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8.4 Head and Neck, Bone & Soft Tissue Cancer and Cancer of Unknown Primary

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ABIM Internal Medicine Exam

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1 Chapter 0: The ABIM Exam, Blueprint & Study Strategy

0.1 Exam Format, Question Types & the 2026 Blueprint 0.2 Eligibility, Registration, Fees & Exam-Day Logistics 0.3 Scoring, the Passing Standard & Score Reports 0.4 Building a Blueprint-Weighted Study Plan

2 Chapter 1: Cardiovascular Disease (14% of Exam)

1.1 Ischemic Heart Disease & Acute Coronary Syndromes 1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI 1.3 Atrial Fibrillation, Atrial Flutter & Stroke Prevention 1.4 Supraventricular Tachycardias, Ventricular Arrhythmias & Bradycardias 1.5 Heart Failure: Classification, Staging & Guideline-Directed Medical Therapy 1.6 Device Therapy, HFpEF & the Cardiomyopathies 1.7 Valvular Heart Disease & Endocarditis Prophylaxis 1.8 Pericardial Disease & Acute Aortic Syndromes 1.9 Hypertension: Classification, Diagnosis & Secondary Causes 1.10 Hypertensive Crises & Dyslipidemia 1.11 Adult Congenital Heart Disease & Coarctation of the Aorta 1.12 Syncope: Reflex, Orthostatic & Cardiac Causes 1.13 Cardiac Physical Examination, Murmurs & Antithrombotic Selection

3 Chapter 2: Endocrinology, Diabetes & Metabolism (9% of Exam)

2.1 Diabetes Mellitus: Diagnosis, Glycemic Targets & Pharmacotherapy 2.2 Insulin Therapy, Hyperglycemic Emergencies & Chronic Complications 2.3 Thyroid Function Testing & Hypothyroidism 2.4 Thyrotoxicosis, Thyroid Storm & Thyroid Nodules 2.5 Adrenal & Pituitary Disorders 2.6 Hypercalcemia, Hypocalcemia & Disorders of Mineral Metabolism 2.7 Osteoporosis & Paget Disease of Bone 2.8 Ovarian, Testicular & Reproductive Endocrine Disorders 2.9 Hypoglycemia, Endocrine Tumors, Polyglandular Syndromes & Severe Hypertriglyceridemia

4 Chapter 3: Gastroenterology & Hepatology (9% of Exam)

3.1 Esophageal Disease 3.2 Stomach & Duodenal Disease and Gastrointestinal Hemorrhage 3.3 Inflammatory Bowel Disease 3.4 Celiac Disease & Irritable Bowel Syndrome 3.5 Diverticular Disease & Colorectal Cancer Screening 3.6 Viral Hepatitis, Steatotic & Alcohol-Associated Liver Disease 3.7 Cirrhosis & the Complications of Portal Hypertension 3.8 Acute Pancreatitis 3.9 Chronic Pancreatitis & Biliary Tract Disease 3.10 Inherited, Autoimmune & Drug-Induced Liver Disease 3.11 Small Intestinal Disease, Ischemia & Gastrointestinal Complications of HIV

5 Chapter 4: Infectious Disease (9% of Exam)

4.1 Lower Respiratory Tract Infections & Sepsis Syndromes 4.2 Viral Respiratory Pathogens & Tuberculosis 4.3 Central Nervous System Infections 4.4 Skin, Soft Tissue, Bone & Joint Infections 4.5 Infective Endocarditis & Cardiovascular Infection 4.6 Clostridioides difficile & Catheter-Related Bloodstream Infection 4.7 HIV Diagnosis, Antiretroviral Therapy & Prevention 4.8 Opportunistic Infections & Sexually Transmitted Infections 4.9 Fever of Unknown Origin, Neutropenic Fever & Toxic Shock 4.10 Travel-Related Illness, Vector-Borne Disease & Outbreaks 4.11 Infection Prevention, Nosocomial Infection & Postexposure Prophylaxis 4.12 Rheumatic Fever, Poststreptococcal Disease, Enteric & Hepatic Infections

