Ischemic fasciities (IF), also termed atypical decubital fibroplasia
or decubital ischemic fasciitis,
is a rare pseudosarcomatous (i.e. easily mistaken for a
sarcoma
A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcom ...
) tumor. It was first described by E. A. Montgomery et al. in 1992.
This tumor typically forms in the
subcutaneous tissue
The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and macr ...
s (i.e. lower most tissue layer of the skin) that overlie bony protuberances such as a hip in individuals who are debilitated and bed-ridden.
Microscopically, IF lesions consist of proliferating, atypical
fibroblasts
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells o ...
and/or
myofibroblasts
A myofibroblast is a cell phenotype that was first described as being in a state between a fibroblast and a smooth muscle cell.
Structure
Myofibroblasts are contractile web-like fusiform cells that are identifiable by their expression of α-sm ...
. The lesions were initially regarded as non-
neoplastic
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
proliferation responses of these cell types to long-term tissue pressure or trauma.
More recently, however, the
World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
, 2020, defined IF lesions as
neoplasms
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
, i.e. tissue growths which are uncoordinated with that of the normal surrounding tissue and persist in growing even if the original trigger for their development is removed. The Organization formally classified IF lesions as belonging to the category of
benign
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malign ...
fibroblastic and myofibroblastic tumors
Fibroblastic and myofibroblastic tumors (FMTs) develop from the mesenchymal stem cells which differentiate into fibroblasts (the most common cell type in connective tissue) and/or the myocytes/myoblasts that differentiate into muscle cells. FMTs ...
.
The treatment of choice for these often disfiguring, uncomfortable, and/or painful IF tumors is generally conservative, local surgical excision.
It is critically important that these benign tumors be distinguished from other
fasciitis
Fasciitis is an inflammation of the fascia, which is the connective tissue surrounding muscles, blood vessels and nerves.
In particular, it often involves one of the following diseases:
* Necrotizing fasciitis
* Plantar fasciitis
Plantar f ...
tumors as well as certain
sarcoma
A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcom ...
s which can be highly invasive and/or malignant and therefor require far more aggressive treatment.
Presentation
In the original study of IF, individuals diagnosed with the disorder were women (16 cases) or men (12 cases) age 15 to 95 years;
In a more recent study, diagnosed individuals were women (15 cases) or men (29 cases) aged 23–96 years old.
Most individuals in these two studies were in their 8th or 9th decade when diagnosed with IF and, overall, had a relatively long history of being invalided, immobilized, and/or bed-ridden due to other disorders such as severe
osteoarthritis
Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...
,
rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
,
chronic renal failure
Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...
,
chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...
, cancer,
or
dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
.
In the study of 44 individuals, however, an appreciable number of patients did not have a history of debilitation.
Some individuals reported that they had prior trauma in the areas where their lesions developed.
Individuals present with a painless
or painful
and sometimes disabling
slowly growing mass
that is ill-defined, located in deep subcutaneous tissues, and, rarely, has spread into an adjacent
skeletal muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
or tendon. The masses vary from 1.3 to 10 cm in maximum diameter.
In the study of 44 cases, 76.7% of the tumors were located around the base of a hip (11 cases), shoulder (7 cases), or
greater trochanter
The greater trochanter of the femur is a large, irregular, quadrilateral eminence and a part of the skeletal system.
It is directed lateral and medially and slightly posterior. In the adult it is about 2–4 cm lower than the femoral head.Stan ...
of the
femur
The femur (; ), or thigh bone, is the proximal bone of the hindlimb in tetrapod vertebrates. The head of the femur articulates with the acetabulum in the pelvic bone forming the hip joint, while the distal part of the femur articulates with ...
; 4 were in a hip joint, 4 in a thigh, 3 in the
iliac crest
The crest of the ilium (or iliac crest) is the superior border of the wing of ilium and the superiolateral margin of the greater pelvis.
Structure
The iliac crest stretches posteriorly from the anterior superior iliac spine (ASIS) to the posterior ...
