Desmoid tumor differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2]

Overview

Desmoid tumor must be differentiated from acute hematoma, lymphoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma, leiomyosarcoma, neurofibroma, benign fibrous tumor and primitive neuroectodermal tumor.

Differentiating Desmoid tumor from other Diseases

• Extra-abdominal fibromatosis/desmoid tumor must be differentiated from:
  • Fibrosarcoma/fibroblastic sarcoma
  • Low-grade fibromyxoid sarcoma
  • Gardner fibroma
• Intra-abdominal fibromatosis must be differentiated from:
  • Gastrointestinal stromal tumor (GIST)
  • Solitary fibrous tumor (SFT)
  • Inflammatory myofibroblastic tumor (IMT)
  • Sclerosing mesenteritis
  • Retroperitoneal fibrosis due to:
    • Idiopathic [Ormond's disease]
    • Secondary to certain drugs
    • Underlying malignancy such as lymphoma
• Furthermore, desmoid tumors must be differentiated from:
  • Acute hematoma
  • Lymphoma
  • Rhabdomyosarcoma
  • Liposarcoma
  • Leiomyosarcoma
  • Neurofibroma
  • Nodular fasciitis
  • Hypertrophic scars
  • Keloids
  • Benign fibrous tumor
  • Primitive neuroectodermal tumor

