Inflammatory Myofibroblastic Tumor
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Inflammatory myofibroblastic tumor (IMT) is a rare
neoplasm 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 ...
of the
mesodermal The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical Embr ...
cells that form the
connective tissue Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...
s which support virtually all of the organs and tissues of the body. IMT was formerly termed inflammatory pseudotumor. Currently, however, inflammatory pseudotumor designates a large and heterogeneous group of soft tissue tumors that includes inflammatory myofibroblastic tumor, plasma cell granuloma, xanthomatous pseudotumor, solitary mast cell granuloma, inflammatory fibrosarcoma, pseudosarcomatous myofibroblastic proliferation, myofibroblastoma, inflammatory myofibrohistiocytic proliferation, and other tumors that develop from connective tissue cells. Inflammatory pseudotumour is a generic term applied to various neoplastic and non-neoplastic tissue lesions which share a common microscopic appearance consisting of spindle cells and a prominent presence of the
white blood cells White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
that populate chronic or, less commonly, acute
inflamed Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', ''d ...
tissues. Inflammatory myofibroblastic tumor was initially regarded as a benign tumor that most often developed in the lung and less commonly in almost any organ system or tissue. Over time, however, IMT cases occurred in which the tumor spread into local tissues, metastasized to distal tissues, recurred after treatment, or consisted of neoplastic cells that had pro-malignant
chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...
abnormalities. Consequently, the
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
, 2013, and current literature commonly describe inflammatory myofibroblastic tumor as a neoplasm with intermediate malignant potential or a rarely metastasizing neoplasm. In 2020, the World Health Organization reclassified IMT as a specific tumor form in the category of intermediate (rarely metastasizing)
fibroblastic and myofibroblastic tumors Fibroblastic and myofibroblastic tumors (FMTs) are tumors which 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 ...
. In all events, IMT is a rare tumor with a reported incidence in 2009 of 150–200 cases/year in the United States. IMT lesions typically consist of, and are defined by, myofibrolastic spindle cells, i.e. specialized cells that are longer than wide, have a microscopic appearance that merges the appearances of
fibroblast A fibroblast is a type of cell (biology), biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and ...
s and
smooth muscle cell Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called becau ...
s (see
myofibroblast 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-s ...
), occur in normal as well as tumor tissues, and in normal tissues are commonly designated
fibroblasts A fibroblast is a type of biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibrobla ...
. However, the lesions in some IMF cases are dominated by sheets of epithelioid cells (which may have rounded shapes) with only a minor component of spindle cells. Tumors with these characteristics are regarded as a subtype of IMT termed epithelioid inflammatory myofibroblastic sarcoma (EIMS). The tumors in IMT and EIMS consistently contain
pro-inflammatory Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', ''d ...
white blood cells and in most cases tumor cells that express highly abnormal
oncogenic Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abno ...
(cancer-causing)
fusion protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this '' fusion gene'' ...
s such as those that contain the active portion of
anaplastic lymphoma kinase Anaplastic lymphoma kinase (ALK) also known as ALK tyrosine kinase receptor or CD246 (cluster of differentiation 246) is an enzyme that in humans is encoded by the ''ALK'' gene. Identification Anaplastic lymphoma kinase (ALK) was originally di ...
(ALK). It is not clear whether this inflammation, the genetic abnormalities, or both contribute to the development of IMT but drugs blocking the activities of the fusion proteins made by these genetic abnormalities may be useful in treating the disease.