, 2 in a
buttock
The buttocks (singular: buttock) are two rounded portions of the exterior anatomy of most mammals, located on the posterior of the pelvic region. In humans, the buttocks are located between the lower back and the perineum. They are composed ...
, and 1 each in the
lumbar
In tetrapod anatomy, lumbar is an adjective that means ''of or pertaining to the abdominal segment of the torso, between the diaphragm and the sacrum.''
The lumbar region is sometimes referred to as the lower spine, or as an area of the back i ...
region,
scapular region, or a
deltoid muscle
The deltoid muscle is the muscle forming the rounded contour of the human shoulder. It is also known as the 'common shoulder muscle', particularly in other animals such as the domestic cat. Anatomically, the deltoid muscle appears to be made up o ...
; in the remaining cases, ~11.2% of the tumors were on the chest wall away from the shoulders and ~11.2% were on the back.
Typically, the tumors reside over boney protuberances which, it is thought, provide the mechanical pressures that cause poor blood flow to nearby subcutaneous tissues, aberrant wound healing in these tissues, and thereby the development of IF.
Pathology
On gross examination, IF tumors are typically white-yellow masses with central necrosis (i.e. areas of dead or dying cells), and areas containing
cyst
A cyst is a closed sac, having a distinct envelope and cell division, division compared with the nearby Biological tissue, tissue. Hence, it is a cluster of Cell (biology), cells that have grouped together to form a sac (like the manner in which ...
s and/or old, dried
hemorrhage
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
s.
The tumors are often poorly circumscribed, have an infiltrative appearance, may be multinodular, and lie in subcutaneous tissue but may also involve the
dermal
The dermis or corium is a layer of skin between the epidermis (with which it makes up the cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from stress and strain. It is divided ...
layer of the skin
and/or the
reticular dermis
The dermis or corium is a layer of skin between the epidermis (with which it makes up the cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from stress and strain. It is divided in ...
.
Microscopic
The microscopic scale () is the scale of objects and events smaller than those that can easily be seen by the naked eye, requiring a lens (optics), lens or microscope to see them clearly. In physics, the microscopic scale is sometimes regarded a ...
histopathological
Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spec ...
studies of IF tissues report the characteristic presence of a distinct zonal appearance, i.e. the presence of central zones of
fibrinoid necrosis
Fibrinoid necrosis is a specific pattern of irreversible, uncontrolled cell death that occurs when antigen-antibody complexes are deposited in the walls of blood vessels along with fibrin. It is common in the immune-mediated vasculitides which a ...
and areas of cyst-laden necrosis in a hypocellular background surrounding by a zone of
granulation tissue
Granulation tissue is new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process. Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size ...
(i.e. connective tissue containing microscopic blood vessels) populated by atypical, swollen fibroblasts, myofibroblasts, and/or
macrophages
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
.
Immunohistochemistry
Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to an ...
analyses of IF tumors often show the presence of fibroblasts, fibroblast-like cells, and or other types of cells that in a percentage of cases express
smooth muscle actin
Smooth may refer to:
Mathematics
* Smooth function, a function that is infinitely differentiable; used in calculus and topology
* Smooth manifold, a differentiable manifold for which all the transition maps are smooth functions
* Smooth algebrai ...
proteins,
CD68
CD68 ( Cluster of Differentiation 68) is a protein highly expressed by cells in the monocyte lineage (e.g., monocytic phagocytes, osteoclasts), by circulating macrophages, and by tissue macrophages (e.g., Kupffer cells, microglia).
Structure a ...
protein,.
desmin
Desmin is a protein that in humans is encoded by the ''DES'' gene. Desmin is a muscle-specific, type III intermediate filament that integrates the sarcolemma, Z disk, and nuclear membrane in sarcomeres and regulates sarcomere architecture.
Str ...
protein,
vimentin
Vimentin is a structural protein that in humans is encoded by the ''VIM'' gene. Its name comes from the Latin ''vimentum'' which refers to an array of flexible rods.
