only occasionally produces classic hyperadrenergic syndrome despite biochemically elevated metabolites
Paraspinal ganglia	“Dumbbell” tumor through neural foramina → spinal cord compression, neurological deficits — emergency
Cervical/thoracic sympathetic chain	Horner syndrome (ptosis, miosis, anhidrosis)
Metastatic	Bone marrow, bone (pain, limp), liver (esp. infant “Stage MS”), skin (bluish nodules in infants); periorbital ecchymosis (“raccoon eyes”) — orbital bone involvement

INRG Risk Stratification

Integrates: age at diagnosis (infants have better prognosis even with comparable extent), INRG stage, histopathology, and MYCN amplification status.

Distinctive Biology: Stage MS — metastatic disease confined to skin/liver/limited marrow, infants <18 months — paradoxically favorable with substantial spontaneous regression potential, despite being metastatic by conventional logic.

Diagnostic Workup

Test	Role
MIBG scan	Functional imaging via norepinephrine-analog uptake; basis for therapeutic 131-I-MIBG radiotherapy in relapsed/refractory disease
Urinary VMA/HVA	Elevated in most cases — diagnostic support + response/relapse monitoring
MYCN amplification	Single most important molecular prognostic marker — presence alone places patient in high-risk category regardless of stage

Multimodal Therapy

Risk Group	Treatment
Low-risk	Surgery alone, or observation (favorable Stage MS)
Intermediate-risk	Surgery + moderate-intensity chemotherapy
High-risk (incl. any MYCN-amplified)	Induction chemo + surgery + high-dose chemo with autologous stem cell rescue + radiotherapy + anti-GD2 immunotherapy (dinutuximab) + cytokine therapy + isotretinoin

lock Protected Clinical Document • Pulse App • Screenshots Strictly Prohibited

QUESTION 172 person Asked by .

bookmark_add

Q129. Wilms Tumor (Nephroblastoma)

collections Question Diagrams & Reference Images (1)

zoom_in View Image

description Clinical Response

Q129 · DNB/MD 2021/2

Wilms Tumor (Nephroblastoma)

Examiner's Intent: Expects clinical presentation, awareness of the two major differing staging philosophies (COG versus SIOP), and the critical prognostic significance of anaplasia on histopathology.

Clinical Features

Most common pediatric renal malignancy — classically asymptomatic abdominal mass, often incidentally discovered. May also present with abdominal pain, hematuria, hypertension (renin secretion/compression). Associated syndromes: WAGR (Wilms, Aniridia, Genitourinary anomalies, Range of developmental delay), Beckwith-Wiedemann syndrome, isolated hemihypertrophy — warrant screening ultrasound surveillance.

Staging Systems — COG versus SIOP

Approach	Region	Sequence	Rationale
COG	Predominantly North American	Upfront surgical resection → staging from surgical/pathological findings → risk-adapted adjuvant chemo ± RT	—
SIOP	Predominantly European	Pre-operative (neoadjuvant) chemotherapy first (presumptive imaging diagnosis) → delayed surgery	Reduces intraoperative tumor rupture risk by shrinking tumor first

Note: Both approaches show comparable overall survival — two differing, internationally accepted philosophies achieving broadly similar outcomes. Neither is simply “correct.”

Diagnostic Imaging

Abdominal ultrasound → CT/MRI abdomen (extent, renal vein/IVC tumor thrombus assessment) → CT chest (lung is most common metastasis site).

Histopathology — Favorable versus Unfavorable (Anaplastic) Histology

Key Prognostic Factor: Diffuse anaplasia is associated with substantially worse prognosis and mandates significantly more intensive treatment — can override an otherwise favorable clinical stage, analogous to MYCN amplification in neuroblastoma (Q128).