6 Chapter 5: Pulmonary Disease (9% of Exam)

5.1 COPD: Diagnosis, GOLD Classification & Initial Pharmacotherapy 5.2 Interventions That Reduce COPD Mortality & Exacerbation Management 5.3 Asthma: Diagnosis, Stepwise Therapy & Status Asthmaticus 5.4 Interstitial Lung Disease & Idiopathic Pulmonary Fibrosis 5.5 Sarcoidosis, Hypersensitivity Pneumonitis & Occupational Lung Disease 5.6 Pulmonary Embolism: Diagnosis, Risk Stratification & Anticoagulation 5.7 Pulmonary Hypertension & Sleep-Disordered Breathing 5.8 Acute Respiratory Distress Syndrome & Mechanical Ventilation 5.9 Pleural Disease, Empyema & Pneumothorax 5.10 Bronchiectasis, Cystic Fibrosis & Restrictive Lung Disease 5.11 Evaluation of Cough, Dyspnea, Hemoptysis & the Solitary Pulmonary Nodule

7 Chapter 6: Rheumatology & Orthopedics (9% of Exam)

6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations 6.2 Antirheumatic Pharmacotherapy & the Spondyloarthropathies 6.3 Gout: Pathophysiology & Acute Management 6.4 Urate-Lowering Therapy & Calcium Pyrophosphate Deposition Disease 6.5 Osteoarthritis 6.6 Systemic Lupus Erythematosus 6.7 Systemic Sclerosis, Sjogren Syndrome & Inflammatory Myopathies 6.8 The Vasculitides 6.9 Regional Musculoskeletal Syndromes, Back Pain & Sports Injuries 6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease 6.11 Osteonecrosis & Metabolic Bone Disease

8 Chapter 7: Hematology (6% of Exam)

7.1 Approach to Anemia & the Microcytic Anemias 7.2 Macrocytic, Normocytic & Hemolytic Anemias 7.3 Hemoglobinopathies, Thalassemias & Paroxysmal Nocturnal Hemoglobinuria 7.4 Platelet Disorders, Thrombocytopenia & the Bleeding Patient 7.5 Coagulation Factor Disorders, Thrombophilia & Anticoagulant Reversal 7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms 7.7 Lymphomas & Plasma Cell Disorders 7.8 Myelodysplastic Syndrome, Myeloproliferative Neoplasms & Porphyria 7.9 Transfusion Medicine & Late Complications of Transplantation

9 Chapter 8: Medical Oncology (6% of Exam)

8.1 Breast, Lung, Colorectal & Prostate Cancer 8.2 Oncologic Emergencies 8.3 Genitourinary & Gynecologic Malignancies 8.4 Head and Neck, Bone & Soft Tissue Cancer and Cancer of Unknown Primary 8.5 Complications of Cancer & Its Treatment 8.6 Cancer Prevention, Survivorship & Psychosocial Care

10 Chapter 9: Nephrology & Urology (6% of Exam)

9.1 Acute Kidney Injury: Staging, Etiology & Urine Microscopy 9.2 Glomerular Disorders & Nephrotic Syndrome 9.3 Nephritic Syndromes, RPGN & Indications for Renal Replacement Therapy 9.4 Chronic Kidney Disease: Staging & Progression Retardation 9.5 Complications of Chronic Kidney Disease: Anemia, CKD-MBD & Acidosis 9.6 Hyponatremia, Hypernatremia & Water Balance 9.7 Potassium Disorders & Systematic Acid-Base Analysis 9.8 Renal Tubular Acidosis & Nephrolithiasis 9.9 Prostate Disorders, Urinary Incontinence & Other Urologic Conditions 9.10 Cystic Kidney Disease, Obstructive Uropathy, Tubulointerstitial Disease & Hematuria

11 Chapter 10: Neurology (4% of Exam)

10.1 Acute Ischemic Stroke: Syndromes & Reperfusion 10.2 Transient Ischemic Attack, Secondary Prevention & Hemorrhagic Stroke 10.3 Headache & Facial Pain 10.4 Seizures, Epilepsy & Movement Disorders 10.5 Multiple Sclerosis & Neuromuscular Junction Disorders 10.6 Motor Neuron Disease & Acute Peripheral Neuropathy 10.7 Cranial Neuropathies & Neuro-Ophthalmology 10.8 Peripheral Neuropathies, CNS Tumors & Other Neurologic Disorders

12 Chapter 11: Psychiatry & Behavioral Health (4% of Exam)

11.1 Major Depressive Disorder & Medical Mimics 11.2 Antidepressant Pharmacotherapy & Treatment-Resistant Depression 11.3 Bipolar Disorder, Mood Stabilizers & Lithium Toxicity 11.4 Anxiety, Stress-Related & Obsessive-Compulsive Disorders 11.5 Alcohol Use Disorder & Withdrawal 11.6 Pharmacotherapy for Alcohol & Opioid Use Disorder 11.7 Toxidromes, Psychiatric Emergencies & Suicide Risk Assessment 11.8 Psychotic, Somatic Symptom, Factitious & Personality Disorders 11.9 Eating Disorders, Sleep Disorders & Sexual Health