Vimentin is a type III intermediate filament (IF) protein that is expressed ...
protein, and
collagen type IV
Collagen IV (ColIV or Col4) is a type of collagen found primarily in the basal lamina. The type IV collagen C4 domain, collagen IV C4 domain at the C-terminus is not removed in post-translational processing, and the fibers link head-to-head, rathe ...
protein, but not
keratin
Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, ho ...
,
S100,
calponin
Calponin is a calcium binding protein. Calponin tonically inhibits the ATPase activity of myosin in smooth muscle. Phosphorylation of calponin by a protein kinase, which is dependent upon calcium binding to calmodulin, releases the calponin's ...
, or
CD34
CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.
CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first descri ...
proteins.
The finding that a tumor's cells have some of these patterns of protein expression can help support the diagnosis of IF.
Gene and chromosome abnormalities
A single case of IF was found to have tumor cells bearing
chromosomal translocation
In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translo ...
s between chromosomes 1 and 2 and/or chromosomes 7 and 19. While further studies are needed to confirm these finding and to conduct further gene and chromosome analyses, these results support the notion that IF tumors are neoplasms rather than purely reactive lesions.
Diagnosis
IF tumors have features which overlap other types of
fasciitis
Fasciitis is an inflammation of the fascia, which is the connective tissue surrounding muscles, blood vessels and nerves.
In particular, it often involves one of the following diseases:
* Necrotizing fasciitis
* Plantar fasciitis
Plantar f ...
disorders such as
proliferative fasciitis and
nodular fasciitis
Nodular fasciitis (NF) is a benign, soft tissue tumor composed of myofibroblasts (i.e. immature cells that contain features of myocytes and fibroblasts) that typically occurs in subcutaneous tissue (i.e. lowermost layer of the skin), fascia (i. ...
. However, the age, history of debilitation, tumor location over boney protuberances, and tumor histopathology of having two distinctly different zones tend to distinguish IF from these two as well as the following tumors.
Decubitus ulcers
Pressure ulcers, also known as pressure sores, bed sores or pressure injuries, are localised damage to the skin and/or underlying tissue that usually occur over a bony prominence as a result of usually long-term pressure, or pressure in combi ...
, i.e. common bed sores, differ from IF in typically having extensive ulcerations of the skin and histopathological evidence of
acute inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
as determined by the presence of various types of
white blood cells
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
.
IF has also been mistaken for
epithelioid sarcoma
Epithelioid sarcoma is a rare soft tissue sarcoma arising from mesenchymal tissue and characterized by epithelioid-like features. It accounts for less than 1% of all soft tissue sarcomas. It was first clearly characterized by F.M. Enzinger in 197 ...
and
elastofibroma dorsi
Elastofibroma dorsi is an ill-defined fibroelastic tumor-like condition made up of enlarged and irregular elastic fibers. The World Health Organization, 2020, has classified elastofibroma tumors as one specific type of the fibroblastic and myofibr ...
. IF differs form epithelioid sarcoma by its clinical presentation, typical tumor cell
morphology
Morphology, from the Greek and meaning "study of shape", may refer to:
Disciplines
* Morphology (archaeology), study of the shapes or forms of artifacts
* Morphology (astronomy), study of the shape of astronomical objects such as nebulae, galaxies ...
, i.e. round cells with atypical
nuclei and eosinophilic
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
,
and complete or relative lack of necrotic areas.
Elastofibroma dorsi is distinguished from IF by its abundant content of
elastic fibers
Elastic fibers (or yellow fibers) are an essential component of the extracellular matrix composed of bundles of proteins (elastin) which are produced by a number of different cell types including fibroblasts, endothelial, smooth muscle, and air ...
.
Treatment
IF tumors are commonly treated by surgical excision although in rare cases these tumors have recurred at the site of their removal. Recurrent tumors have been treated by repeated surgical excisions.
Since IF tumors have not been reported to metastasize and no deaths have been attributed to it,
long-term clinical observation without surgical intervention is a reasonable alternative to surgery, particularly for IF tumors that are neither uncomfortable, painful, or disfiguring.
References
{{reflist
Connective and soft tissue neoplasms
Soft tissue disorders
Dermal and subcutaneous growths
Disorders of fascia
Benign neoplasms