What are the key internal medicine oncology cases that must be known for adult patients with a history of cancer or underlying health conditions?

Essential Internal Medicine Oncology Cases

Internal medicine physicians must be proficient in recognizing and managing cancer of unknown primary (CUP), oncologic emergencies, hereditary cancer syndromes, venous thromboembolism in cancer patients, and treatment-related complications—as these directly impact mortality and quality of life.

Cancer of Unknown Primary (CUP)

Recognition and Prognosis

• CUP carries a median survival of approximately 3 months, with only 20% of patients surviving 1 year 1
• Around half of deaths occur within the first 3 months following diagnosis 1
• Adenocarcinoma and undifferentiated carcinoma have worse outcomes (1-year survival <20%) compared to squamous-cell carcinoma (36% 1-year survival) 1

Critical Diagnostic Workup

• Obtain high-quality tissue specimens for histology and immunohistochemistry (IHC) immediately 1
• Apply morphological pattern-based approach to differentiate epithelial, round, spindle-shaped, and anaplastic cancers 1
• For undifferentiated neoplasms, perform initial IHC screening with:
  • Broad-spectrum keratin (AE1/AE3, OSCAR) for epithelial phenotype 1
  • CD45 for haematolymphoid origin 1
  • SOX10 and/or S100 for melanoma 1

Site-Specific IHC Panels

• For male patients: Rule out metastatic prostate cancer using PSMA and/or NKX3.1 1
• For female patients: Screen with GATA3 for breast cancer and SOX10 for triple-negative breast cancer 1
• For liver adenocarcinoma biopsies: Initial panel should include CK7, CK20, CDX2, and TTF1 (plus GATA3/SOX10 in women) 1
• For colorectal immunophenotype: At least 80% of CRCs show CK7-negative, CK20-positive, CDX2-positive pattern; SATB2 positivity is fairly specific for lower GI origin 1

Favorable CUP Subtypes (20% of cases)

These patients should receive site-specific treatment tailored to the presumed primary, as this improves prognosis 1:

• Single metastatic deposit or oligometastatic disease amenable to local ablative treatment 1
• Women with isolated axillary lymph node metastases (breast-like CUP) 1
• Women with peritoneal carcinomatosis of serous papillary adenocarcinoma (ovary-like CUP) 1
• Squamous-cell carcinoma involving non-supraclavicular cervical lymph nodes (head and neck-like CUP) 1
• Men with blastic bone metastases and/or IHC or serum PSA expression (prostate-like CUP) 1
• Adenocarcinoma with colorectal IHC profile: CK7-negative, CK20-positive, CDX2-positive (colon-like CUP) 1
• Carcinoma with renal-cell histological and immunohistochemical profile (renal-like CUP) 1

Oncologic Emergencies

Tumor Lysis Syndrome (TLS)

• TLS occurs within 12-24 hours after treatment initiation and presents with severe electrolyte abnormalities 2, 3
• Immediate management requires:
  • Vigorous rehydration 3
  • Maintaining urine output 3
  • Lowering uric acid levels 3
• Can lead to kidney failure requiring dialysis and abnormal heart rhythm 2

Hypercalcemia of Malignancy

• Associated with poor outcomes and requires aggressive treatment 3
• Management algorithm:
  • Aggressive rehydration 3
  • Intravenous bisphosphonates 3
  • Subspecialty consultation 3

Febrile Neutropenia

• One of the most common complications of chemotherapy requiring rapid intervention 3
• Management requires:
  • Inpatient therapy 3
  • Rapid administration of empiric antibiotics 3

Structural Emergencies

• Superior vena cava syndrome: Presents with facial edema and collateral venous circulation; treat with intravascular stenting plus chemotherapy/radiation 3
• Malignant epidural spinal cord compression: Managed with steroids and/or surgery plus radiation therapy in conjunction with neurosurgery 3
• Malignant pericardial effusion: Treat with pericardiocentesis or permanent surgical intervention 3

Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

• Suspect in any cancer patient presenting with hyponatremia 3
• Treatment depends on speed of development:
  • Fluid restriction for gradual onset 3
  • Hypertonic saline for rapid development 3

Hereditary Cancer Syndromes

When to Consider Genetic Testing Even Without Family History

The following tumor diagnoses warrant genetic counseling and testing regardless of family history 1:

Common Adult Cancers

• Triple-negative breast cancer (ER/PR/HER2-neu negative), particularly if diagnosed at age ≤60 years: Test BRCA1/BRCA2 1
• Epithelial ovarian, fallopian tube, or primary peritoneal cancer (most commonly high-grade serous histology): Test BRCA1/BRCA2 1
• Colorectal cancer demonstrating mismatch repair deficiency (via MSI analysis and/or IHC, excluding MLH1 promoter hypermethylation and somatic BRAF mutation): Test MLH1/MSH2/MSH6/PMS2/EPCAM 1
• Endometrial cancer demonstrating mismatch repair deficiency: Test MLH1/MSH2/MSH6/PMS2 1