Signs and symptoms

IMT was regarded as a tumor that occurs in children or young adults and presented in the lung,
mesentery In human anatomy, the mesentery is an Organ (anatomy), organ that attaches the intestines to the posterior abdominal wall, consisting of a double fold of the peritoneum. It helps (among other functions) in storing Adipose tissue, fat and allowi ...
,
greater omentum Greater may refer to: *Greatness, the state of being great *Greater than, in inequality * ''Greater'' (film), a 2016 American film *Greater (flamingo), the oldest flamingo on record * "Greater" (song), by MercyMe, 2014 * Greater Bank, an Australi ...
or, less commonly, heart, liver, spleen, pancreas, colon, small intestine,
spermatic cord The spermatic cord is the cord-like structure in males formed by the vas deferens (''ductus deferens'') and surrounding tissue that runs from the deep inguinal ring down to each testicle. Its serosal covering, the tunica vaginalis, is an exten ...
, prostate, uterus, eye orbit,
peripheral A peripheral device, or simply peripheral, is an auxiliary hardware device that a computer uses to transfer information externally. A peripheral is a hardware component that is accessible to and controlled by a computer but is not a core compo ...
or
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
nerves, brain
meninges In anatomy, the meninges (; meninx ; ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in the subarachnoid spac ...
,
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...
, or other sites. However, a more recent retrospective study of 92 patients accumulated by the
Surveillance, Epidemiology, and End Results The Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NCI) is a source of epidemiologic information on the incidence and survival rates of cancer in the United States. The Program SEER collects and pub ...
(SEER) program of the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
found the mean age of disease onset was 47.4 years with peak occurrences at 0 to 4, 36 to 40, and >50 years old; middle-aged individuals (41 to 64 years) represented 1/3 of all cases. In this study, the commonest sites of tumor occurrence were the lower limb and hip (22% of cases), upper limb and shoulder (12% of cases), and head, face, and neck (9% of cases). Another recent study of 25 patients found the commonest sites of IMT were the abdomen (40% of cases) and lung/thoracic wall (32% of cases). Individual IMT cases are also reported to present in the
urinary bladder The bladder () is a hollow organ in humans and other vertebrates that stores urine from the Kidney (vertebrates), kidneys. In placental mammals, urine enters the bladder via the ureters and exits via the urethra during urination. In humans, the ...
,
anal canal The anal canal is the part that connects the rectum to the anus, located below the level of the pelvic diaphragm. It is located within the anal triangle of the perineum, between the right and left ischioanal fossa. As the final functional s ...
, and parameningeal spaces (i.e. sites adjacent to the meninges such as the
nasopharynx The pharynx (: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the esophagus and trachea (the tubes going down to the stomach and the lungs respectively). It is found in vertebrates and invertebrates, though its ...
,
middle ear The middle ear is the portion of the ear medial to the eardrum, and distal to the oval window of the cochlea (of the inner ear). The mammalian middle ear contains three ossicles (malleus, incus, and stapes), which transfer the vibrations ...
,
paranasal sinuses Paranasal sinuses are a group of four paired air-filled spaces that surround the nasal cavity. The maxillary sinuses are located under the eyes; the frontal sinuses are above the eyes; the ethmoidal sinuses are between the eyes and the sphe ...
,
infratemporal fossa The infratemporal fossa is an irregularly shaped cavity that is a part of the skull. It is situated below and medial to the zygomatic arch. It is not fully enclosed by bone in all directions. It contains superficial muscles, including the lower ...
and
