Sandbox: differentialdx maria

Genetic lesions and potential therapeutic drugs Adapted from Chiaretti et al
Genes involved	Therapeutic compound
TAL1	HDAC inhibitors
Notch1	Y-secretase inhibitors
ABL1	ABL1 kinase inhibitors
JAK2	JAK2 inhibitors
JAK1	Tyrosine kinase inhibitors

WHO histological classification Tumors of the appendix Adapted from WHO/IARC
Epithelial tumors
Adenoma Tubular Villous Tubulovillous Serrated Carcinoma Adenocarcinoma Mucinous adenocarcinoma Signet-ring cell carcinoma Small cell carcinoma Undifferentiated carcinoma Carcinoid (well differentiated endocrine neoplasm) Tubular carcinoid Goblet cell carcinoid (mucinous carcinoid) Mixed carcinoid-adenocarcinoma Others
Non-epithelial tumors
Neuroma Lipoma Leiomyoma Gastrointestinal stromal tumor Leiomyosarcoma Kaposi sarcoma Others
Secondary tumors
Metastasis (eg. Primary of urogenital tract, breast, lung)
Hyperplastic polyp

CIN is classified in grades:

Histology Grade	Description	Image
–	Normal cervical epithelium
CIN 1 (Grade I)	The least risky type, represents only mild dysplasia, or abnormal cell growth.It is confined to the basal 1/3 of the epithelium. This corresponds to infection with HPV, and typically will be cleared by immune response in a year or so, though can take several years to clear.
CIN 2/3	Formerly subdivided into CIN2 and CIN3.
CIN 2 (Grade II)	Moderate dysplasia confined to the basal 2/3 of the epithelium
CIN 3 (Grade III)	Severe dysplasia that spans more than 2/3 of the epithelium, and may involve the full thickness. This lesion may sometimes also be referred to as cervical carcinoma in situ.

Ultrasound findings of common liver masses
Common liver masses	Ultrasound finding
Hepatic hemangioma	Well-demarcated Homogeneous Hyperechoic mass May be hypoechoic in patients with fatty infiltration
Focal nodular hyperplasia	Detectable lesions Central scar with displacement of peripheral vasculature (Doppler examination)
Hepatic adenoma	Large Right lobe of the liver Central hypoechoic region
Idiopathic noncirrhotic portal hypertension	Isoechoic lesions
Hepatocellular carcinoma	Poorly-defined margins Coarse, irregular internal echoes
Cholangiocarcinoma	Hypo-, iso-, or hyperechoic Homogenous or heterogenous
Metastases	Metastases from adenocarcinoma Multiple and hypoechoic in comparison with the surrounding liver parenchyma

Classification of liver mass
Benign	Malignant
Hepatic hemangioma Focal nodular hyperplasia Hepatic adenoma Idiopathic noncirrhotic portal hypertension Nodular regenerative hyperplasia Regenerative nodules	Hepatocellular carcinoma Cholangiocarcinoma Metastatic disease

Cavitating causes	Conditions	Description
Malignancy	Cancer Primary bronchogenic carcinoma(especially squamous cell carcinoma) Cavitating pulmonary metastases (especially squamous cell carcinoma, GI adenocarincoma, sarcoma)	Cancer Thick wall Irregular shape Disort of adjacent structures
Infection	Pulmonary bacterial abscess/cavitating pneumonia Empyema Post-pneumonic pneumatocoele Septic pulmonary emboli Pulmonary coccidioidomycosis Pulmonary actinomycosis / thoracic actinomycosis Pulmonary nocardiosis Melioidosis Pulmonary cryptococcosis	Abscess: Round in all projections Abruptly interrupts bronchovascular structures May form a acute angle with the costal surface / chest wall Abscesses have thick irregular walls Abscesses usually have an acute angle (claw sign) Empyema: Smoother margins Lentiform shape Distort and compresses adjacent lung Empyemas have obtuse angles
Non-infectious	Granulomatosis with polyangitis Rheumatoid nodules	May be single or multiple Size ranges from 0.5-7 cm 3,5
Vascular	Pulmonary infarct	Consolidation with internal air lucencies, "Bubbly consolidation"; this represent non-infarcted aerated lung parenchyma
Trauma	Pneumatocoeles	Smooth inner margins Contain little if any fluid Wall (if visible) is thin and regular Persist despite absence of symtpoms
Congenital	Congenital cystic adenomatoid malformation (CCAM) Pulmonary sequestration Bronchogenic cyst	Radiological features vary according to disease To learn more about congenital lung cavitations, click in the blue links.

