Hodgkin’s Lymphoma: The Hidden Cancer Behind Persistent Cough, Weight Loss, and Mediastinal Masses — A Radiology-Guided Diagnostic Approach

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Hodgkin’s Lymphoma: A Radiologist’s Perspective on Diagnosis, Imaging, and Survival

A Clinical Story That Began With a Persistent Cough

A 41-year-old man arrived at the emergency department with symptoms that had slowly worsened over nine months.

Initially, he experienced a mild cough.

Then came exertional dyspnea.

Soon afterward, he developed night sweats and an unexplained 10-kg weight loss.

Physical examination revealed extensive painless cervical and supraclavicular lymphadenopathy. Chest radiography demonstrated bilateral hilar enlargement, raising immediate concern for a serious thoracic pathology. Subsequent CT imaging revealed extensive mediastinal, hilar, and axillary lymphadenopathy. Excisional lymph node biopsy ultimately confirmed nodular sclerosis Hodgkin’s lymphoma, the most common subtype of classical Hodgkin lymphoma.

This case illustrates why medical imaging, particularly CT scan diagnosis and radiology interpretation, remains indispensable in the evaluation of unexplained mediastinal masses and lymphadenopathy.

What Is Hodgkin’s Lymphoma?

Hodgkin’s lymphoma (HL) is a malignant neoplasm of the lymphatic system characterized by the presence of Reed-Sternberg cells, giant abnormal B lymphocytes that drive a unique inflammatory microenvironment.

First described by Thomas Hodgkin in 1832, Hodgkin lymphoma accounts for approximately 10% of all lymphomas and remains one of the most curable human cancers when diagnosed early.

Epidemiology

Global Incidence

Hodgkin lymphoma affects approximately:

  • 2–3 individuals per 100,000 annually

  • Young adults (15–35 years)

  • Older adults (>55 years)

The disease exhibits a characteristic bimodal age distribution.

Risk Factors

  • Epstein-Barr virus (EBV) infection

  • Family history

  • Immunosuppression

  • HIV infection

  • Autoimmune disorders

Pathophysiology

The Reed-Sternberg Cell

The hallmark of Hodgkin lymphoma is the Reed-Sternberg (RS) cell.

These cells:

  • Originate from germinal-center B lymphocytes

  • Lose normal B-cell function

  • Secrete cytokines

  • Recruit inflammatory cells

The tumor itself often consists of only a small number of malignant cells surrounded by:

  • Lymphocytes

  • Plasma cells

  • Eosinophils

  • Macrophages

This unique biology explains many clinical manifestations.

Major Histologic Types

Classical Hodgkin Lymphoma (95%)

Subtypes include:

  1. Nodular sclerosis

  2. Mixed cellularity

  3. Lymphocyte-rich

  4. Lymphocyte-depleted

Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

A biologically distinct entity with different immunophenotypic characteristics.

Clinical Presentation

Common Symptoms

Patients often present with:

Lymphadenopathy

Typically:

  • Painless

  • Cervical

  • Supraclavicular

  • Mediastinal

Constitutional "B Symptoms"

  • Fever

  • Night sweats

  • Weight loss

The patient in our case exhibited both night sweats and significant weight loss.

Other Symptoms

  • Chronic cough

  • Dyspnea

  • Chest discomfort

  • Fatigue

  • Pruritus

Why This Case Was Unusual: Severe Hypercalcemia

One remarkable feature was profound hypercalcemia:

Serum calcium: 16.2 mg/dL

This required emergency treatment with:

  • Intravenous saline

  • Bisphosphonates

Laboratory testing also demonstrated markedly elevated LDH.

Although uncommon, Hodgkin lymphoma may cause hypercalcemia through dysregulated vitamin D activation by tumor-associated macrophages.

Imaging of Hodgkin’s Lymphoma

Medical imaging plays a pivotal role in:

  • Detection

  • Staging

  • Treatment planning

  • Response assessment

Figure 1. Chest Radiograph Findings

Chest PA radiograph demonstrating bilateral hilar enlargement (arrows), representing extensive hilar lymphadenopathy.

Radiologic Interpretation

The chest X-ray demonstrates:

  • Bilateral hilar masses

  • Symmetric hilar enlargement

  • Mediastinal widening

Such findings strongly suggest:

  • Lymphoma

  • Sarcoidosis

  • Metastatic nodal disease

In this case, bilateral hilar lymphadenopathy represented nodal involvement by Hodgkin lymphoma.

Diagnostic Contribution

Chest radiography served as the first clue leading to advanced cross-sectional imaging.