pterygopalatine fossa In human anatomy, the pterygopalatine fossa (sphenopalatine fossa) is a fossa in the skull. A human skull contains two pterygopalatine fossae—one on the left side, and another on the right side. Each fossa is a cone-shaped paired depression dee ...
). Apparently, the age and organ/tissue distribution of IMT various with the patient population examined: in general it can present in individuals of almost any age and in almost any organ or tissue site. IMT most commonly presents as a tumor localized to a single site but may be associated with distal
metastases Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
in up to 5% of all cases or up to 10% of cases in which the tumor cells express an ALK fusion protein. The tumors range in size from 1–25 cm (average 6.5 cm) with two-thirds being 1.5–6.5 cm. In rare cases, the tumors have spontaneously regressed. Individuals with IMT present with a wide range of symptoms (e.g. pain, swelling, a mass, organ dysfunction, etc.) depending on the tumor location(s). Up to 1/3 of these individuals have symptoms of systemic inflammation such as fever, chills,
night sweats Night sweats or nocturnal hyperhydrosis is the repeated occurrence of excessive sweating during sleep. The person may or may not also perspire excessively while awake. One of the most common causes of night sweats in women over 40 is the horm ...
, and weight loss. Rare cases of IMT have developed in individuals with: a) organizing
pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...
; b) infection by '' Mycobacterium avium intracellulare'' or ''
Corynebacterium equi ''Rhodococcus equi'' is a Gram-positive coccobacillus bacterium. The organism is commonly found in dry and dusty soil and can be important for diseases of domesticated animals (horses and goats). The frequency of infection can reach near 60%. '' ...
'' (pneumonia-causing bacteria); ''
Campylobacter jejuni ''Campylobacter jejuni'' is a species of pathogenic bacteria that is commonly associated with poultry, and is also often found in animal feces. This species of microbe is one of the most common causes of food poisoning in Europe and in the US, w ...
'' (causes
gastroenteritis Gastroenteritis, also known as infectious diarrhea, is an inflammation of the Human gastrointestinal tract, gastrointestinal tract including the stomach and intestine. Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of ...
); ''
Lysinibacillus sphaericus ''Lysinibacillus sphaericus'' (previously known as ''Bacillus sphaericus'') is a Gram-positive, mesophilic, rod-shaped bacterium commonly found on soil. It can form resistant endospores that are tolerant to high temperatures, chemicals and ultrav ...
'' (previously termed ''Bacillus sphaericus'', a rare cause of lung infections and
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
); '' Coxiella burneti'' (causes
Q fever Q fever or query fever is a disease caused by infection with ''Coxiella burnetii'', a bacterium that affects humans and other animals. This organism is uncommon, but may be found in cattle, sheep, goats, and other domestic mammals, including ...
);
Epstein–Barr virus The Epstein–Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), is one of the nine known Herpesviridae#Human herpesvirus types, human herpesvirus types in the Herpesviridae, herpes family, and is one of the most common viruses in ...
(causes
infectious mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adu ...
and Epstein–Barr virus-associated lymphoproliferative malignant diseases); and
E. coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escherichia'' that is commonly foun ...
-related occlusive
phlebitis Phlebitis (or venitis) is inflammation of a vein, usually in the legs. It most commonly occurs in superficial veins. Phlebitis often occurs in conjunction with thrombosis (clotting inside blood vessels) and is then called thrombophlebitis or ...
of intrahepatic veins; or c) previous abdominal surgery; trauma; ventriculoperitoneal shunt in the brain; radiation therapy; and
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...
usage. The relationship (i.e. cause or merely association) of these disease relationships to IMT is unknown.