13 Chapter 12: Dermatology (3% of Exam)

12.1 Dermatitis, Papulosquamous & Inflammatory Dermatoses 12.2 Acne, Rosacea & Cutaneous Infections 12.3 Herpes Zoster & Autoimmune Blistering Diseases 12.4 Nodules, Tumors & Cutaneous Oncology 12.5 Dermatologic Emergencies & Severe Cutaneous Adverse Reactions 12.6 Pigment Disorders, Alopecia, Nail Disease & Photosensitivity 12.7 Vascular Dermatoses, Environmental Injury & Cutaneous Signs of Systemic Disease

14 Chapter 13: Obstetrics & Gynecology / Women's Health (3% of Exam)

13.1 Contraception, Preconception Care & Teratogenicity 13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes 13.3 Thyroid Disease & Venous Thromboembolism in Pregnancy 13.4 Menopause & Menopausal Hormone Therapy 13.5 Abnormal Uterine Bleeding, Endometrial Disease & Gynecologic Cancer Screening 13.6 Breast Disorders & Diseases of the Vulva and Vagina 13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications

15 Chapter 14: Geriatric Syndromes (3% of Exam)

14.1 Comprehensive Geriatric Assessment & Frailty 14.2 Falls, Gait Assessment & Polypharmacy 14.3 Urinary Incontinence & Pressure Injuries in Older Adults 14.4 Mild Cognitive Impairment, Dementia & Its Subtypes 14.5 Delirium & the Pharmacotherapy of Cognitive Disorders 14.6 Palliative Care, Hospice & Advance Care Planning 14.7 Chronic Wounds, Nutrition, Swallowing, Constipation & Hip Fracture 14.8 Sensory Impairment, Dizziness, Elder Mistreatment & Care Settings

16 Chapter 15: Allergy & Immunology (2% of Exam)

15.1 Anaphylaxis: Recognition & Emergency Management 15.2 Urticaria & Angioedema 15.3 Drug Allergy, Desensitization & Adult Immunodeficiency 15.4 Food Allergy, Insect Venom Hypersensitivity, Serum Sickness & Contrast Reactions 15.5 Rhinitis, Conjunctivitis, Eosinophilic & Mast Cell Disorders

17 Chapter 16: Preventive Medicine, Immunization & Clinical Epidemiology

16.1 The USPSTF Framework & Evidence-Based Cancer Screening 16.2 Cardiovascular & Metabolic Screening and Primary Prevention 16.3 Adult Immunization & Vaccines in Special Populations 16.4 Clinical Epidemiology, Biostatistics & Study Design

18 Chapter 17: Miscellaneous - Ethics, Patient Safety & Quality Improvement (2% of Exam)

17.1 Principles of Bioethics & Decisional Capacity 17.2 Informed Consent, Treatment Refusal & Special Scenarios 17.3 Surrogate Decision-Making, Advance Directives & Confidentiality 17.4 Patient Safety Science, Medical Error & Diagnostic Reasoning 17.5 Quality Improvement Methods, Health Disparities & Health Equity

19 Chapter 18: Perioperative Medicine & Medical Consultation

18.1 Preoperative Cardiovascular Risk Assessment 18.2 Preoperative Pulmonary Risk & Perioperative Medication Management 18.3 Perioperative Anticoagulation, Bridging & Postoperative Complications

20 Chapter 19: Ophthalmology (1% of Exam)

19.1 The Acute Red Eye & Ophthalmic Emergencies 19.2 Painless Vision Loss & Chronic Ophthalmic Disease 19.3 Uveitis, Scleritis & Orbital Disease

21 Chapter 20: Otolaryngology & Dental Medicine (1% of Exam)

20.1 Dizziness, Vertigo & Epistaxis 20.2 Ear Disorders, Hearing Loss & Upper Respiratory Infections 20.3 Oral Cavity, Salivary Gland, Laryngeal & Taste and Smell Disorders

8.4 Head and Neck, Bone & Soft Tissue Cancer and Cancer of Unknown Primary

Key Takeaways Explain This Topic AI

Neoplasms of the head and neck, bone tumors, soft tissue cancer, cancer of unknown primary and oncologic complications of HIV infection are separately enumerated blueprint subsections.