Management Summary

Radical nephrectomy (nephron-sparing for bilateral disease) + risk-adapted chemotherapy (vincristine + actinomycin-D for favorable histology; + doxorubicin for higher-stage/unfavorable histology) + radiotherapy for higher-stage/unfavorable histology. Among the highest survival rates of any pediatric solid malignancy.

lock Protected Clinical Document • Pulse App • Screenshots Strictly Prohibited

QUESTION 173 person Asked by .

bookmark_add

Q130. Hemophagocytic Lymphohistiocytosis (HLH)

collections Question Diagrams & Reference Images (1)

zoom_in View Image

description Clinical Response

Q130 ★ · DNB/MD 2021/1

Hemophagocytic Lymphohistiocytosis (HLH)

Examiner's Intent: HLH is critical, high-mortality-if-missed given its presentation overlaps substantially with sepsis; examiners expect the HLH-2004 criteria precisely, clear primary/secondary distinction, and specific treatment protocol knowledge.

Definition and the Diagnostic Challenge

Key Diagnostic Pitfall: HLH's presentation (fever, cytopenias, hepatosplenomegaly, multi-organ dysfunction) is substantially indistinguishable from severe sepsis at initial presentation — yet HLH requires immunosuppression while sepsis-directed immunosuppression would be actively harmful. Delayed recognition carries substantial mortality risk.

Primary versus Secondary HLH

Type	Basis	Typical Onset	Notes
Primary (Familial)	Inherited mutations in cytotoxic granule pathway genes (PRF1, UNC13D, etc.)	Infancy/early childhood	Often no obvious trigger; extremely high mortality without treatment/HSCT; strong relapse tendency
Secondary (incl. MAS)	No genetic cytotoxic defect; triggered by identifiable factor	Any age	EBV (classic trigger), malignancy (lymphomas), autoimmune/rheumatic disease (MAS — classically systemic JIA)

HLH-2004 Diagnostic Criteria

Molecular diagnosis, OR 5 of 8 criteria:

Fever
Splenomegaly
Cytopenias in ≥2 of 3 lineages (Hb <9 g/dL, platelets <100,000/µL, neutrophils <1000/µL)
Hypertriglyceridemia (≥3 mmol/L) and/or hypofibrinogenemia (≤1.5 g/L)
Hemophagocytosis in bone marrow, spleen, liver, or lymph node
Low or absent NK-cell activity
Ferritin ≥500 µg/L (markedly higher, e.g. >10,000, is highly suggestive with much better specificity)
Elevated soluble CD25 (soluble IL-2 receptor)

Treatment Protocol

Component	Role
HLH-94/HLH-2004 protocol (etoposide + dexamethasone; cyclosporine in continuation)	Standard backbone; bridge to HSCT for primary/familial HLH (only curative option)
Secondary HLH/MAS	Identify and treat the underlying trigger + immunosuppressive HLH-directed therapy
Emapalumab	Monoclonal antibody targeting interferon-gamma — for primary HLH refractory to conventional therapy

lock Protected Clinical Document • Pulse App • Screenshots Strictly Prohibited

QUESTION 174 person Asked by .

bookmark_add

Q131. Tumor Lysis Syndrome (TLS)

collections Question Diagrams & Reference Images (1)

zoom_in View Image

description Clinical Response

Q131 · DNB/MD 2020/2

Tumor Lysis Syndrome (TLS)

Examiner's Intent: Expects the Cairo-Bishop diagnostic definition, and clear prevention/management strategies including the specific distinction between rasburicase and allopurinol use.

Pathophysiology and Cairo-Bishop Definition

Massive, rapid tumor cell death (spontaneous or chemotherapy-precipitated) releases potassium, phosphate, and nucleic acids (metabolized to uric acid) faster than the kidneys can excrete them.

Laboratory TLS (≥2 within window: 3 days before to 7 days after cytotoxic therapy)	Threshold
Uric acid	≥8 mg/dL (or 25% increase)
Potassium	≥6 mmol/L (or 25% increase)
Phosphate	≥4.5 mg/dL (or 25% increase)
Calcium	≤7 mg/dL (or 25% decrease — falls via calcium-phosphate precipitation)

Clinical TLS = Laboratory TLS + at least one of: acute kidney injury, cardiac arrhythmia, seizure, or death.