Figure 2. Contrast-Enhanced CT Findings

Axial contrast-enhanced CT image showing bulky mediastinal and hilar lymphadenopathy (arrows).

Radiologic Interpretation

CT demonstrates:

  • Large confluent mediastinal nodal masses

  • Bilateral hilar adenopathy

  • Compression of adjacent thoracic structures

  • Extensive supradiaphragmatic disease

The patient's CT confirmed:

  • Hilar lymphadenopathy

  • Mediastinal lymphadenopathy

  • Axillary lymphadenopathy

above the diaphragm.

Diagnostic Contribution

CT imaging:

  • Defined disease extent

  • Guided biopsy selection

  • Provided Ann Arbor staging information

This is a classic example of how CT scan diagnosis dramatically improves diagnostic confidence.

Characteristic CT Imaging Features

Thoracic Findings

The chest is involved in over 80% of patients.

Typical CT findings include:

Feature   Frequency
Mediastinal lymphadenopathy   Very common
Hilar lymphadenopathy   Common
Axillary nodes   Common
Large nodal conglomerates   Common
Pleural effusion   Occasional

Mediastinal Distribution

Most commonly affected stations:

  • Paratracheal

  • Prevascular

  • Aortopulmonary window

  • Hilar nodes

Extranodal Disease

Less common than in non-Hodgkin lymphoma.

Possible sites:

  • Lung

  • Liver

  • Spleen

  • Bone marrow

PET/CT: The Modern Standard


Figure 3. Another example of a PET/CT image

Although CT remains the foundation of staging, PET/CT is now considered essential.

PET/CT allows:

  • Metabolic assessment

  • Whole-body staging

  • Treatment response monitoring

The Deauville scoring system is widely used.

ScoreInterpretation
1–3Complete response
4–5Residual active disease

Differential Diagnosis

Several conditions can mimic Hodgkin lymphoma radiologically.

1. Sarcoidosis

Similarities:

  • Bilateral hilar adenopathy

Differences:

  • Usually lacks bulky mediastinal masses

  • Noncaseating granulomas on biopsy

2. Tuberculosis

Findings:

  • Necrotic lymph nodes

  • Pulmonary infiltrates

3. Non-Hodgkin Lymphoma

Compared with HL:

  • More extranodal disease

  • Less predictable nodal spread

4. Metastatic Lung Cancer

Particularly:

  • Small-cell carcinoma

  • Squamous-cell carcinoma

These were included among the differential considerations in the original case discussion.

Diagnostic Workflow

Step 1: Clinical Suspicion

Red-flag symptoms:

✓ Persistent lymphadenopathy

✓ Night sweats

✓ Weight loss

✓ Chronic cough

Step 2: Initial Imaging

Chest X-Ray

Detects:

  • Hilar enlargement

  • Mediastinal widening

Step 3: CT Scan Diagnosis

Defines:

  • Disease distribution

  • Node size

  • Organ involvement

Step 4: PET/CT

Determines:

  • Metabolic activity

  • Staging

Step 5: Histopathology

Gold standard.

Biopsy identifies:

  • Reed-Sternberg cells

  • Histologic subtype

The patient underwent axillary lymph node excisional biopsy confirming nodular sclerosis Hodgkin lymphoma.

Ann Arbor Staging System

StageDescription
ISingle nodal region
II≥2 regions same side diaphragm
IIIBoth sides diaphragm
IVDiffuse extranodal involvement

Additional designation:

  • A = No B symptoms

  • B = Fever, night sweats, weight loss

Treatment

ABVD Chemotherapy

The traditional first-line regimen:

  • Adriamycin (Doxorubicin)

  • Bleomycin

  • Vinblastine

  • Dacarbazine

The patient described in this case demonstrated an excellent response after 8 months of ABVD therapy.

Radiation Therapy

Used for:

  • Early-stage disease

  • Consolidation after chemotherapy

Immunotherapy

Modern agents include:

  • Brentuximab vedotin

  • PD-1 inhibitors

Examples:

  • Nivolumab

  • Pembrolizumab

Stem Cell Transplantation

Reserved for:

  • Relapsed disease

  • Refractory disease

Prognosis

Hodgkin lymphoma is among the most curable cancers.