Molecular abnormalities

The neoplastic cells in 50–60% of IMT and all cases of EIMS express an abnormal ALK protein made by a
somatic recombination Somatic recombination, as opposed to the genetic recombination that occurs in meiosis, is an alteration of the DNA of a somatic cell that is inherited by its daughter cells. The term is usually reserved for large-scale alterations of DNA such as ch ...
in the ''ALK''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. ALK, i.e. anaplastic lymphoma kinase (also termed protein kinase B), is produced by the ''ALK'' gene. In IMT, the ''ALK'' gene has
merged Mergers and acquisitions (M&A) are business transactions in which the ownership of a company, business organization, or one of their operating units is transferred to or consolidated with another entity. They may happen through direct absorpt ...
with a gene located at another site on the same or different chromosome to form a
chimeric gene Chimeric genes (literally, made of parts from different sources) form through the combination of portions of two or more coding sequences to produce new genes. These mutations are distinct from fusion genes which merge whole gene sequences into ...
consisting of a part of the new gene and a part of the ''ALK'' gene coding for ALK's activity. This chimeric gene overproduces a
fusion protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this '' fusion gene'' ...
with excessive ALK activity. ALK is a
serine/threonine-specific protein kinase A serine/threonine protein kinase () is a kinase enzyme, in particular a protein kinase, that phosphorylation, phosphorylates the hydroxyl, OH group of the amino acid, amino-acid residues serine or threonine, which have similar side chains. ...
that directly or indirectly stimulates PI3K/AKT/mTOR,
Ras GTPase Ras, from "Rat sarcoma virus", is a family of related proteins that are expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals ...
, ERKs,
Janus kinase Janus kinase (JAK) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 and 2 (since they were just two of many discoverie ...
,
STAT protein STAT, Stat., or stat may refer to: * stat (system call), a Unix system call that returns file attributes of an inode * ''Stat'' (TV series), an American sitcom that aired in 1991 * Stat (website), a health-oriented news website * STAT protein, ...
s, and other
cell signaling In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...
elements. Activation of these elements stimulates cell growth, proliferation, survival, and other tumor-promoting behaviors. As an example of this
chromosomal translocation In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes "balanced" and "unbalanced" translocation, with three main types: "reciprocal", "nonreciprocal" and "Robertsonian" transloc ...
, the ''ALK'' gene located on the short or "p" arm of chromosome 2 at position 23 (notated as 2p23) merges with the ''
CLTC Clathrin heavy chain 1 is a protein that in humans is encoded by the ''CLTC'' gene. Clathrin is a major protein component of the cytoplasmic face of intracellular organelles, called coated vesicles and coated pits. These specialized organelles ...
'' gene on the long, i.e. "q" arm of chromosome 17 at position 13 (notated 17q23) to form a chimeric gene notated as t(2;17)(p23;q23). This chimeric gene makes a CLTC-ALK fusion protein with uncontrolled ALK serine/threonine-specific protein kinase activity. Other genes that fuse with AKT found in IMT include: '' TFG,
DCTN1 Dynactin subunit 1 is a protein that in humans is encoded by the ''DCTN1'' gene. Function This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 23 subunits (11 individual proteins ranging in size from 22 ...
, EML4,
TPM3 Tropomyosin alpha-3 chain is a protein that in humans is encoded by the ''TPM3'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is ...
'', ''
TPM4 Tropomyosin alpha-4 chain is a protein that in humans is encoded by the ''TPM4'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is ...
'', ''ATIC'' ''
RANBP2 RAN binding protein 2 (RANBP2) is protein which in humans is encoded by the ''RANBP2'' gene. It is also known as nucleoporin 358 (Nup358) since it is a member nucleoporin family that makes up the nuclear pore complex. RanBP2 has a mass of 358 kDa ...
'' (most if not all ''RAMB2-ALK'' chimeric genes occur in the EMIS form of IMT), ''CARS1'', and ''SEC31L1''. IMT cases may express other chimeric genes in which the active parts of
ROS1 Proto-oncogene tyrosine-protein kinase ROS is an enzyme that in humans is encoded by the ''ROS1'' gene. Function This proto-oncogene, highly expressed in a variety of tumor cell lines, belongs to the sevenless subfamily of tyrosine kinase ins ...
(found in 10% of IFT cases and coding for a
tyrosine kinase A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger cla ...
which promotes cell growth),
PDGFRB Platelet-derived growth factor receptor beta is a protein that in humans is encoded by the ''PDGFRB'' gene. Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies. Gene The ''PDGFRB'' gene is located on h ...
(coding for a protein that may promote the development of cancer), and '' NTRK'' (coding for a
receptor tyrosine kinase Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinas ...
that may promote the development of cancer) merge with other genes. The fusion protein products of these chimeric genes, like those of ALK fusion proteins, are overproduced, overactive, and thereby may contribute to the development of IMT.


Diagnosis

Histopathologic Histopathology (compound of three Greek language, Greek words: 'tissue', 'suffering', and ''-logy, -logia'' 'study of') is the light microscope, microscopic examination of Tissue (biology), tissue in order to study the manifestations of dis ...
examination of the tumors in IMT generally reveals myofibroblastic spindle cell sheets in a myxoid background (i.e. a background matrix containing gelatinous
mucopolysaccharide Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long-chain polymeric carbohydrates composed of monosacchari ...
s and non-sulfated
glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case o ...
s); the matrix also contains inflammatory cells, particularly
plasma cells Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances c ...
and
lymphocytes A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), and ...
occasionally mixed with
eosinophils Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along wi ...
and
neutrophils Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in different ...
. The epithelioid inflammatory myofibroblastic sarcoma subtype of IMT shows sheets of epithelioid to round cells within a myxoid (i.e. appears blue or purple compared to the normal red appearance of connective tissue when appropriately
H&E stain Hematoxylin and eosin stain ( or haematoxylin and eosin stain or hematoxylin–eosin stain; often abbreviated as H&E stain or HE stain) is one of the principal tissue stains used in histology. It is the most widely used stain in medical diag ...
ed and examined under the microscope), collagenous, or mixed myxoid-collagenous matrix, <5% spindle cells, and an inflammatory cell infiltrate that in most cases consists predominantly of neutrophils or, less often, small lymphocytes or eosinophils; plasma cells occur in only a minority of EIMS cases. The neoplastic cells in the tumors of 50% to 60% of IMT cases and 100% of EIMS cases express an ALK fusion protein. Other genetic abnormalities occur in these cells. Testing for the presence of the ALK fusion protein and other genetic abnormalities (see next section) can help diagnose IMT.