High-Risk Malignancies

Bulky, rapidly-proliferating hematological malignancies — particularly Burkitt lymphoma, ALL (especially high presenting WBC), other high-grade lymphomas.

Prevention — The Cornerstone of Management

Measure	Details
Aggressive IV hydration	Before chemotherapy in high-risk patients
Rasburicase	Recombinant urate oxidase; preferred for high-risk patients; contraindicated in G6PD deficiency (hemolysis risk from H2O2 by-product)
Allopurinol	Xanthine oxidase inhibitor; prevents further uric acid formation (does not reduce existing uric acid); reserved for lower/intermediate-risk patients

Management of Established Metabolic Complications

Hyperkalemia — calcium gluconate, insulin-dextrose, salbutamol, potassium-binding resins, dialysis for refractory cases
Hyperphosphatemia — phosphate binders; avoid calcium supplementation unless symptomatic hypocalcemia (risk of further Ca-phosphate precipitation)
Renal replacement therapy — for severe, refractory electrolyte derangement or significant AKI

lock Protected Clinical Document • Pulse App • Screenshots Strictly Prohibited

QUESTION 175 person Asked by .

bookmark_add

Q132. Hodgkin & Non-Hodgkin Lymphoma

collections Question Diagrams & Reference Images (1)

zoom_in View Image

description Clinical Response

Q132 · DNB/MD 2020/1

Hodgkin & Non-Hodgkin Lymphoma

Examiner's Intent: Expects clear distinction between the two lymphoma categories' characteristic subtypes and staging systems, reflecting their genuinely different biological behavior and clinical management approaches.

Hodgkin Lymphoma — Histological Subtypes

Defined by Reed-Sternberg cells (“owl's eye” appearance) in a reactive inflammatory background.

Subtype	Notes
Nodular sclerosis	Most common in adolescents/young adults; generally favorable prognosis
Mixed cellularity	—
Lymphocyte-rich	—
Lymphocyte-depleted	Least common; less favorable; associated with advanced age/immunocompromise
Nodular Lymphocyte-Predominant HL	Distinct entity; lacks classic RS cells (“popcorn cells” instead); more indolent course

Pediatric Non-Hodgkin Lymphoma — Key Subtypes

Unlike adult NHL (dominated by indolent, lower-grade B-cell lymphomas), pediatric NHL is predominantly high-grade, rapidly-proliferating:

Burkitt lymphoma — highly aggressive; MYC translocation; particularly high TLS risk (Q131)
Lymphoblastic Lymphoma — biologically/clinically closely related to ALL (Q122) — essentially a nodal/mediastinal presentation of the same process
Diffuse Large B-Cell Lymphoma (DLBCL) — aggressive, somewhat less rapidly-proliferating

Staging Systems

System	Used For	Structure
Ann Arbor	Hodgkin lymphoma (and some NHL)	Stage I–IV based on nodal regions relative to diaphragm; A/B suffix for systemic “B symptoms”
St. Jude (Murphy)	Pediatric NHL specifically	Reflects NHL's greater propensity for early, widespread dissemination (marrow, CNS) vs Hodgkin's contiguous nodal spread

Risk-Adapted Chemotherapy

Hodgkin lymphoma treatment (combination chemo, RT used more selectively given long-term toxicity concerns) is generally less intensive than the aggressive, ALL-like/Burkitt-specific protocols required for high-grade pediatric NHL, which also require CNS-directed therapy and aggressive TLS prevention.

lock Protected Clinical Document • Pulse App • Screenshots Strictly Prohibited

QUESTION 176 person Asked by .

bookmark_add

Langerhans Cell Histiocytosis (LCH)

collections Question Diagrams & Reference Images (1)

zoom_in View Image

description Clinical Response

Q133 · DNB/MD 2019/2

Langerhans Cell Histiocytosis (LCH)

Examiner's Intent: Expects understanding of the single-versus-multisystem clinical spectrum, the concept of "risk organ" involvement determining treatment intensity, and the specific diagnostic immunohistochemical markers.