Disease entity	Etiology (Genetic or others)	Histopathological findings	Immunohistochemical staining	Benign/Malignant	Risk factors	Common site of involvement	Clinical manifestations	Other associated findings
Desmoid tumor	Sporadic desmoids are associated with following mutations: Wnt/beta-catenin signaling pathway Mutations in CTNNB1 (Beta-catenin gene) (85%) APC gene mutations (10-15%) Familial desmoids/Hereditary desmoid disease is associated with: Mutation in second copy of APC gene Pediatric desmoids have following additional mutations involving: AKT1 E17K (31%) BRAF V600E (19%) TP53 R273H (9%)	Histologically, desmoid tumors consist of: Linearly arranged elongated fibroblasts and myofibroblasts Characterized by elongated, tapered cytoplasm; elongated, vesicular, typical-appearing nuclei; and multiple small nucleoli Surrounded and separated from each other by collagen	Positive for: Nuclear beta-catenin (90%) Vimentin Alpha smooth muscle actin Muscle actin Negative for: Desmin Cytokeratins S-100 Positive antibodies for: Smooth muscle actin Desmin KIT	Benign High local aggressive infiltration High local recurrence	Familial adenomatous polyposis (FAP) Gardner syndrome (inherited desmoids) Turcot syndrome Specific location of APC (adenomatous polyposis coli) gene mutation i.e. 3' end of the APC gene, specifically between codons 1445 and 1580 Family history of desmoid tumor Family history of colon cancer/FAP Estrogen therapy Oral contraceptive pills Pregnancy History of antecedent surgical/accidental trauma at the tumor site (30%) History of breast cancer History of repeated irradiation to a certain body part Female gender Sex hormones/androgens	Abdominal wall (intra-abdominal desmoids) Extra-abdominal desmoids may involve: Shoulder girdle Upper arms Upper legs Hip/buttock region Trunk Head Neck Breast (history of breast cancer/breast surgery Intra-abdominal desmoids may involve: Mesentery Retroperitoneum Bowel	Asymptomatic Painless/painful lump in affected area Pain or soreness caused by compressed nerves or muscles Limping or other difficulty using the legs, feet, arms or hands Decreased movement or range of motion Nausea Vomiting Breast mass (in case of breast desmoids) Loss of sleep Anxiety Abdominal mass/pain Constipation Bloating Intestinal rupture Rectal bleeding Compression of kidneys, ureters, mesenteric vessels and vena cava	Desmoids may be associated with following: Other sporadic tumors such as: Dupuytren's contracture Plantar fibrosis Peyronie's disease Carpal tunnel syndrome Infantile fibrosarcoma Fibrous dysplasia Trisomy 8 Trisomy 20
Fibrosarcoma/Fibroblastic sarcoma	Unknown precise cause Genetics may play a role	Tumor cells resemble mature fibroblasts (spindle-shaped), secreting collagen, with rare mitoses Spliting and merging cells arranged in short fascicles giving "fish bone" appearnace Immature blood vessels (lacking endothelial cells) favor the bloodstream metastasizing "Herringbone" pattern of cell arrangement	Strongly positive for: Vimentin Negative for: Desmin Smooth muscle actin HHF-35 Osteocalcin CD-68 LCA s100 HMB-45 CD-31 CD-34 Cytokeratin Epithelial membrane antigen CD-99	Malignant (with metastatic potential)	Familial adenomatous polyposis Li-Fraumeni syndrome Neurofibromatosis type 1 Nevoid basal cell carcinoma syndrome Retinoblastoma Tuberous sclerosis Werner syndrome Giant cell tumor Enchondroma Fibrous dysplasia Bizarre parosteal osteochondromatous proliferation Chronic osteomyelitis Paget's disease Radiation therapy Surgically treated fracture Bone infarction Exposure to certain chemicals, such as thorium dioxide, vinyl chloride, or arsenic Lymphedema, a swelling in the arms and legs	Primary bone malignancy involving end of long bones: Upper end of tibia Lower end of femur	Localized Pain Swelling Loss of range of motion Pain with weight-bearing Night pain Pathologic fracture of affected bone	Moth-eaten appearance on Xray
Low-grade fibromyxoid sarcoma	Translocation: t(7;18;16) or t(7;16) (q34:p11) Fusion gene: FUS/CREB3 L2 (76%-96%) FUS/CREB3 L1 (4%-6%)	Low to moderate cellularity Regular medium sized nuclei Loosely arranged fascicles of bland spindle cells (whorling pattern) Loose myxoid stroma No cellular atypia Hypocellular/myxoid areas in nodules merging with collagenised areas	Positive for: MUC4 (highly specific and sensitive) Vimentin Occasionally positive for: Desmin SMA EMA CD34 Negative for: Keratin Actin S100 Epithelial membrane antigen CD31 CD68 Cytokeratin (AE1/AE3) Leu-7 Neuron-specific enolase	Benign (histological appearance) High metastasizing potential/local aggressive infiltration High local recurrence	_	Majority occurring in subfascial location and rarely involving subcutis or dermis in following sites: Lower extremities Trunk Groin Upper extremities Thorax Buttocks Abdominal wall Maxillofacial region (rarely)	Painless, slow-growing well-circumscribed mass Average size-5cm (ranges from 1-20cm)	_
Solitary fibrous tumor (SFT)	Intra-chromosomal inversion at: Chromosome 12q13 leading to formation of NAB2–STAT6 chimeric fusion gene (highly variable breakpoints) TERT promoter mutations responsible for: High aggressive potential Metastatic potential	Fibroblast-like tumor cells arranged in a “patternless” pattern Collagenous stroma with staghorn, hyalinized blood vessels Increased mitotic activity Hypercellularity Nuclear atypia Pleomorphism Lipomatous, myxoid, or dedifferentiated variants	Positive for: CD34 Vimentin CD99 (013) In few cases, positive for: Focal keratin reactivity Focal desmin reactivity Negative for: CD31 Cytokeratin Glial fibrillary acidic protein Smooth muscle actin S-100 protein Epithelial membrane antigen	Metastasis(10%-20%) Recurrence (10%-20%)	_	Any anatomic site Serosal membranes such as: Pleura (most common site) Dura of the meninges Peritoneum (or