Imaging features of lung mass
Hyperdense pulmonary mass	Cavitating pulmonary mass
Granuloma (most common) Pulmonary hamartoma Bronchogenic carcinoma Carcinoid tumours Pulmonary metastases: Mucoid calcification of mucinous adenocarcinoma Breast carcinoma Gastrointestinal tract adenocarcinoma Dystrophic calcification: Papillary thyroid carcinoma Giant cell tumor of bone Synovial sarcoma Treated pulmonary metastases Osteosarcoma Chondrosarcoma	Cancer Bronchogenic carcinoma (most common) Squamous cell carcinoma Autoimmune Granulomas (Wegener's granulomatosis) Rheumatoid arthritis Rheumatoid nodules Vascular Septic pulmonary embolus Infections (bacterial/fungal) Pulmonary abscess Pulmonary tuberculosis Trauma Pneumatocoeles Youth CPAM Pulmonary sequestration Bronchogenic cyst

Classification of Benign and Malignant Pulmonary Mass
Lung mass (location)	Benign	Malignant
Endobronchial	Bronchial atresia Bronchial hamartoma Bronchogenic cysts Pulmonary bacterial abscess Bronchial anthracofibrosis Allergic bronchopulmonary aspergillosis	Squamous dysplasia of lung Squamous cell lung carcinoma
Parenchymal	Granuloma Pulmonary hamartoma Pulmonary bacterial abscess Pulmonary infract septic Pulmonary emboli	Bronchogenic carcinoma Carcinoid tumors Pulmonary metastases Papillary thyroid carcinoma Giant cell tumor of bones Synovial sarcoma
Pleural	Pleural effusion Empyema Hemothorax Lipoma Splenosis Tuberculosis	Mesothelioma Metastasic pleural disease Invasive thymoma Pleural fibrosarcoma Pleural liposarcoma Primary pleural lymphoma Pleural synovial sarcoma

Radiologic Features Suggestive of Benign or Malignant Solitary Pulmonary Nodules Adapted from American Academy of Family Physicians
Radiologic feature	Benign	Malignant
Size	< 5 mm	> 10 mm
Border	Smooth	Irregular or spiculated
Density	Dense, solid	Nonsolid, “ground glass”
Calcification	Typically a benign feature, especially in “concentric,” “central,” “popcorn-like,” or “homogeneous” patterns	Typically noncalcified, or “eccentric” calcification
Doubling time	Less than one month; more than one year	One month to one year

Recommendations for Follow-up and Management of Nodules <8 mm Detected Incidentally at Non-screening CT

Nodule Size (mm)	Low risk patients	High risk patients
Less than or equal to 4	|No follow-up needed.	Follow-up at 12 months. If no change, no further imaging needed.
>4 - 6	Follow-up at 12 months. If no change, no further imaging needed.	Initial follow-up CT at 6 -12 months and then at 18 - 24 months if no change.
>6 - 8	Initial follow-up CT at 6 -12 months and then at 18 - 24 months if no change.	Initial follow-up CT at 3 - 6 months and then at 9 -12 and 24 months if no change.
> 8	Follow-up CTs at around 3, 9, and 24 months. Dynamic contrast enhanced CT, PET, and/or biopsy	Same at for low risk patients

Note: Newly detected indeterminate nodule in persons 35 years of age or older.