Clinical Spectrum

Clonal proliferation of pathological Langerhans-cell-derived dendritic cells — ranges from isolated single-system disease (single lytic bone lesion; isolated seborrheic-dermatitis-like skin rash in infants) to multisystem disease.

“Risk Organ” Involvement — The Central Prognostic Determinant

Central Framework: Recognized risk organs: liver, spleen, bone marrow (hematopoietic system). Involvement of any is associated with substantially worse prognosis and mandates more intensive treatment — analogous in its central role to MYCN amplification (Q128) and anaplasia (Q129).

Multisystem disease confined to “non-risk” organs (skin, bone, lymph nodes, isolated pituitary/CNS) carries a considerably more favorable prognosis despite multiple organs being involved.

Diabetes insipidus is a particularly important, relatively common complication (hypothalamic-pituitary infiltration) — can be presenting or evolve during the disease course.

Histopathology — CD1a and Langerin (CD207)

Diagnosis requires biopsy with immunohistochemistry positive for CD1a and Langerin (CD207) — Langerin reflects Birbeck granule formation.

Treatment Protocols

Category	Treatment
Single-system, single-site (bone/skin)	Local treatment (curettage, local steroid injection) or observation — spontaneous regression potential
Multisystem, no risk organ involvement	Standard systemic chemotherapy (vinblastine + prednisolone-based)
Multisystem WITH risk organ involvement	More intensive treatment; early treatment-response assessment carries substantial prognostic significance

lock Protected Clinical Document • Pulse App • Screenshots Strictly Prohibited

QUESTION 177 person Asked by .

bookmark_add

Hereditary Spherocytosis & Hemolytic Anemias

collections Question Diagrams & Reference Images (1)

zoom_in View Image

description Clinical Response

Q134 · DNB/MD 2019/1

Hereditary Spherocytosis & Hemolytic Anemias

Examiner's Intent: Expects the specific membrane protein defects, appropriate diagnostic tests (with attention to the shift toward newer testing modalities), splenectomy indications, and essential post-splenectomy infection prevention.

Membrane Defect

Mutations affecting red cell membrane cytoskeletal proteins — most commonly ankyrin and spectrin; less commonly band 3 and protein 4.2. Deficiency → progressive membrane surface area loss (vesiculation) → spherocytic shape with reduced surface-area-to-volume ratio → trapped/destroyed in splenic microcirculation → extravascular hemolysis.

Diagnostic Tests

Test	Method	Notes
Osmotic fragility test	Increased fragility/lysis in progressively hypotonic saline	Traditional; reduced sensitivity for mild cases, limited specificity
EMA binding test	Flow cytometry — measures dye binding to band 3 protein; reduced binding in HS	Newer, preferred, superior sensitivity/specificity; small sample needed

Indications for Splenectomy

Curative/near-curative (eliminates primary site of destruction). Recommended for moderate-to-severe hemolysis (significant anemia, recurrent symptomatic gallstones, growth impairment); mild, well-compensated disease may be observed. Generally deferred until age 5–6 years where feasible given young children's elevated OPSI risk.

Post-Splenectomy Infection Prevention

Measure	Details
Vaccination	Pneumococcal, meningococcal, Hib — ideally ≥2 weeks before elective splenectomy
Lifelong penicillin prophylaxis	Particularly emphasized in young children; some guidelines continue into adulthood for highest-risk patients
Patient/family education	Prompt medical attention for febrile illness — OPSI can progress rapidly to fatal sepsis

lock Protected Clinical Document • Pulse App • Screenshots Strictly Prohibited

QUESTION 178 person Asked by .

bookmark_add

G6PD Deficiency & Oxidative Hemolysis

description Clinical Response

Q135 · DNB/MD 2018/2

G6PD Deficiency & Oxidative Hemolysis

Examiner's Intent: Expects genetic basis, specific recognized triggers (of direct, practical clinical relevance), the important neonatal jaundice association, and correct diagnostic testing timing.

