Miss Diya, an 11-year-old female child, 1st order offspring born of a non-consanguineous marriage from Chandigarh, Punjab, presented with complaints of a painless, progressively enlarging swelling on the right side of her neck for 8 weeks, recurrent high-grade fever spiking up to $103^\circ\text{F}$ for 5 to 7 days alternating with afebrile periods of 1 to 2 weeks for the past 6 weeks, drenching night sweats requiring changing of clothes for 4 weeks, an unintentional weight loss of 4 kg ($>10\%$ of body weight), and a persistent dry brassy cough for 2 weeks, in the absence of contact with tuberculosis, sore throat, or ear discharge.

HOPI

The history dates back to 8 weeks ago when the mother first noticed a firm, non-tender lump situated in the right lower neck and supraclavicular fossa.

• Painless Cervical & Supraclavicular Swelling:
  • Insidious onset, noted 8 weeks ago; painless and slowly expanding.
  • Not associated with toothache, pharyngitis, skin boils, or discharge.
  • Overlying skin has remained entirely normal without redness or warmth.
• The Classical 'Pel-Ebstein' Fever Pattern:
  • Appeared 6 weeks ago; child experiences high-grade fever ($102-103^\circ\text{F}$) for 5 to 7 consecutive days, followed by complete spontaneous defervescence with normal temperature for 10 to 14 days, after which the fever paroxysm repeats cyclically.
• Drenching Night Sweats:
  • Mother reports that for the past 4 weeks, the child wakes up at night soaking in perspiration, necessitating changing her nightclothes and pillow cover, even with the air conditioner running.
• Weight Loss:
  • Measured weight dropped from 34.0 kg to 30.0 kg over the past 2 months (Loss of 4.0 kg = $11.7\%$ body weight loss $\to$ Confirms B-Symptom).
• Mediastinal Compression Symptoms:
  • Developed a dry, hacking, brassy cough 2 weeks ago, especially when lying flat at night.
  • Prefers sleeping propped up on two pillows; no stridor, hoarseness, or bluish facial discoloration.
• Negative Inquiries:
  • No history of contact with an adult pulmonary tuberculosis patient.
  • No history of unpasteurized milk consumption or cat scratches (Bartonella).
  • No bone pain, petechiae, or joint swellings.

Past history

• No history of prior lymph node biopsies, tuberculosis treatment, or immunosuppressive therapy.
• No history of recurrent sinopulmonary infections in early childhood.

Antenatal, natal and postnatal history

• Born at full term by normal delivery; uneventful perinatal period; birth weight 2.9 kg.

Development history

• Normal developmental milestones; currently studying in Class 6 with excellent academic performance.

Family history

• Non-consanguineous parentage.
• Father 42 years, teacher, healthy; Mother 38 years, homemaker, healthy.
• Younger brother (6 years old) is attending school, healthy.
• No family history of lymphoma, leukemia, or autoimmune connective tissue disorders.

Immunization history

• Fully immunized per the National Immunization Schedule, including BCG scar present over left deltoid.

Dietary history

• Vegetarian diet; intake reduced by 30% over the past month due to systemic malaise.

Food Item	Quantity	Calories (kcal)	Protein (g)
Cow's Milk (toned)	300 mL	180	9.6
Roti (whole wheat, 2)	60 g flour	204	7.0
Boiled Rice	150 g cooked	195	3.9
Toor / Chana Dal	40 g raw	136	8.8
Seasonal Mixed Sabzi	1 bowl	120	2.4
Paneer Bhurji	40 g	110	7.2
Apple	1 medium (100 g)	60	0.4
Biscuits	30 g	120	2.1
Total Observed Daily Intake	—	1125 kcal	41.4 g

24-Hour Recall Deficit Analysis

$$ \text{Ideal Body Weight (IBW for 11 years, 50th centile WHO)} = 37.0\text{ kg} $$

Nutrient	Expected Intake (ICMR-NIN 2024 for IBW 37.0 kg)	Observed Intake	Deficit	Percentage Deficit
Energy (kcal)	$37.0\text{ kg} \times 52\text{ kcal/kg} = 1924\text{ kcal}$	1125 kcal	799 kcal	41.5% Deficit
Protein (g)	$37.0\text{ kg} \times 0.95\text{ g/kg} = 35.15\text{ g}$	41.4 g	Nil (Adequate)	0% Deficit

The expected calories and proteins should be calculated from the ideal body weight, not from current weight.