Rare Tumors

• Adrenocortical carcinoma, choroid plexus carcinoma: Test TP53 1
• Pheochromocytoma, paraganglioma: Test VHL, RET, multiple SDH loci 1
• Medullary thyroid cancer: Test RET 1

Essential Family History Elements

Obtain at diagnosis and update periodically 1:

• First-degree relatives: siblings, parents, children 1
• Second-degree relatives: grandparents, aunts, uncles, grandchildren, nieces, nephews, half siblings 1
• Both maternal and paternal sides 1
• Ethnicity (particularly Ashkenazi Jewish ancestry for BRCA mutations) 1
• For each cancer case: age at diagnosis, type of primary cancer, results of any cancer predisposition testing 1

Critical Timing for Reassessment

• End of first phase of therapy 1
• Time of post-treatment summary 1
• Beginning of post-treatment survivorship 1

Venous Thromboembolism (VTE) in Cancer

High-Risk Cancer Types

Patients with the following malignancies have elevated VTE risk 1:

• Very high risk (2 points): stomach, pancreas, primary brain tumor 1
• High risk (1 point): lung, lymphoma, gynecologic, bladder, testicular, renal tumors 1
• Hematologic malignancies also carry elevated risk 1

Risk Assessment Model for Chemotherapy Patients

Use the validated Khorana score to stratify VTE risk in ambulatory patients receiving chemotherapy 1:

• Prechemotherapy platelet count ≥350,000/μL: 1 point 1
• Hemoglobin level <10 g/dL or use of red-cell growth factors: 1 point 1
• Prechemotherapy leukocyte count >11,000/μL: 1 point 1
• Body mass index ≥35 kg/m²: 1 point 1
• High risk: ≥3 points; Intermediate risk: 1-2 points; Low risk: 0 points 1

Treatment-Related VTE Risk

• Thalidomide, lenalidomide, and cisplatin significantly increase VTE risk 1
• Hospitalization or major surgery causes transient risk increase 1

Patient Education Critical Gap

• Fewer than half of cancer patients are aware of their increased VTE risk 1
• Communicate signs and symptoms directly: patients may not report new symptoms assuming they are cancer-related 1
• Provide educational materials and symptom checklists 1

Psychosocial Oncology Emergencies

Physical Manifestations of Anxiety in Cancer Patients

Heightened anxiety is directly associated with increased adverse effects, more physical symptoms, and poorer physical functioning 4, 5:

• Cardiovascular: racing heart, chest pain, palpitations 5, 6
• Respiratory: shortness of breath, feeling of choking 5, 6
• Gastrointestinal: nausea, abdominal distress 5, 6
• Neurological: dizziness, paresthesias, feeling lightheaded 5, 6
• Thermoregulatory: sweating, chills, hot flushes 5, 6

Assessment Algorithm

Before attributing physical symptoms to anxiety, rule out medical causes 5:

• Uncontrolled pain or fatigue 5
• Delirium from infection or electrolyte imbalance 5
• Thyroid disorders 5
• Medication side effects 5
• Substance use or withdrawal 5

Intervention Based on GAD-7 Scores

• Mild symptoms (GAD-7 5-9): Psychoeducation, brief supportive counseling, reinforcement of effective coping strategies 4
• Moderate symptoms (GAD-7 10-14): Referral to stress management programs, CBT or psychodynamic therapy, consider pharmacotherapy 4
• Moderate-severe symptoms (GAD-7 ≥15): Immediate referral to mental health professional, medical leave, evaluate for suicidal ideation 4

Treatment

• First-line: SSRIs (such as sertraline) and cognitive behavioral therapy 5, 6
• Reassess treatment effectiveness using standardized instruments at 4 and 8 weeks 4

Critical Care Considerations

Evolving Outcomes

• Development of more effective oncologic therapies, advances in critical care, and improvements in patient selection have increased survival of critically ill cancer patients 7
• Critical care has become an important cornerstone in the continuum of modern cancer care 7
• Optimal management requires expertise in oncology, critical care, and palliative medicine 7

Common Pitfalls to Avoid

Prognostic Accuracy

• Internal medicine physicians correctly estimate median survival of cancer patients less than 50% of the time and often underestimate survival 8, 9
• Inpatient rotations may provide an unbalanced perspective, as residents primarily care for oncologic patients experiencing significant complications 8
• This can lead patients to make treatment decisions incongruent with their true wishes 8

Educational Gaps

• Prognosis is estimated correctly by only 40% of residents when presented with clinical scenarios 9
• The oncology inpatient rotation alone may not be adequate in educating residents 9
• Focused interventions with interactive cases improve comfort level in estimating prognosis and managing toxicity 9

Rituximab-Specific Warnings

When treating lymphoma or CLL with rituximab, be aware of life-threatening complications 2:

• Fatal infusion-related reactions occur, with approximately 80% during first infusion 2
• Screen all patients for HBV infection before treatment; HBV reactivation can cause fulminant hepatitis, hepatic failure, and death 2
• Progressive multifocal leukoencephalopathy (PML) can occur and may be fatal 2
• Severe mucocutaneous reactions including fatal cases can occur 2
• Premedicate before each infusion and monitor patients closely 2