Genetics

X-linked — affected males (hemizygous) typically more severely/consistently affected; heterozygous female carriers show variable expressivity from random X-inactivation (lyonization).

Triggers for Acute Hemolytic Crises

G6PD deficiency impairs NADPH generation (pentose phosphate pathway) → reduced glutathione → vulnerability to oxidative stress.

Trigger	Examples
Medications	Primaquine and related 8-aminoquinolines (P. vivax radical cure — requires G6PD screening first), sulfonamides, nitrofurantoin, other oxidant drugs
Fava bean ingestion	Classic “favism” — certain Mediterranean/Middle Eastern variants particularly sensitive
Infection	Acute infectious illness alone can precipitate sufficient oxidative stress

Association with Neonatal Jaundice

Note: Important recognized cause of significant neonatal hyperbilirubinemia, sometimes with kernicterus risk — even modest, subclinical hemolysis can meaningfully contribute given the immature neonatal liver's limited conjugation capacity.

Diagnostic Screening Tests

Timing Pitfall: G6PD activity testing during/immediately after an acute hemolytic episode can be falsely normal — the most deficient (oldest) cells are preferentially destroyed, leaving a younger-cell-enriched population with relatively higher activity. Test should be deferred several weeks after full resolution.

Management

Remove offending trigger, supportive care (hydration, transfusion for severe anemia), monitor/manage hyperbilirubinemia (neonatal context: standard phototherapy/exchange transfusion principles). Long-term: patient/family education on trigger avoidance — no curative treatment for the enzymatic deficiency itself.

lock Protected Clinical Document • Pulse App • Screenshots Strictly Prohibited

QUESTION 179 person Asked by .

bookmark_add

Coagulation Cascade & Disseminated Intravascular Coagulation (DIC)

collections Question Diagrams & Reference Images (1)

zoom_in View Image

description Clinical Response

Q136 · DNB/MD 2017/2

Coagulation Cascade & Disseminated Intravascular Coagulation (DIC)

Examiner's Intent: Expects the standard laboratory panel for bleeding disorder evaluation and its interpretation pattern for DIC specifically, along with core management principles.

Laboratory Evaluation of Bleeding Disorders

Test	Assesses
PT	Extrinsic and common pathways
aPTT	Intrinsic and common pathways
Thrombin Time (TT)	Final fibrinogen-to-fibrin conversion; sensitive to fibrinogen abnormalities or circulating inhibitors (e.g., heparin)
Fibrinogen level	Quantitative fibrinogen
D-Dimer	Fibrin degradation product — reflects ongoing fibrinolysis of cross-linked fibrin

Pathophysiology and Management of DIC in Sepsis

Widespread, dysregulated coagulation activation, most commonly triggered by severe sepsis/septic shock (Section 2, Q23). Inflammatory/endothelial injury → widespread inappropriate coagulation → consumption of clotting factors/platelets (paradoxical bleeding tendency) + widespread microvascular thrombosis (end-organ dysfunction).

Laboratory Pattern: Characteristic pattern: prolonged PT/aPTT, low fibrinogen, thrombocytopenia, markedly elevated D-dimer — combined consumptive coagulopathy with ongoing fibrin formation/breakdown.

Management

Fundamentally: aggressive treatment of the underlying triggering condition (source control + antimicrobials) — DIC will not resolve without addressing the driver. Supportive blood product replacement: FFP (factor replacement), cryoprecipitate (significant hypofibrinogenemia), platelet transfusion (significant thrombocytopenia with bleeding/procedures) — a bridging, not definitive, role.

lock Protected Clinical Document • Pulse App • Screenshots Strictly Prohibited

QUESTION 180 person Asked by .

bookmark_add

Nutritional Anemias: B12 and Folate Deficiency

collections Question Diagrams & Reference Images (1)

zoom_in View Image

description Clinical Response

Q137 · DNB/MD 2016/1

Nutritional Anemias: B12 and Folate Deficiency

Examiner's Intent: Expects the shared megaloblastic mechanism, the critical distinguishing neurological feature of B12 (versus folate) deficiency, and appropriate diagnostic approach.