Treatment

Many sources recommend that localized IMT be treated with total resection of all tumorous tissues. Localized tumor recurrences may likewise be treated by total resection. There is little support for adding radiation or systemic chemotherapy to this regimen. Tumors that are not resectable, occur in inaccessible sites, are multifocal, or have metastasized are treated with aggressive therapeutic regimens. In one retrospective study, 59 patients (all <25 years old) with IMT where treated with surgery. 31 had no residual disease post-surgery; 4 of these patients had local relapses, 3 of whom were again treated surgically and 1 with surgery plus chemotherapy. Nineteen had microscopic residual disease post-surgery. Post-surgery, 6 of these patients were treated with high-dose
corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...
; 5 with
vinblastine Vinblastine, sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small-cell lung cancer, bladder canc ...
+
methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
; 3 with inhibitors of ALK; 2 with
vinorelbine Vinorelbine, sold under the brand name Navelbine among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer and non-small cell lung cancer. It is given by injection into a vein or by mout ...
+ low-dose
cycloheximide Cycloheximide is a naturally occurring fungicide produced by the bacterium '' Streptomyces griseus''. Cycloheximide exerts its effects by interfering with the translocation step in protein synthesis (movement of two tRNA molecules and mRNA in re ...
or
Ifosfamide Ifosfamide, sold under the brand name Ifex among others, is a chemotherapy medication used to treat a number of types of cancer. This includes testicular cancer, soft tissue sarcoma, osteosarcoma, bladder cancer, small cell lung cancer, c ...
-based chemotherapy; and 1 with cyclophosphamide + vinchristine +
actinomycin D Dactinomycin, also known as actinomycin D, is a chemotherapy medication used to treat a number of types of cancer. This includes Wilms tumor, rhabdomyosarcoma, Ewing's sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of o ...
chemotherapy. Of these 19 patients, 4 had complete responses, 8 partial responses, 5 stable disease, and 2 progressive disease. Nine patients had macroscopic disease post-surgery; 5 of these patients received vincristine + methotrexate; 2 received ALK inhibitors; and 1 each received either high-dose corticosteroids or Ifosfamide-based chemotherapy. Of these 9 patients, none had complete responses; 6 had partial responses; 1 had steady disease; and 2 had progressive disease. There were no deaths among the 59 patients. The various drug regimens showed little differences in effectiveness although patients treated with ALK inhibitors trended to have longer response times. Another retrospective study evaluated the response of 17 patients (aged 22–46 years; median age 32 years) with advanced disease to Adriamycin-based chemotherapy regimens, i.e. Adriamycin alone, Adriamycin + Ifosfamide, or Adriamicin + other chemotherapy drugs. No patients had a complete response, 8 patients had partial responses, 4 patients had steady disease, and 5 patients had progressive disease. Progression-free survival and overall survival times for the group were 6.6 and 21.2 months, respectively. The study also evaluated 9 patients (aged 12–31 years, median age 16) treated with methotrexate + vinblastine, methotrexate +
vinorelbine Vinorelbine, sold under the brand name Navelbine among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer and non-small cell lung cancer. It is given by injection into a vein or by mout ...
, or vinblastine + vinorelbine; 2 patients attained complete responses, 3 attained partial responses, 2 had steady disease, and 2 had progressive disease; this groups' progression-free time was not reached while its overall survival time was 83.4 months. The study concluded that the Adriamycin-based and methotrexate/vinblastine/vinorelbine regimens have a high degree of activity in IMT. Due to the low numbers of patients evaluated, no conclusions could be made on which regimen(s) were most effective. In addition to the report that compared the effect of ALK-inhibitors to other therapy regimens detailed in the previous paragraph, several reports have focused primarily on small numbers of IMT patients treated with an ALK inhibitor. The
European Organisation for Research and Treatment of Cancer The European Organisation for Research and Treatment of Cancer (EORTC) is a unique pan-European non-profit clinical cancer research organisation established in 1962 operating as an international association under Belgium law. It develops, conduc ...
evaluated the effect of the ALK-inhibitor,
