Disorders of Extracellular Matrix and Soft Tissue Flashcards
How does the skeleton look in someone with Osteogenesis imperfecta? Why?
Often a short stature with many fractures, “brittle bone disease” -> due to fractures thru the growth plate.
Lack of Type 1 collagen causes osteopenia.
What are the other symptoms of osteogenesis imperfecta other than brittle bones? How is it inherited?
ITE
I = eyes, blue sclerae due to relative translucency
T = Teeth, misshapen and discolored due to abnormal dentin
E = ears, impaired hearing
Usually autosomal dominant, but there are some AR forms
What causes Marfan syndrome?
Autosomal dominant disorder of fibrillin-1 gene causing defective sheath around elastin -> chromosome 15
What are the skeletal, ocular, and cardiovascular defects in Marfan syndrome?
Skeletal - tall with long extremities, pectus carinatum or excavatum, hypermobile joints, arachnodactyly
Cardiovascular - Mitral valve prolapse with mitral regurgitation, cystic medial degeneration of aorta -> aortic root dilation with regurgitation and aortic dissections
Ocular - Ectopia lentis, especially upwardly and usually temporally
What are arthrochalasia and dermatosparaxis a feature of?
Arthrochalasia - joint relaxation / joint laxity
Dermatosparaxis - hyperextensible skin
Both are features of Ehlers-Danlos syndrome, caused by collagen defects
What causes hypermobile / classical / vascular type Ehler-Danlos?
Hypermobile - most common type - cause unknown, joint instability only
Classical - defect in type V collagen - joint and skin symptoms
Vascular type - vascular and organ rupture -> due to defective type 3 collagen (Ehlers-Danlos Type IV)
What are superficial fibromatoses and who do they tend to occur in?
Poorly-delineated progressive thickenings within the superficial fascia of palms, soles, or penis composed of dense collagen with bundles of fibroblasts / myofibroblasts
-> lead to skin retraction
What is the most common superficial fibromatosis and what will the clinical symptom commonly be?
Palmar fibromatoses. This thickening can frequently result in finger contraction, especially the 4th and 5th fingers
= “Dupuytren contracture”
How do plantar and penile fibromatoses present?
Plantar - thickened nodules of fibroblasts on plantar fascia of feet
Penile - thickening of tunica albuginea, leading to curvature of the shaft -> Peyronie disease
What are desmoid tumors also called and what their pattern of invasion? What age group gets them? Why are they difficult to manage?
Also called deep fibromatoses
They are locally aggressive and infiltrate fibroblastic lesions (more aggressive than superficial), but they are present in the deeper tissues.
Typically happen in adolescents / young adults
They are very difficult to easily excise.
Where do deep fibromatoses usually arise, in a broad sense?
Extra-abdominal - typically in large proximal muscle groups, very deep (i.e. thigh)
Abdominal - anterior abdominal wall muscles, associated with pregnancy
Intra-abdominal - often in the mesentery and the pelvis
What problems can intraabdominal deep fibromatoses cause and what condition are they associated with?
Can cause twisting and turning of the mesentery with bowel obstruction.
Associated with Gardner syndrome (an FAP variant also associated with osteomas of the face). Can be associated with any APC / B-catenin abnormalities.
What is nodular fasciitis and why is it scary?
A clonal proliferation of fibroblasts which enlarges very quickly, but it is benign and often spontaneously regresses. It looks mitotically active and you need to differentiate it from a fibrosarcoma.
Who tends to get nodular fasciitis and where does it appear?
Tends to occur in young adults as a rapidly-growing soft tissue mass usually on the extremities.
What is myositis ossificans a subtype of and what causes it?
Heterotopic ossification
It is more specifically heterotopic ossification within a muscle
Mesenchymal cells which would normally form granulation tissue after a trauma instead form fully differentiated bone (also mesenchymal origin) even replete with bone marrow, calcifying from periphery to center.
How is myositis ossificans usually diagnosed? Is it woven or lamellar bone?
Usually diagnosed by a radiologist. Easy to see the mineralized bone within the soft tissue on X-ray, and then that combined with a history of trauma which induced it will make you suspect it’s just heterotopic bone formation.
It is like normal bone -> first woven then replaced by lamellar
Are benign or malignant soft tissue tumors more common? Where do they usually arise?
Benign is more common
Benign - usually superficial (i.e. dermis or subcutaneous tissues)
Malignant - frequently in deep soft tissues of extremities (i.e. thighs) or retroperitoneum
What is the most common soft tissue tumor of adults?
Lipoma
-> well-circumscribed subcutaneous mass of normal appearing adipocytes
What is a benign fibrous histocytoma?