• Low risk patients: Minimal or absent history of smoking and of other known risk factors.
• High risk patients: History of smoking or of other known risk factors.

Differential Diagnosis for Solitary Pulmonary Adapted from Erasmus et al.
Differential Diagnosis	Causes
Malignant neoplasms	Bronchogenic carcinoma Carcinoid tumor Pulmonary lymphoma Pulmonary sarcoma Solitary metastases
Benign neoplasms	Hamartoma Adenoma Lipoma
Infectious inflammatory	Granuloma (tuberculous/fungal) Nocardia infection Round pneumonia Abscess
Non-infectious inflammatory	Rheumatoid arthritis Wegener's granulomatosis Sarcoidosis
Vascular	Arteriovenous malformation Infarction Hematoma
Congenital	Bronchial atresia
Miscellaneous	External object Pseudotumor Pleural thickening

Differential Diagnosis	Similar Features	Differentiating Features
Pulmonary tuberculosis	Cough, weight loss, fatigue, and dyspnea	In pulmonary tuberculosis, differentiating features include: size increase despite optimal medical therapy, patients age is usually younger, hemoptysis is an early feature, and CXR anatomical predilection for upper lobes
Lung abscess	Non-productive cough, weight loss, and chest pain	In lung abscess, differentiating features include: acute or sub-acute onset, CXR anatomical predilection for upper lobes, and usually resolve with antibiotic
Pneumonia	Cough, weight loss, fatigue, and dyspnea	In pneumonia, differentiating features include: good response to antibiotics, acute onset, predilection on CXR is consolidation, laboratory markers indicate infection
Pulmonary fungal infection	Non-productive cough, weight loss, fatigue, and dyspnea	In pulmonary fungal infection, differentiating features include: CXR findings: air-cresecent sign, no response to antibioitcs, and mimics tuberculosis
Other non-small cell lung cancers (adenocarcinoma and squamous cell lung cancer)	Non-productive cough, weight loss, fatigue, and dyspnea	In other non-small cell lung cancers , differentiating features include: histopathologica features, such as larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of "salt-and-pepper" chromatin

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
Sarcoidosis	Chronic cough, weight loss, and dyspnea	In lung abscess, differentiating features include: acute or subacute onset, CXR anatomical predilection for upper lobes, and usually resolve with antibiotic
Pneumonia	Cough, fatigue, and dyspnea	In pneumonia, differentiating features include: good response to antibiotics, acute onset, predilection on CXR is consolidation, laboratory markers indicate infection
Pulmonary fungal infection	Chronic cough, weight loss, hemoptysis, and dyspnea	In primary fungal infection, differentiating features include: CXR findings: air-cresecent sign, no response to antibioitcs, and mimcs tuberculosis
Metastases	Chronic cough, weight loss, hemoptysis, and dyspnea	In metastases, differentiating features include: multicentricity, involvement of the contralateral hemitorax, and usually primary cancer is known

Stage (TNM criteria)	Standard Treatment Options
Occult	Surgery
Stage 0	Surgery Endobronchial therapies
Stages IA and IB	Surgery Radiation therapy IB, if the tumor is >4cm, surgery and chemotherapy
Stages IIA and IIB	Surgery Neoadjuvant chemotherapy Adjuvant chemotherapy Radiation therapy
Stage IIIA	Resected or resectable disease Surgery Neoadjuvant therapy Adjuvant therapy Unresectable disease Radiation therapy Chemoradiation therapy Superior sulcus tumors Radiation therapy alone Radiation therapy and surgery Concurrent chemotherapy with radiation therapy and surgery Surgery alone (for selected patients) Tumors that invade the chest wall Surgery Surgery and radiation therapy Radiation therapy alone Chemotherapy combined with radiation therapy and/or surgery
Stage IIIB	Sequential or concurrent chemotherapy and radiation therapy Chemotherapy followed by surgery (for selected patients) Radiation therapy alone
Stage IV	Cytotoxic combination chemotherapy (first line) Combination chemotherapy with bevacizumab or cetuximab EGFR tyrosine kinase inhibitors (first line) EML4-ALK inhibitors in patients with EML-ALK translocations Immune checkpoint inhibition with nivolumab for selected patients with squamous or nonsquamous metastatic Maintenance therapy following first-line chemotherapy Endobronchial laser therapy and/or brachytherapy (for obstructing lesions) External-beam radiation therapy (primarily for palliation of local symptomatic tumor growth)
Recurrent	Radiation therapy (for palliation) Chemotherapy or kinase inhibitors alone EGFR inhibitors in patients with/without EGFR mutations EML4-ALK inhibitors in patients with EML-ALK translocations Surgical resection of isolated cerebral metastasis (for highly selected patients) Laser therapy or interstitial radiation therapy (for endobronchial lesions) Stereotactic radiation surgery (for highly selected patients)