peritoneal cavity) Thoracic cavity (mediastinum, lung parenchyma) Intra-abdominal SFTs involve: Retroperitoneal soft tissue (most common) Liver Diaphragm Pelvis visceras (bladder, prostate, seminal vesicle, kidney) Head and neck sites include: sinonasal tract oral cavity orbit buccal mucosa tongue lower lip Extremities Skin (dermis) Bone	Asymptomatic Pulmonary symptoms (cough, shortness of breath, chest pain, hemoptysis, obstructive pneumonitis because of airway obstruction) Intra-abdominal symptoms (pain,weight loss, dysuria, urinary retention, hydronephrosis, nocturia, constipation, incontinence, vomiting) Paresthesias Symptoms due to nerve impingement Meningeal symptoms Hypoglycemia (due to paraneoplastic syndromes) Symptoms due to hypertrophic pulmonary osteoarthropathy include: Clubbing of the fingers Periostitis Synovial effusions	Paraneoplastic syndromes associated with SFTs include: Doege-Potter syndrome (Refractory hypoglycemia due to IGF2, associated with large peritoneal/pleural tumors) Hypertrophic pulmonary osteoarthropathy (HPO)/Pierre-Marie-Bamberger syndrome( in pleuropulmonary SFTs, secretes hyaluronic acid, cytokines)
Gardner fibroma/Gardner-associated fibroma (GAF)	APC gene mutation	Thick haphazardly arranged collagen bundles (greater abundance of collagen) Few interspersed spindle cells of fibroblast type (less cellularity)	Positive for: Nuclear Beta-catenin (highly positive) CD34 Cyclin-D1 C-myc	Benign	Gardner-type familial adenomatous polyposis Germline mutations in APC gene Inherited desmoids Gardner syndrome The presence of nuchal-type fibroma may indicate Gardner Fibroma, when seen in children	Any part of body: Back (most common) Paraspinal region (most common) Chest wall Abdomen Head Neck Arms Legs	Firm rubbery mass (not a well-circumscribed) Size from 1-10 cm Signs and symptoms due to associated FAP or Gardner syndrome	Precursor lesion for desmoid (50% cases) with a more cellular appearance Precursor lesion for colonic adenomas in asymptomatic FAP patients
Gastrointestinal stromal tumor (GIST)	Activating mutation of: C-KIT ( tyrosine kinase growth factor receptor) gene (Exon 9,13 & 17) Platelet-derived growth factor receptor alpha (PDGFRA on chromosome 4q11-12) gene (Exon 18) BRAF kinase (rare) Protein kinase C (rare) Pediatric GISTs (SDH-deficient) have mutations of one of the: SDH (succinate dehydrogenase)gene subunits GIST as a part of Carney triad has following mutation: Hypermethylation of the SDHC promoter causing epigenetic inactivation of the SDHC gene Wild-type GISTs have following three molecular subtypes: DHX mutations (66%) SDHC promoter hypermethylation (22%) SDH competent (12%) which can further be broken into: NF1 mutations BRAF V600E mutations Other rare mutations or fusions No identified abnormality	GIST cells basically arise from interstitial cells of Cajal (ICCs) and appear as follows on histology: Spindle cells (60%-80%): Fascicular or whorled like appearance Multiple compact cells with minimal stroma Eosinophilic, basophilic or amphophilic cytoplasm Epithelioid cells (20%-30%) Clearly defined with an abundant amphophiliccytoplasm Pleomorphic/mixed cells (occasionally, 10%) Both spindle or epitheloid cells	Positive for: CD117 (overexpression of the receptor tyrosine kinase KIT is the most prominent diagnostic test) CD34 DOG-1 PKC-theta (protein kinase C theta)	Malignant potential (esophageal and colonal GIST) Metastasis (to liver, lungs, bones, subcutis, spleen)	Age group of 50-80years Primary familial GIST syndrome Neurofibromatosis type 1 (NF1) Carney-Stratakis syndrome (dyad of GISTs and paragangliomas) Carney triad (GIST, paraganglioma, and pulmonary chondromas) Urticaria pigmentosa	Can involve any part of GIT: Stomach (most common) Duodenum Omentum Mesentery Esophagus Colon Peritoneum	Depending on tumor size and localization in GIT: Pain Nausea Vomiting Bleeding Obstruction Anemia Melena Abdominal distension Abdominal perforation Peritonitis Volvulus Intussusception Surgical complications associated with resection include: Atelectasis Pneumonia Urinary tract infection Abscess formation Small-bowel obstruction Deep venous thrombosis
Inflammatory myofibroblastic tumor (IMT)	Unknown underlying etiology, may be due to inflammatory reaction to: Infection Underlying low grade malignancy Mutations such as: ALK (anaplastic lymphoma kinase) gene mutations in the tyrosine kinase locus at band 2p23	Spindle cells arranged in short fascicles with a focal storiform (whorled or cartwheel-like) architecture Spindle cells show features of fibroblasts and myofibroblasts Variably dense, chronic, mixed polymorphic infiltrate of mononuclear inflammatory (plasma cells and lymphocytes, histiocytes, and occasional eosinophils) Histiocytes have multinucleated forms with finely vacuolated cytoplasmic lipid droplets Plasma cells with cytoplasmic Russell bodies (globular cytoplasmic inclusions of immunoglobulin) and polyclonal pattern of light chain expression	IL-1 IL-6	Metastatic	Multiorgan disease in association with chronic persistent Eikenella corrodens infection Epstein Barr virus infection Human herpes virus (HHV)-8 infection (Kaposi's sarcoma, multicentric Castleman's disease)	Lungs Bladder Gastrointestinal system Skin Bone CNS	Asymptomatic (70%) Pulmonary IMT presents as: Cough Dyspnea Chest pain Hemoptysis	Also known as: Pseudo-inflammatory tumors Inflammatory pseudotumor Plasma cell granuloma Inflammatory pseudotumor Fibrous histiocytoma Fibroxanthoma Xanthogranuloma
Sclerosing mesenteritis
Retroperitoneal fibrosis	Idiopathic [Ormond's disease] Secondary to certain drugs Underlying malignancy such as lymphoma
Acute hematoma
Lymphoma
Rhabdomyosarcoma
Liposarcoma
Neurofibroma			Positive for: S100
Nodular fasciitis
Hypertrophic scars
Keloids
Benign fibrous tumor
Primitive neuroectodermal tumor