Also called dermatofibroma
Firm, mobile, well-defined dermal papule of short bundles of histiocyte-like cells swirling.
What is the defining clinical characteristic of dermatofibroma and who gets it? What’s the other name for it again?
Benign fibrous histiocytoma - Tends to be on the legs of young to middle-aged women.
Looks a bit like a melanoma, but DIMPLES with lateral compression
What are the two broad types of neurofibroma, and who can get them? What cell forms the tumor and does it invade the nerve or not?
- Cutaneous neurofibroma - can be sporadic, or very many if associated with NF-1
- Plexiform neurofibroma - only associated with NF-1
These are tumors of diverse cellular origins, and intercalate between fibers of the nerve -> removal will destroy nerve function
How are plexiform neurofibromas dealt with and why? Where are they found?
Most often found around major nerve trunk
They are removed because they cause pain, and have a risk of transforming into malignant peripheral nerve sheath tumor. Removal even though this destroys function.
What are the two growth patterns within a schwannoma? Does the tumor mass intermingle? What syndrome is it associated with?
Tumor mass is well demarcated and can be easily removed from the nerve (i.e. vestibular schwannoma) Associated with NF-2, loss of merlin.
Two growth patterns characterize it histologically:
Antoni A - Associated with Verocay bodies
Antoni B - Hypocellular regions with myxoid stroma
What are Verocay bodies?
Hypercellular regions composed of rows of palsading nuclei separated by bands of pink cytoplasmic processes (two stacks of cells lined up with pink between them)
Where do most malignant soft tissue neoplasms arise from and who tends to get them? How do they feel? What are their genomic characteristics?
They arise from pluripotent mesenchymal stem cells
They feel like “fish flesh” / squishy, unlike carcinomas which are more stiff due to desmoplasia, these have no desmoplasia.
They are usually diagnosed in middle aged / older adults, except rhabdomyosarcoma.
Genomic characteristics: most have a complex karyotype and are pleomorphic, suggesting genomic instability.
What is the single most common soft tissue malignancy of adults, and what cells are characteristic? Where does it arise?
Liposarcoma - a yellowish mass which contains lipoblasts -> cells composed of tiny vacuoles rather than large fat droplets
Arises where all soft tissues malignancies tend to: retroperitoneum or deep proximal muscles (i.e. thigh)
What mutation is commonly associated with some forms of liposarcoma?
amplification of a gene encoding p53 inhibitor -> allows cell to adopt the wild karyotypes we were talking about (DNA damage)
What is the most common group of adult soft tissue sarcomas and what does it look like grossly and microscopically?
Undifferentiated pleomorphic sarcoma
Looks underdifferentiated, pleomorphic, and mesenchymal-like
Grossly, it looks malignant with areas of hemorrhage and coagulation necrosis
Are leiomyomas and leiomyosarcomas unique to the uterus? What helps guide prognosis of the latter?
No, they too can arise in common spaces for benign or malignant neoplasms, respectively.
Prognosis of leiomyosarcoma, being a sarcoma, is based on number of mitoses per high power field as well as the stage
What is the most common childhood malignant soft tissue sarcoma? Where does it usually arise and what is it called if it does?
Rhabdomyosarcoma
Arises as a polypoid, grape-like mass in hollow, mucosa-lined cavities, i.e.:
Nasopharynx
Urinary bladder
Vagina - classic presentation
Called sarcoma botryoides
Oddly enough these are all areas where skeletal muscle is not normally present
What will the cells look like in sarcoma botryoides and how can they be identified?
This tumor is specifically an embryonal rhabdomyosarcoma. The cell type is “rhadomyoblast”
Immature skeletal muscle cells with eccentric nulcei. They will have a cross-striation pattern on histology and will stain positive for actin and myosin.
What is the type of rhabdomyosarcoma which is not embryonal? What is its growth pattern and where does it grow?
Alveolar rhabdomyosarcoma
-> tumor cells are on fibrous septae. Looks like alveoli
Arises in a location more typical for adult soft tissue malignancies: trunk and deep extremities.
May need to be differentiated from Ewing sarcoma based on absence of Codman’s triangles and onion skinning pattern because it’s invading inward not coming out.
What is the cell of derivation of synovial sarcoma and who gets it?
Occurs in young adults (in between children and normal older adults you see for sarcomas)
Cell of differentiation is UNKNOWN -> called synovial because it arises near synovial joints (especially the knee)
What is the pattern which synovial sarcoma grows?
Grows as a monophasic or biphasic malignancy. Very aggressive.
- Tightly packed spindle cells
+/- - Gland-like structures (reminiscent of synoviocytes)
Often with scattered calcifications