Type of tumor	Biopsy findings
Lung adenocarcinoma	Nuclear atypia Eccentrically placed nuclei Abundant cytoplasm - classically with mucin vacuoles Often conspicuous nucleoli Nuclear pseudoinclusions
Squamous cell lung carcinoma	Central nucleus Dense appearing cytoplasm, usu. eosinophilic Small nucleolus Intracellular bridges - classic
Large cell lung carcinoma	Large polygonal cells and anaplastic cells Solid nests without obvious squamous or glandular differentiation Moderately abundant cytoplasm Well defined cell borders Vesicular nuclei, prominent nucleoli
Adenosquamous carcinoma	Substantial amounts of squamous and glandular differentiation Positive stains for TTF1 and p63 in squamous component
Sarcomatoid carcinoma	Sarcoma-like differentiation Spindle cells vary morphologically from epithelioid to strikingly spindled and are arranged in haphazard fascicles or storiform pattern Moderate to abundant, dense, eosinophilic cytoplasm
Carcinoid tumor	Medium sized polygonal cells with lightly eosinophilic cytoplasm Low nuclear grade, round to oval finely granular nuclei; may have rosettes or small acinar structures with variable mucin Scanty vascular stroma, occasionally amyloid stroma with bone
Salivary gland tumor	Organized in round and sometimes confluent islands, rich in matrix and with dispersed condrocyte-type cells

Organization Screening Guidelines for Non Small Cell Lung Cancer Adapted from CDC (2016)
Organization	Groups eligible for screening	Year
American Academy of Family Practice	Evidence is insufficient to recommend for or against screening	2013
American Association of Thoracic Surgery	1. Age 55 to 79 years with 30 pack year smoking history. 2. Long term lung cancer survivors who have completed 4 years of surveillance without recurrence and who can tolerate lung cancer treatment following screening to detect second primary lung cancer until the age of 79. 3. Age 50 to 79 years with a 20 pack year smoking history and additional comorbidity that produces a cumulative risk of developing lung cancer ≥ 5% in 5 years	2012
American Cancer Society	Age 55 to 74 years with ≥30 pack year smoking history, who either currently smoke or have quit within the past 15 years, and who are in relatively good health.	2015
American College of Chest Physicans	Age 55 to 74 years with ≥30 pack year smoking history,who either currently smoke or have quit within the past 15 years	2013
American Society of Clinical Oncology	Age 55 to 74 years with ≥30 pack year smoking history,who either currently smoke or have quit within the past 15 years	2012
American Lung Association	Age 55 to 74 years with ≥ 30 pack year smoking history and no history of lung cancer	2012
Medicaid Services	Age 55 to 77 years with ≥ 30 pack year smoking history and smoking cessation < 15 years	2015
National Comprehensive Cancer Network	Age 55 to74 years with ≥30 packyear smoking history and smoking cessation < 15 years OR Age ≥ 50 years and ≥20 pack year smoking history and additional risk factor (other than secondhand smoke exposure	2015
U.S Preventive Services Task Force	Age 55 to 80 years with ≥30 pack year smoking history and smoking cessation < 15 years.	2013

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.