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

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

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:

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:

The favorable subsets — these are the exam answers

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.