Sandbox: differentialdx maria

Procedure	Advantages	Disadvantages
Thoracotomy (surgical opening of the chest)	Allows the most thorough inspection and sampling of lymph node stations, may be followed by resection of tumor, if feasible	Most invasive approach, not indicated for staging alone, significant risk of procedure-related morbidity
Left parasternal mediastinotomy (or anterior mediastinotomy)	Permits evaluation of the aortopulmonary window lymph nodes	More invasive; false-negative rate approximately 10%.
Chamberlain procedure	Access to station 5 (aortopulmonary window lymph node)	Limited applications, invasive
Cervical mediastinoscopy	Still considered the gold standard (usual comparitor) by many, excellent for 2RL 4RL	Does not cover all medastinal lymph node stations, particularly subcarinal lymph nodes (station 7), paraesophageal and pulmonary ligament lymph nodes (stations 8 and 9), the aortopulmonary window lymph nodes (station 5), and the anterior mediastinal lymph nodes (station 6); false-negative rate approximately 20%; invasive
Video-assisted thoracoscopy	Good for inferior mediastinum, station 5 and 6 lymph nodes	Invasive, does not cover superior anterior mediastinum
Transthoracic percutaneous fine needle aspiration (FNA) under CT guidance	More widely available than some other methods	Traverses a lot of lung tissue, therefore high pneumothorax risk, some lymph node stations inaccessible
Bronchoscopy with blind transbronchial FNA (Wang needle)	Less invasive than above methods	Relatively low yield, not widely practiced, bleeding risk

Procedure	Advantages style="padding: 5px 5px; background: #F5F5F5;"|
Endobronchial ultrasound (EBUS)	Direct visualization of lymph node stations. Complements EUS: covers lymph node stations 2R and 4R which are difficult to access by EUS Lower false-negative rate than with blind transbronchial FNA and fewer complications	More invasive than EUS, few practitioners, but rapidly growing in popularity
Endoscopic ultrasound (EUS)	Least invasive modality Uses the esophagus to access mediastinal lymph nodes Excellent for staging lymph nodes Useful for station 2L and 4L, L adrenal, celiac lymph node	Cannot reliably access right sided paratracheal lymph node stations 2 R and 4R Accurate discrimination of primary hilar tumors and involved lymph nodes is important

Differential Diagnosis	Similar Features	Differentiating Features
Pulmonary tuberculosis	Chronic cough, weight loss, hemoptysis, nocturnal diaphoresis, dyspnea	In pulmonary tuberculosis, differentiating features include: increase in diameter despite optimal medical therapy, patients age is usually younger, hemoptisis is an early feature, and CXR anatomical predilection for upper lobes
Lung abscess	Chronic cough, weight loss, hemoptysis, and dyspnea	In lung abscess, differentiating features include: acute or subacute onset, CXR anatomical predilection for upper lobes, and usually resolve with antibiotic
Pneumonia	Chronic cough, weight loss, hemoptysis, and dyspnea	In pneumonia, differentiating features include: good response to antibiotics, acute onset, predilection on CXR is consolidation, laboratory markers indicate infection.
Fungal infection	Chronic cough, weight loss, hemoptysis, and dyspnea	In fungal infection, differentiating features include: CXR findings: air-cresecent sign, no response to antibioitcs, and mimcs tuberculosis.
Chronic eosinophilic pneumonia	Chronic cough, weight loss, hemoptysis, and dyspnea	In chronic eosinophilic pneumonia , differentiating features include: followed by a parasite infection or medication exposure, and increased serum IgE levels

Age-adjusted incidence of lung cancer by histological type Adapted from Wikipedia
All types	66.9
Adenocarcinoma	22.1
Squamous-cell carcinoma	14.4

Age-adjusted incidence of lung cancer by histological type Adapted from Wikipedia
Type	Incidence per 100,000 per year
All types	66.9
Adenocarcinoma	22.1
Squamous-cell carcinoma	14.4