Shared Megaloblastic Mechanism

Both are essential cofactors for DNA synthesis (thymidylate synthesis) — deficiency impairs DNA synthesis while relatively sparing RNA/protein synthesis → nuclear-cytoplasmic maturation asynchrony → macrocytic anemia, hypersegmented neutrophils, megaloblastic marrow changes.

Neurological Manifestations — The Key B12-Specific Distinguishing Feature

Critical Clinical Pitfall: Only B12 deficiency, NOT folate deficiency, causes neurological manifestations — classically subacute combined degeneration (posterior column + lateral corticospinal tract demyelination), peripheral neuropathy, and in children, potential developmental regression. Folate supplementation alone can mask/correct the hematological picture of unrecognized concurrent B12 deficiency while neurological injury progresses unchecked.

Pediatric-Specific Context

In infants, B12 deficiency classically results from exclusive breastfeeding by a B12-deficient mother (strict vegan diet, unrecognized pernicious anemia/malabsorption) — presents with failure to thrive, developmental regression, irritability.

Diagnostic Workup

Serum B12 and folate levels
Serum methylmalonic acid (MMA) — elevated specifically in B12 (not folate) deficiency — confirmatory when serum B12 is borderline
Peripheral blood smear (macrocytosis, hypersegmented neutrophils)
Cause-directed evaluation (dietary history, maternal B12 status, malabsorption workup)

Q128. Neuroblastoma

Clinical Presentation Based on Anatomical Site

INRG Risk Stratification

Diagnostic Workup

Multimodal Therapy

Q129. Wilms Tumor (Nephroblastoma)

Clinical Features

Staging Systems — COG versus SIOP

Diagnostic Imaging

Histopathology — Favorable versus Unfavorable (Anaplastic) Histology

Management Summary

Q130. Hemophagocytic Lymphohistiocytosis (HLH)

Definition and the Diagnostic Challenge

Primary versus Secondary HLH

HLH-2004 Diagnostic Criteria

Treatment Protocol

Q131. Tumor Lysis Syndrome (TLS)

Pathophysiology and Cairo-Bishop Definition

High-Risk Malignancies

Prevention — The Cornerstone of Management

Management of Established Metabolic Complications

Q132. Hodgkin & Non-Hodgkin Lymphoma

Hodgkin Lymphoma — Histological Subtypes

Pediatric Non-Hodgkin Lymphoma — Key Subtypes

Staging Systems

Risk-Adapted Chemotherapy

Langerhans Cell Histiocytosis (LCH)

Clinical Spectrum

“Risk Organ” Involvement — The Central Prognostic Determinant

Histopathology — CD1a and Langerin (CD207)

Treatment Protocols

Hereditary Spherocytosis & Hemolytic Anemias

Membrane Defect

Diagnostic Tests

Indications for Splenectomy

Post-Splenectomy Infection Prevention

G6PD Deficiency & Oxidative Hemolysis

Genetics

Triggers for Acute Hemolytic Crises

Association with Neonatal Jaundice

Diagnostic Screening Tests

Management

Coagulation Cascade & Disseminated Intravascular Coagulation (DIC)

Laboratory Evaluation of Bleeding Disorders

Pathophysiology and Management of DIC in Sepsis

Management

Nutritional Anemias: B12 and Folate Deficiency

Shared Megaloblastic Mechanism

Neurological Manifestations — The Key B12-Specific Distinguishing Feature

Pediatric-Specific Context

Diagnostic Workup

Subcategory Tree

Category Subscription

Anatomical Models

Case Reviews