Human papillomavirus-associated oropharyngeal squamous cell carcinoma has a markedly better prognosis than tobacco and alcohol-related disease.

A persistent neck mass in an adult requires fine-needle aspiration rather than excisional biopsy, which can compromise subsequent definitive surgery.

Immunohistochemistry and gene expression profiling identify favorable subsets of cancer of unknown primary that are treated as specific curable malignancies.

Kaposi sarcoma is an AIDS-defining malignancy driven by human herpesvirus 8 whose primary treatment is antiretroviral therapy.

Last updated: August 2026

1. Head and Neck Cancer

The blueprint lists neoplasms of the head and neck , with thyroid nodules and thyroid cancer as one subtopic and other head and neck neoplasms as another. The great majority are squamous cell carcinomas of the oral cavity, oropharynx, larynx or hypopharynx.

Two distinct diseases with the same histology

  • HPV-associated Tobacco/alcohol-associated
  • Site Oropharynx — tonsil, base of tongue Oral cavity, larynx, hypopharynx
  • Typical patient Younger, non-smoker Older, heavy smoker and drinker
  • Marker p16 immunostaining positive p16 negative
  • Presentation Cystic neck node , often with a small primary Local symptoms
  • Prognosis Substantially better Worse

This distinction changes staging and prognosis, and p16 testing is standard on oropharyngeal tumors. HPV vaccination is expected to reduce incidence.

  • Warning symptoms
  • Persistent hoarseness beyond two to three weeks — requires laryngoscopy , particularly in a smoker

Unilateral otalgia with a normal ear examination — referred pain via the glossopharyngeal or vagus nerve from a pharyngeal primary

Persistent oral ulcer or white or red patch — leukoplakia and especially erythroplakia carry malignant potential and require biopsy

  • Dysphagia, odynophagia, unilateral nasal obstruction or epistaxis
  • A neck mass persisting beyond two to three weeks in an adult over 40
  • The neck mass rule

A persistent neck mass in an adult is metastatic squamous cell carcinoma until proven otherwise. Fine-needle aspiration is the correct first diagnostic step. Open excisional biopsy of a neck node should be avoided , because it disrupts tissue planes, seeds the wound and worsens outcomes of subsequent neck dissection and radiation. If aspiration shows squamous carcinoma, the next step is examination under anesthesia with directed biopsies to find the primary.

2. Bone Tumors

A named blueprint subsection. The internist role is recognizing when bone pain requires imaging and distinguishing benign from aggressive lesions.

Red-flag features of bone pain: pain that is worse at night or at rest rather than with activity, progressive over weeks, associated with a palpable mass, or accompanied by systemic symptoms.

Radiographic aggressiveness:

  • Suggests benign Suggests malignant
  • Well-defined sclerotic margin Wide zone of transition, ill-defined margins
  • Intact cortex Cortical destruction, soft-tissue mass
  • No periosteal reaction Aggressive periosteal reaction — sunburst, Codman triangle, onion skin

Primary tumor Typical age Site Radiographic clue

Osteosarcoma Adolescents; second peak in older adults with Paget disease or prior radiation Metaphysis of distal femur, proximal tibia Sunburst periosteal reaction, Codman triangle

Ewing sarcoma Children, young adults Diaphysis, pelvis Onion-skin periosteal reaction; may mimic osteomyelitis with fever and elevated markers

  • Chondrosarcoma Older adults Pelvis, proximal femur Ring-and-arc calcification
  • Giant cell tumor Young adults Epiphysis, around the knee Lytic, eccentric, subarticular

In adults, a bone lesion is far more likely to be a metastasis or myeloma than a primary bone tumor. Metastases to bone come most often from breast, prostate, lung, kidney and thyroid . Prostate metastases are characteristically osteoblastic ; myeloma and renal cell are purely lytic — and myeloma is therefore poorly detected on bone scintigraphy , which requires osteoblastic activity.

A suspected primary bone sarcoma should be biopsied at the center that will perform the definitive resection , because a poorly placed biopsy tract can convert a limb-sparing operation into an amputation.

3. Soft Tissue Cancer

Soft tissue sarcomas are uncommon and are frequently mistaken for lipomas or hematomas, causing delayed diagnosis.

Features of a soft tissue mass that require MRI and referral before any excision:

  • Larger than about 5 cm
  • Deep to the fascia
  • Enlarging
  • Painful
  • Recurrent after prior excision

Do not shell out an undiagnosed deep soft tissue mass. An unplanned excision contaminates tissue planes and compromises limb-sparing surgery — the same principle as bone sarcoma.