Socioeconomic and KAP

• Modified BG Prasad Socioeconomic Class II (Upper Middle Class).
• Urban pucca house with municipal treated water and sanitation.

Summary of History

Miss Diya, an 11-year-old female child, presents with an 8-week history of painless, progressive right supraclavicular and cervical lymphadenopathy, cyclical Pel-Ebstein fevers, drenching night sweats, $>10\%$ weight loss, and dry brassy cough when supine, without TB contact or peripheral cytopenic bleeding.

I would like to consider a provisional diagnosis of Lymphoma (most consistent with Hodgkin Lymphoma, Cotswolds Stage II-B), with suspected mediastinal lymph node involvement.

General head to toe examination

• General Appearance: Alert, adolescent girl, mild pallor, visible fullness in the right lower neck.
• Vitals:
  • Heart Rate: 96 beats/minute, regular.
  • Respiratory Rate: 20 breaths/minute, regular.
  • Blood Pressure: $106/68\text{ mmHg}$ ($50^{\text{th}}$ centile, normotensive).
  • Temperature: $37.1^\circ\text{C}$ ($98.8^\circ\text{F}$) axillary (afebrile interval).
  • Capillary Refill Time: $<2$ seconds.
• Anthropometry:

Parameter	Observed	Expected (50th WHO)	Z-score / Centile	Inference
Weight	30.0 kg	37.0 kg	$-1.5\text{ SD}$	Significant weight loss (4 kg / 11.7%)
Pre-morbid Weight	34.0 kg	37.0 kg	$-0.5\text{ SD}$	Baseline normal weight
Height	144.0 cm	144.5 cm	$50^{\text{th}}\text{ centile}$	Normal Stature
Weight-for-Height	30.0 kg for 144 cm	36.0 kg	$-1.8\text{ SD}$	Mild-to-moderate thinness
BMI	$14.5\text{ kg/m}^2$	$17.2\text{ kg/m}^2$	$-1.8\text{ SD}$	Mild-to-moderate thinness

• Lymph Node Examination:
  • Right Anterior Cervical & Supraclavicular Chain:
    • A cluster of enlarged lymph nodes situated along the lower third of the sternocleidomastoid muscle and right supraclavicular fossa.
    • Largest mass measures $4.0\text{ cm} \times 3.0\text{ cm}$; firm-to-rubbery consistency, smooth surface, discrete, non-matted, freely mobile over underlying muscle, and completely non-tender.
    • Overlying skin is normal, mobile, no erythema, warmth, ulceration, or discharging sinus.
  • Other Lymph Node Basins:
    • Left cervical, bilateral axillary, epitrochlear, and inguinal lymph node regions are completely free of palpable enlargement.
• Signs of Superior Mediastinal Syndrome (SMS):
  • No facial plethora, periorbital edema, or chemosis.
  • No engorgement of superficial veins over the neck or anterior chest wall.
  • No inspiratory stridor or hoarseness; cough elicited on lying flat.
• Systemic Signs:
  • Pallor: Mild conjunctival pallor.
  • Icterus, Cyanosis, Clubbing, Edema: Absent.
  • Skin: Normal, no excoriation marks (no active pruritus).

Systemic Examination

Respiratory System & Mediastinum

• Trachea is midline, no tracheal tug.
• Retrosternal Dullness: Percussion over the upper half of the manubrium sterni elicits retrosternal dullness extending 2 cm to the right of the sternal border $\to$ Suggests Anterior Mediastinal Mass.
• Breath sounds: Normal vesicular breath sounds bilaterally; no wheezing, rhonchi, or crepitations.

Abdomen

• Flat, soft, non-tender.
• Liver & Spleen: Neither liver nor spleen is palpable below the costal margins; liver span 10 cm, no splenic dullness.
• No abdominal masses or ascites.