Classification: Mucoepidermoid Carcinomas Adapted from Radiopedia
Salivary gland-confined carcinomas	Major salivary glands (50%)	Parotid gland (40%) Submandibular gland (7%) Sublingual gland (3%)
	Minor salivary glands (50%)	Palate (most common) Retromolar area Floor of the mouth Buccal mucosa Lip Tongue
Other organ mucoepidermoid carcinomas	Thyroid Lung

WHO histological classification system Adapted from WHO/IARC (2006)
Main types	Subtypes	Prevalence
Adenocarcinoma	Adenocarcinoma, mixed Acinar adenocarcinoma Papillary adenocarcinoma Bronchioloalveolar carcinoma Nonmucinous Mucinous Mixed nonmucinous and mucinous or indeterminate Solid adenocarcinoma with mucin production Fetal adenocarcinoma Mucinous (“colloid”) carcinoma Mucinous cystadenocarcinoma Signet ring adenocarcinoma Clear cell adenocarcinoma	40% of lung cancers
Squamous cell carcinoma	Papillary Clear cell Small cell Basaloid	25% of lung cancers
Large cell carcinoma	Large cell neuroendocrine carcinoma Basaloid carcinoma Lymphoepithelioma-like carcinoma Clear cell carcinoma Large cell carcinoma with rhabdoid phenotype	10% of lung cancer
Less common types
Adenosquamous carcinoma	No subtypes	Less than 5%
Sarcomatoid carcinoma	Pleomorphic carcinoma Spindle cell carcinoma Giant cell carcinoma Carcinosarcoma Pulmonary blastoma	Less than 5%
Carcinoid tumor	Typical carcinoid Atypical carcinoid	Less than 5%
Salivary gland tumor	Mucoepidermoid carcinoma Adenoid cystic carcinoma Epithelial-myoepithelial carcinoma	Less than 5%

Genes	Presence in non small cell-lung cancers
EGFR	EGFR mutations are present in approximately 10% to 15% of all non-small cell lung cancers
KRAS	Mutations are present in approximately 30% of pulmonary adenocarcinomas Mutations are present in approximately 5% of pulmonary squamous cell carcinomas Associated with carcinomas with mucinous histology
ALK	Mutations are present in approximately 5% of all non-small cell lung cancers
HER2	Mutations are present in approximately 4% of adenocarcinomas
BRAF	Mutations are present in less than 2% of adenocarcinomas
ROS-1	Mutations are present in less than 2% of adenocarcinomas

Classification Adapted from Radiopedia
Salivary gland-confined carcinomas	Major salivary glands (50%)	Parotid gland (40%) Submandibular gland (7%) Sublingual gland (3%)
	Minor salivary glands (50%)	Palate (most common) Retromolar area Floor of the mouth Buccal mucosa Lip Tongue
Other organ mucoepidermoid carcinomas	Thyroid Lung

Mucoepidermoid carcinoma staging Adapted from American Joint Committee on Cancer (AJCC). 1998
Tumor	T1 - 2cm or less w/o extraparenchymal extension
	T2 - >2cm but not greater than 4cm; and w/o extraparenchymal extension
	T3 - >4cm or with extraparenchymal extension
	T4a - invades skin,mandible, ear canal or facial nerve
	T4b - invades skull base, pterygoid plates or encases carotid
Nodes	NX - Cannot be assessed
	N0 - No regional lymph nodes metastasis
	N1 - Single ipsilateral lymph node, <= 3cm in greatest dimension
	N2 N2a - Single ipsilateral lymph node, 3-6 cm in greatest dimension N2b - Multiple ipsilateral lymph nodes, <= 6cm in greatest dimension N2c - Bilateral or contralateral lymph nodes, <= 6cm in greatest dimension
	N3 - Lymph node(s) >6 cm in greatest dimension
Overall stage	I - T1 N0
	II - T2 N0
	III - T3 N0-1, or T1-3 N1
	IVA - T4a N0-2, or T1-4a
	IVB - T4b N0-3, or T1-4b N3
	IVC - M1

Differential Diagnosis	Similar Features	Differentiating Features
Benign mixed tumor	Painless parotid swelling and facial deformity	In benign mixed tumor , differentiating features include: histopathological findings
Warthin tumor	Painless swelling and facial deformity	In warthin tumor differentiating features include: multicentric presentation (20%) and are usually small (1-4 cm), highly associated with smoking
Adenoid cystic carcinoma	Swelling on salivary gland and facial deformity	In adenoid cystic carcinoma, differentiating features include: tendency for perineural extension, distribution, and mainly occur in relation to the airways
Metastasis	Painless swelling and facial deformity	In metastasis, differentiating features include: primary tumor origin, and histopathological findings.