crizotinib Crizotinib, sold under the brand name Xalkori among others, is an anti-cancer medication used for the treatment of non-small cell lung carcinoma (NSCLC). Crizotinib inhibits the c-Met/ Hepatocyte growth factor receptor (HGFR) tyrosine kinase, wh ...
, on 12 ALK-positive IMT adults who had persistent and/or metastatic disease following surgical and/or drug treatment: 2 patients had complete responses, 4 had partial responses, 5 had steady disease, and none had progressive disease; 9 of these patients had at least 1 year of progression-free survival but one patient died of the disease. A review of previously published IMT patients of all ages found that: 1) 4 patients (3 with unifocal, 1 with multifocal disease) without prior treatment had complete responses to crizotinin; 2) 2 patients (1 with unifocal, 1 with multifocal disease) that had persistent disease after surgery and previously treated with chemotherapy had partial responses to crizotinib while 1 patient previously treated with a
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...
,
prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...
, continued to have progressive disease on crizotinib; and 3) 6 patients with progressive disease after surgery (due to multifocal or unifocal disease in inaccessible sites) had complete responses (2 cases), partial responses (2 cases), stable disease (1 case), or progressive disease (1 case) in response to crizotinib. Two of these crizotinib-treated patients with progressive disease had near complete responses to second generation ALK inhibitors Another study reviewed 29 pediatric patients (age 15 months to 17 years) who were treated with an ALK inhibitor followed by surgical removal of the tumor (5 cases), surgical tumor removal followed by an ALK inhibitor (12 cases), or an ALK inhibitor without surgery. Twelve patients had complete responses, 14 partial responses, 2 stable disease, and 2 recurrences after finishing ALK inhibitor treatment. The latter two patients obtained complete responses to retreatment with crizotinib (1 case) or a second generation ALK inhibitor, ceritinib (1 case). A study of 14 pediatric patients with metastatic or inoperable ALK-positive IMT were treated with crizotinib: 5 patients obtained complete responses, 7 partial responses, and 2 stable disease. Over the study period (2–63 months), no patient developed progressive disease. Numerous
Medical history The medical history, case history, or anamnesis (from Greek: ἀνά, ''aná'', "open", and μνήσις, ''mnesis'', "memory") of a patient is a set of information the physicians collect over medical interviews. It involves the patient, and ev ...
studies have had similar results in treated IMT with ALK inhibitors. However, ALK inhibitors have serious side effects; in on study, crizotinib treatment was associated with pneumonia, fever of unknown cause, heart attack,
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
, abdominal
abscess An abscess is a collection of pus that has built up within the tissue of the body, usually caused by bacterial infection. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pre ...
, acute renal insufficiency, and the development of an abnormal EKG (i.e.
QT prolongation QT or Qt may refer to: Businesses * The Qt Company, a Finnish software developer * QT Hotels & Resorts, an Australasian hospitality provider * QT Inc., an American bracelet manufacturer * QuikTrip, an American convenience store chain People * ...
).
Entrectinib Entrectinib, sold under the brand name Rozlytrek, is an anti-cancer medication used to treat ROS1-positive non-small cell lung cancer and NTRK fusion-positive solid tumors. It is a selective tyrosine kinase inhibitor (TKI), of the tropomyosin ...
, a tyrosine kinase inhibitor that is active on ROS1 and NRTK as well as AKT, has shown clinically significant activity in individual cases of patients with IMT expressing ROS1, NRTK, and/or an ALK fusion proteins.


See also

* Anaplastic lymphoma kinase-positive neoplasias *
ALK inhibitor ALK inhibitors are anti-cancer drugs that act on tumours with variations of anaplastic lymphoma kinase (ALK) such as an EML4- ALK translocation. They fall under the category of tyrosine kinase inhibitors, which work by inhibiting proteins involv ...
s * Inflammatory myeloblastic tumor


References

DEMIR, Ömer Faruk, et al. Surgical treatment outcomes of pulmonary inflammatory myofibroblastic tumors. Annals of Thoracic Medicine, 2022, 17.1: 44.


External links

{{Medical resources , DiseasesDB = , ICD10 = , ICD9 = , ICDO = {{ICDO, 8825, 1 , OMIM = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = , Orphanet = 178342 Soft tissue disorders IgG4-related disease