Specific entities worth knowing:

Gastrointestinal stromal tumor (GIST) — KIT (CD117)-positive, driven by KIT or PDGFRA mutation, treated with imatinib ; the exemplar of targeted therapy in sarcoma.

Kaposi sarcoma — see below.

Angiosarcoma — arises in chronically lymphedematous limbs (Stewart-Treves syndrome after axillary dissection) and in irradiated fields.

Radiation-associated sarcoma — a late second malignancy appearing years after therapeutic irradiation.

4. Cancer of Unknown Primary

Metastatic malignancy with no identifiable primary site after a standard evaluation. The conceptual error the exam tests is exhaustive searching for the primary ; the correct strategy is identifying the favorable subsets that have specific, effective treatment .

Standard evaluation

History and physical examination including breast, pelvic, rectal and testicular examination; complete blood count and chemistry; CT of chest, abdomen and pelvis; mammography in women; PSA in men; age-appropriate endoscopy directed by symptoms; and biopsy with immunohistochemistry .

Immunohistochemistry is the workhorse:

  • Marker Suggests
  • Cytokeratin 7 positive / 20 negative Lung, breast, ovary, endometrium, pancreatobiliary
  • CK7 negative / CK20 positive Colorectal
  • TTF-1 Lung, thyroid
  • PSA / NKX3.1 Prostate
  • GCDFP-15, GATA3 Breast
  • CDX2 Gastrointestinal
  • S100, SOX10, HMB-45 Melanoma
  • PAX8 Renal, thyroid, gynecologic
  • Leukocyte common antigen (CD45) Lymphoma
  • The favorable subsets — these are the exam answers

Presentation Treat as Why it matters

Isolated axillary adenopathy in a woman , adenocarcinoma Stage II breast cancer Potentially curable; treat even with a normal mammogram and MRI

Peritoneal carcinomatosis in a woman , papillary serous histology Advanced ovarian cancer Cytoreduction plus platinum-based therapy

Midline nodal mass in a young man , poorly differentiated Extragonadal germ cell tumor Curable with platinum-based chemotherapy

  • Cervical nodal squamous cell carcinoma Head and neck primary Treat with definitive locoregional therapy
  • Inguinal nodal squamous cell carcinoma Anogenital primary Locoregional therapy
  • Single metastatic site Site-directed local therapy Long-term control possible
  • Blastic bone metastases with elevated PSA in a man Prostate cancer Highly treatable with androgen deprivation
  • Neuroendocrine histology Neuroendocrine carcinoma Platinum-etoposide, often responsive

Outside these subsets, prognosis is poor and treatment is empiric platinum-based therapy, increasingly guided by molecular profiling and by biomarkers predicting benefit from immune checkpoint inhibition.

PET/CT is most useful in the cervical nodal squamous cell subset, where it identifies an occult head and neck primary in a meaningful proportion of patients.

5. Oncologic Complications of HIV Infection

A separately enumerated blueprint subsection.

AIDS-defining malignancies

Kaposi sarcoma — driven by human herpesvirus 8 . Violaceous cutaneous or mucosal plaques and nodules, sometimes with pulmonary or gastrointestinal involvement. Antiretroviral therapy is the foundation of treatment , and limited disease often regresses with immune reconstitution alone; systemic chemotherapy is added for visceral or extensive disease. Kaposi sarcoma may transiently worsen as an immune reconstitution inflammatory syndrome after antiretroviral initiation.

Aggressive non-Hodgkin lymphoma — diffuse large B-cell and Burkitt lymphoma. Primary central nervous system lymphoma occurs at very low CD4 counts and is Epstein-Barr virus-driven; on imaging it must be distinguished from toxoplasmosis, and cerebrospinal fluid EBV DNA with thallium or PET imaging assists.

Invasive cervical cancer — HPV-driven, requiring intensified screening.

Non-AIDS-defining malignancies

As survival has improved, these now account for most cancer deaths in people with HIV: anal cancer (HPV-driven, markedly elevated incidence), Hodgkin lymphoma , lung cancer (elevated even after adjusting for smoking), hepatocellular carcinoma (with hepatitis B or C coinfection), and head and neck cancer.

The unifying principles: sustained antiretroviral therapy with immune reconstitution reduces the incidence of most HIV-associated malignancies; routine age-appropriate cancer screening must not be omitted in people with HIV; and drug interactions between antiretrovirals and chemotherapy — particularly with ritonavir or cobicistat boosting — require pharmacist review before treatment.