Type of tumor	Age	Location	Histological features	Imaging features	Origin	Bone/Cartilage
Osteoma	40-50 years	Skull bones	Matured lamellar bone	Sclerotic	Benign	Bone
Osteoid osteoma	10-20 years	Short and long bone diaphysis	Osteiod outlined by osteoblasts, incorporated in a fibrous stroma	Sclerotic	Benign	Bone
Osteosarcoma	11-40 years	Long bones metaphysis	Osteoid and bone formed of malignant osteoblasts and fibroblasts	Sclerotic	Malignant	Bone
Chondroma	30-60 years	Small tubular bones of the hands and feet	Maturated hyaline cartilage (enchondroma/ecchondroma), preserving lobulation	Well-defined	Malignant	Cartilage
Chondrosarcoma	30-60 years	Long bones metaphysic, axial skeleton	Immature cartilage, no preserving lobulation, cells arranged in groups of two or four, with atypia and mitosis	Well-defined	Malignant	Cartilage
Ewing sarcoma	5-25 years	Long bones diaphysis	Small, round, undifferentiated cells, no stroma, a lot of capillary arrangement.	Ill-defined	Malignant	Bone
Giant cell tumor	20-40 years	Knee	Multinucleated giant cells, fusiform cells, mononuclear cells.	Well-defined	Malignant	Bone
Metastases	50-90 years	No site predilection	Frequently adenocarcinomas. Metastases can be blastic or lytic depending on the tumor origin	Sclerotic	Malignant	Bone

Stage	Description
I	Inactive or static lesions
II	Actively growing lesions Most osteochondromas occur in this stage.
III	Actively growing lesions that are locally destructive/aggressive Deformity secondary to mass effect Malignant degeneration Low-grade chondrosarcoma

Differential Diagnosis	Similar Features	Differentiating Features
Enchondroma	Usually found in children, enchondromas are asymptomatic These tumors arise from rests of growth plate Located in the metaphyseal region	In enchondroma, differentiating features include: Imaging features, such as endosteal scalloping, well circumscribed masses, and lytic lessions
Chondroblastoma	Benign cartilaginous neoplasm Affects young patients Located on long bones	In chondroblastoma, differentiating features include: They arise in the epiphysis or apophysis of a long bone Classical location is one-third of the tibia
Periosteal chondroma	Benign cartilaginous neoplasm Commonly located on the proximal humerus and distal femur Affects young patients	In periosteal chondroma, differentiating features include: Symptomps are usually present for a long period of time Imaging features include there is no stalk or peduncle as in an osteochondroma
Chondromyxoid fibroma	Benign cartilaginous neoplasm Located in the metaphyseal region of long bones	In chondromyxoid fibroma, differentiating features include: Occur in young adults (second and third decades) Usually located in the tibia

Type of osteochondroma	Features
Solitary osteochondroma	Non-hereditary 85% of osteochondromas No genetic mutations Located in long bones, 85% of osteochondromas Onset is in early adolescence
Multiple osteochondromas (hereditary)	Hereditary Approximately 20% of osteochondromas Related genetic mutations EXT-1 and EXT-2, Early onset of disease (newborn or children)

Genes implicated in HNPCC	Frequency of mutations in HNPCC families	Locus
MSH2	approximately 60%	2p22
MLH1	approximately 30%	3p21
MSH6	7-10%	2p16
PMS2	relatively infrequent	7p22
PMS1	case report	2q31-q33
TGFBR2	case report	3p22
MLH3	disputed	14q24.3

Type of osteoid osteoma	Characteristics
Intracortical	Dense sclerosis around the nidus
Periosteal	Periosteal reaction
Cancellous (medullary)	Produces very little reactive bone
Subarticular	Simulates arthritis as it produces synovial reactions