Five-Year Survival

Stage    Survival
Localized    >90%
Regional    85–90%
Advanced    75–85%

Factors associated with worse outcomes:

  • Advanced stage

  • High LDH

  • Older age

  • Extensive extranodal disease

Key Radiology Pearls

When You See Bilateral Hilar Lymphadenopathy

Always consider:

  1. Hodgkin lymphoma

  2. Sarcoidosis

  3. Tuberculosis

  4. Metastatic disease

When You See Bulky Mediastinal Masses in Young Adults

Think first about:

  • Hodgkin lymphoma

  • Primary mediastinal B-cell lymphoma

  • Germ cell tumors

Key Takeaways

✅ Hodgkin lymphoma is characterized by Reed-Sternberg cells.

✅ CT is the cornerstone of staging and radiology interpretation.

✅ Mediastinal lymphadenopathy is the most common thoracic manifestation.

✅ PET/CT is critical for response assessment.

✅ ABVD chemotherapy achieves excellent cure rates.

✅ Early diagnosis dramatically improves survival.

Quiz

Question 1. A 25-year-old patient presents with painless cervical lymphadenopathy and mediastinal widening on chest radiography. Which diagnosis is most likely?

A. Tuberculosis

B. Hodgkin lymphoma

C. Pulmonary embolism

D. COPD

E. Pneumothorax

Correct Answer: B. Hodgkin lymphoma. Explanation: Young adults with painless lymphadenopathy and mediastinal adenopathy classically suggest Hodgkin lymphoma.

Question 2. Which imaging modality is most important for initial staging?

A. Ultrasound

B. Mammography

C. PET/CT

D. Fluoroscopy

E. Echocardiography

Correct Answer: C. PET/CT. Explanation: PET/CT provides both anatomic and metabolic assessment and is the current standard for staging.

Question 3. Which cell type is pathognomonic for Hodgkin lymphoma?

A. Plasma cell

B. Neutrophil

C. Reed-Sternberg cell

D. Fibroblast

E. Eosinophil

Correct Answer: C. Reed-Sternberg cell. Explanation: The Reed-Sternberg cell is the defining histopathologic feature of Hodgkin lymphoma.

Frequently Asked Questions (FAQ)

Can Hodgkin lymphoma be cured?

Yes. Cure rates exceed 90% in many early-stage patients.

Is CT or MRI better?

CT remains the primary imaging tool for staging and surveillance. MRI has selected roles but is not routinely used.

What are the first symptoms?

Most patients notice:

  • Enlarged lymph nodes

  • Night sweats

  • Fever

  • Weight loss

Is Hodgkin lymphoma hereditary?

Most cases are sporadic, although family history may increase risk.

What does radiology typically show?

Typical findings include:

  • Mediastinal masses

  • Hilar lymphadenopathy

  • Enlarged cervical nodes

  • PET-avid disease

Recommended Reading

  1. A. Engert et al., "Reduced Treatment Intensity in Patients With Early-Stage Hodgkin's Lymphoma," New England Journal of Medicine, vol. 363, no. 7, pp. 640–652, 2010. DOI: https://doi.org/10.1056/NEJMoa1000067

  2. P. Johnson et al., "Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma," New England Journal of Medicine, vol. 374, pp. 2419–2429, 2016. DOI: https://doi.org/10.1056/NEJMoa1510093

  3. S. Barrington and S. Mikhaeel, "When Should FDG PET-CT Be Used in the Modern Management of Lymphoma?" British Journal of Haematology, vol. 164, pp. 315–328, 2014. DOI: https://doi.org/10.1111/bjh.12602

  4. B. Cheson et al., "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma," Journal of Clinical Oncology, vol. 32, pp. 3059–3068, 2014. DOI: https://doi.org/10.1200/JCO.2013.54.8800

  5. A. Eichenauer et al., "Hodgkin Lymphoma: ESMO Clinical Practice Guidelines," Annals of Oncology, vol. 29, Suppl 4, 2018. DOI: https://doi.org/10.1093/annonc/mdy080

  6. S. Ansell, "Hodgkin Lymphoma: Diagnosis and Treatment," Mayo Clinic Proceedings, vol. 90, no. 11, pp. 1574–1583, 2015. DOI: https://doi.org/10.1016/j.mayocp.2015.07.005

  7. A. Evens and J. Hutchings, "Hodgkin Lymphoma," The Lancet, vol. 390, pp. 2790–2802, 2017. DOI: https://doi.org/10.1016/S0140-6736(17)32262-9

  8. K. Kwee and T. Kwee, "Combined FDG-PET/CT for the Detection of Bone Marrow Involvement in Hodgkin Lymphoma," European Radiology, vol. 21, pp. 274–282, 2011. DOI: https://doi.org/10.1007/s00330-010-1919-0

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