Cardiovascular & Neurological Systems

• Normal heart sounds; no murmurs or pericardial rub. Nervous system examination normal; GCS 15/15.

Summary

Miss Diya, an 11-year-old female child, presents with an 8-week history of painless, firm, rubbery, discrete right cervical and supraclavicular lymphadenopathy ($4 \times 3\text{ cm}$), retromansternal percussion dullness, dry cough when supine, and prominent constitutional B-symptoms (cyclical fever, drenching night sweats, $11.7\%$ weight loss), in the absence of hepatosplenomegaly or peripheral cytopenias.

Final Clinical Diagnosis: Hodgkin Lymphoma (likely Nodular Sclerosis subtype), Cotswolds / Ann Arbor Stage II-B (Two lymph node regions involved on the same side of the diaphragm: right cervical/supraclavicular and mediastinal, with B-symptoms), without evidence of Superior Vena Cava syndrome.

Differential Diagnosis

Disorder	Points IN FAVOR	Points AGAINST
Hodgkin Lymphoma (HL)	Adolescent age; rubbery, painless, discrete supraclavicular nodes; classic B-symptoms; mediastinal widening	Primary Diagnosis
Tuberculous Lymphadenitis	Endemic India; prolonged fever, weight loss, cervical adenopathy	TB nodes are typically matted, periadenitic, adherent, caseating, with cold abscess/sinuses; lacks Pel-Ebstein fever or supraclavicular rubbery nodes
Non-Hodgkin Lymphoma (NHL)	Rapidly enlarging lymph nodes, mediastinal mass	Pediatric NHL has a fulminant doubling time (days to weeks), diffuse extranodal spread, and rapidly precipitates airway collapse; HL has slower course (months)
Reactive Lymphadenopathy	Cervical node enlargement	Reactive nodes are small ($<1.5\text{ cm}$), tender, soft, associated with acute upper respiratory infection, and resolve in 2-4 weeks
Infectious Mononucleosis	Fever, cervical lymphadenopathy	Associated with acute exudative tonsillitis, splenomegaly, and atypical lymphocytes; does not persist for 8 weeks with 11% weight loss

Investigation Protocol & Diagnostic Workup

flowchart TD
    A["Adolescent with Rubbery Supraclavicular Adenopathy & B-Symptoms"] --> B["Erect Chest Radiograph: Assess Mediastinal Mass Ratio (MMR)"]
    B --> C["EXCISIONAL Lymph Node Biopsy of Cervical Node (NOT FNAC!)"]
    C --> D["Histopathology & IHC: Identify Reed-Sternberg Cells (CD15+, CD30+, Pax-5+)"]
    D --> E["Whole-Body 18F-FDG PET-CT: Precise Metabolic Staging (Ann Arbor I to IV)"]
    E --> F["Laboratory Workup: CBC, ESR, Albumin, Ferritin, LDH, Renal/Hepatic Panels"]
    F --> G["Determine Stage: Stage II-B with Mediastinal Involvement"]
    G --> H["Initiate Risk-Adapted Chemotherapy: OEPA / ABVD Regimen"]

1. The Definitive Diagnostic Procedure (VIVA TRAP)

• EXCISIONAL Lymph Node Biopsy (MANDATORY RULE):
  • Fine Needle Aspiration Cytology (FNAC) is STRONGLY CONTRAINDICATED / INSUFFICIENT to diagnose or subtype lymphoma because it aspirates only single cells, destroying the nodal architectural context and almost always missing the rare, scattered Reed-Sternberg cells (which comprise $<1-2\%$ of the tumor mass)!
  • Excision of the entire intact right supraclavicular lymph node under local anesthesia is performed.
• Histopathology & Immunohistochemistry (IHC):
  • Demonstrates collagen bands dividing the lymphoid tissue into circumscribed nodules (Nodular Sclerosis subtype).
  • Background rich in polyclonal lymphocytes, histiocytes, plasma cells, and eosinophils.
  • Identification of classical Reed-Sternberg (RS) cells: large binucleated giant cells with prominent inclusion-like eosinophilic nucleoli ('owl-eye' appearance) and lacunar cell variants.
  • IHC Profile: Tumor cells are strongly positive for CD30 ($100\%$), CD15 ($90\%$), and weakly positive for Pax-5; negative for CD45 (LCA) and CD20.