Differential Diagnosis	Similar Features	Differentiating Features
Osteoblastoma	Benign, male predilection, and also present in long bones	In osteoblastoma, differentiating features include: uncommon tumor, affect the axial skeleton more frequently and lesions are typically larger than 2 cm
Brodie abscess	Present in children, limb pain, and ocassionaly affects long bones	In brodie abscess differentiating features include: fever, subacute onset, and location is usually affects the metaphysis of tubular bones
Osteosarcoma	Affects same group of population (children and adolescents), patients usually present with bone pain, and the location is usually long bones	In osteosarcoma, differentiating features include: malignancy, infiltration to surrounding tissue, and elevation of serum alkaline phosphatase (ALP)
Enostosis	Affects same group of population (children and adolescents), small size, and the location is usually long bones	In enostosis, differentiating features,include: pathognomonic radiological appearance, incidental finding

Differential Diagnosis	Similar Features	Differentiating Features
Fibrous dysplasia	Benign, often an incidental finding, and affects the same group of patients.	In fibrous dysplasia, differentiating features include: More common presentation is on ribs: 28%, no gender predilection, and complete resection is usually not possible.
Osteoblastoma	Benign, incidental, and male predilection.	In osteoblastoma, differentiating features include: normally affect the axial skeleton, lesions are typically larger than 2 cm, and surgical excision is often the treatment of choice.
Adamantinomas	Benign, slow growing, similar clinical onset.	In adamantinomas , differentiating features include: locally aggressive tumor, common in the 3rd to 5th decades of life, location is usually confined to the jaw.
Chronic sinusitis	Affects same group of population (young to middle aged adults), clinical onset is similar.	In chronic sinusitis, differentiating features include: fever, previous history of acute sinusitis, and lack of facial deformation or imaging findings compatible with osteoma.

Differential Diagnosis	Similar Features	Differentiating Features
Cardiac tamponade	Elevated jugular venous pressure, reduced diastolic filling of the right ventricle, and hypotension.	In cardiac tamponade, differentiating features include: muffled heart sounds, pericardial rub, and electrocardiographic changes.
Chronic obstructive pulmonary disease	Elevated jugular venous pulse (JVP), shortness of breath, and tachypnea.	In cardiac tamponade, differentiating features include: history of chronic bronchitis, coarse crackles with inspiration, and spirometry with FEV1/FVC < 70%.
Mediastinitis	Elevated venous pressure, tachypnea and shortness of breath.	In mediastinitis, differentiating features include: fever, positive confirmation of organisms and elevated leukocytes.
Pneumonia	Hypotension, tachypnea,cough, and chest pain.	In pneumonia, differentiating features include: Bronchial breath sounds, leukocytosis with left shift, positive blood culture and altered laboratory findings (procalitonin).
Acute respiratory distress syndrome	Low blood pressure,hypotension, and shortness of breath.	In cardiac acute respiratory distress syndrome, differentiating features include: acute onset, bilateral infiltrates on chest radiograph sparing costophrenic angles and pulmonary wedge pressure < 18 mmHg.
Syphilis	Enlarged lymph nodes, hypotension and dysphagia.	In syphilis, differentiating features include: Positive treponemal tests, history of unprotected sex, and superficial mucosal patches.

Differential Diagnosis	Similar Features	Differentiating Features
Familial adenomatous polyposis (FAP)	Familial inheritance, increased risk of colorectal cancer, extra-colonic tumors.	Autosomal recessive, 100+ polyps and age under 40, centinel tumors are differently located than HNPCC, such as: Osteomas, dental anomalies, congenital hypertrophy of the retinal pigment epithelium (CHRPE)
Juvenile polyposis	Familial inheritance, autosomal dominant, high risk of GI and non GI cancer, also a germline mutation.	Gastrointestinal hamartomatous polyps, on physical exam lip pigmentation is common.
Cowden syndrome	Rare autosomal dominant inherited disorder, increased risk of colorectal cancer, also has gene mutations.	Intestinal hamartomatous polyps, physical exam may show macrocephaly, gene affected PTEN.