2. Staging Modalities (18F-FDG PET-CT)

• Whole-Body 18F-Fluorodeoxyglucose (FDG) PET-CT:
  • Intense FDG avidity in right lower cervical and supraclavicular lymph nodes (SUVmax 11.2).
  • Intense FDG avidity in an Anterior Mediastinal Nodal Mass measuring $5.2 \times 4.1\text{ cm}$ (SUVmax 13.8).
  • Mediastinal-to-Thoracic Ratio (MMR): $0.28$ ($<0.33$, confirms non-bulky mediastinal disease).
  • Subdiaphragmatic nodes (para-aortic, mesenteric, iliac) show normal baseline metabolic activity.
  • Liver and spleen are metabolically normal without focal lesions.
  • Skeletal system shows no FDG-avid bone lesions.
• Bone Marrow Trephine Biopsy: Bilateral posterior iliac crest marrow biopsies show normocellular marrow negative for lymphoma infiltration.

3. Laboratory Biomarkers & Stage Grouping

• Erythrocyte Sedimentation Rate (ESR): $78\text{ mm/hr}$ (Markedly elevated; adverse prognostic marker if $>50\text{ mm/hr}$).
• Complete Blood Count: Hb $10.2\text{ g/dL}$ (mild anemia of chronic disease), TLC $11,200/\mu\text{L}$ with $8\%$ eosinophils, Platelets $410,000/\mu\text{L}$.
• Serum Albumin: $3.8\text{ g/dL}$; Serum LDH: $480\text{ U/L}$ (moderately elevated).
• Renal and Hepatic panels completely normal.
• Staging Formulation: Ann Arbor / Cotswolds Stage II-B (Two lymph node regions on the same side of diaphragm with B-symptoms).

Risk-Adapted Multimodal Management Plan

1. Chemotherapy Protocol: Pediatric Oncology Group (OEPA / COPDAC Regimen)

Modern pediatric Hodgkin lymphoma regimens minimize cumulative anthracycline and bleomycin doses to prevent long-term cardiotoxicity and pulmonary fibrosis, and eliminate alkylating agents (procarbazine) to preserve male and female fertility:

• Intermediate-Risk Protocol (Stage II-B):
  • Induction: 2 Cycles of OEPA:
    • O (Vincristine / Oncovin): $1.5\text{ mg/m}^2$ IV on Days 1, 8, 15.
    • E (Etoposide): $100\text{ mg/m}^2$ IV on Days 1 to 5.
    • P (Prednisone): $60\text{ mg/m}^2/\text{day}$ orally on Days 1 to 15.
    • A (Doxorubicin / Adriamycin): $40\text{ mg/m}^2$ IV on Days 1 and 15.
• Interim PET-CT (After 2 Cycles of OEPA):
  • If Adequate Response (Deauville Score 1 or 2): Administer 2 Cycles of COPDAC (Cyclophosphamide, Vincristine, Prednisone, Dacarbazine) and OMIT RADIOTHERAPY COMPLETELY!
  • If Inadequate Response: Administer involved-field radiotherapy (IFRT) at reduced doses ($15-20\text{ Gy}$).

2. Long-Term Survivorship & Toxicity Monitoring

• Cardiac Surveillance: Baseline and annual echocardiogram (Ejection Fraction / Strain imaging) to monitor for anthracycline-induced cardiomyopathy.
• Thyroid Surveillance: Annual TSH monitoring if mediastinal/cervical radiation is utilized.
• Secondary Malignancy Screening: Breast cancer screening via MRI/mammography starting at age 25 or 8 years post-therapy for females receiving thoracic irradiation.
• Overall Prognosis: $>90-95\%$ 5-year event-free survival with modern response-adapted protocols.