Inflammatory myofibroblastic tumor is sometimes known as inflammatory pseudotumor tumor (IPT). It is a lesion of unknown etiology that has been reported in numerous anatomic sites. By definition, the tumor is composed of a dominant spindle cell proliferation with a variable inflammatory component. These spindle cells are now known to be myofibroblasts and this is the reason for the current designation for this disease. Inflammatory may not be applicable to all tumors since some investigators have demonstrated the presence of chromosomal abnormalities and documented cases showing aggressive behavior supporting the theory that at least some of these tumors are true neoplasms.
The tumor is more common in women, who often present with fever of unknown origin or other vague, nonspecific symptoms. Splenomegaly is a frequent finding.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Inflammatory pseudotumor
Plasma cell granuloma
SEX (M:F) Women more common
PATHOGENESIS CHARACTERIZATION GENERAL Myofibroblastic tumours: neoplasias with divergent behaviour: ultrastructural and flow cytometric analysis Pathol Res Pract 1999;195:619–632 Omental-mesenteric inflammatory pseudotumor: cytogenetic demonstration of genetic changes and monoclonality in one tumor Cancer 1994;73:1433–1437 EPSTEIN-BARR VIRUS Hum Pathol 1995;26:1093–1098.
Arch Pathol Lab Med 125:379–385, 2001
Association with EBV by immunohistochemical studies in 2 of 12 cases and by in situ hybridization in 6 of 10 cases
These findings corroborate with others who found an association with EBV in 4 of 6 splenic tumors and 1 of 2 liver tumors
- Absence of human herpesvirus-8 in pulmonary inflammatory myofibroblastic tumor: immunohistochemical and molecular analysis of 20 cases.
1Department of Pulmonary and Mediastinal Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.
- Mod Pathol. 2007 Sep;20(9):995-9. Abstract quote
Inflammatory myofibroblastic tumors are uncommon lesions composed of spindled myofibroblasts within a variable background of collagen and inflammatory cells. Although the true nature of these lesions is not fully elucidated, identification of consistent cytogenetic alterations in the anaplastic lymphoma kinase (ALK) gene suggests that they may be neoplastic. A small number of inflammatory myofibroblastic tumors have been reported to harbor human herpesvirus-8 (HHV-8), implicating the virus in its pathogenesis.
In this study, 20 cases of pulmonary inflammatory myofibroblastic tumor were analyzed for the presence of HHV-8 with immunohistochemical and molecular methods. In all cases, antibodies to the latent nuclear antigen of the virus were applied. Four open reading frames (ORFs), including ORFs K2, 16, 26, and 72, were targeted utilizing real-time polymerase chain reaction (PCR). The cohort included 9 men and 11 women with a mean age of 37 years (range, 1-81).
Microscopically, the tumors were composed of cytologically bland spindle cells with myofibroblastic differentiation. On immunohistochemical studies, 20% of cases (4/20) demonstrated diffuse cytoplasmic positivity with ALK. Immunohistochemical staining for the latent nuclear protein of the virus was negative in all cases (0/20). All tumors (100%, 20/20) tested with real-time PCR were negative for all four ORFs, whereas 100% (10/10) of positive control Kaposi sarcoma cases were positive. Her2 gene expression was present in all (20/20) inflammatory myofibroblastic tumors confirming the presence of amplifiable deoxyribonucleic acid in the tissue lysate.
This study documents the absence of HHV-8 in pulmonary inflammatory myofibroblastic tumors, suggesting that further investigation is required to clarify the pathogenesis of this lesion.
Human Herpesvirus-8 Genes Are Expressed in Pulmonary Inflammatory Myofibroblastic Tumor (Inflammatory Pseudotumor)
José Javier Gómez-Román, etal.
Am J Surg Pathol 2001;25:624-629 Abstract quote
The presence of human herpesvirus-8 DNA sequences, as well as an overexpression of human interleukin-6 and human cyclin D1 in myofibroblastic cells of inflammatory myofibroblastic tumor (inflammatory pseudotumor), has recently been reported.
We describe the pattern of human herpesvirus-8 gene expression in five cases of pulmonary inflammatory myofibroblastic tumor. Reverse transcriptase–polymerase chain reaction (RT-PCR), with several positive and negative controls, was performed to detect mRNA of 11 open reading frames encoded by human herpesvirus-8 in lytic and latent stages of viral replicative cycle.
We found molecular transcripts from ORF16, ORFK13, and ORF72 in the five cases and from ORFK2 in four of five neoplasms. The corresponding encoded proteins were human homologous oncoproteins (viral cyclin-D), inflammatory cytokines (viral IL-6), and inhibitors of apoptotic pathways (viral FLIP and viral Bcl-2), mostly expressed in a latent viral replicative stage. The rest of open reading frames examined included mainly lytic-associated genes and showed no expression.
The spectrum of expressed viral genes is not the same as can be observed in Kaposi's sarcoma or multicentric Castleman's disease, suggesting that human herpesvirus-8 plays a different role in the pathogenesis of its associated diseases. These differences may be related to either cell-specific or immunologic host factors.
IL-6 Overproduction of IL-6
Am J Surg Pathol 1995;19:590–595
IL-6 promotes the proliferation of fibroblasts, and both IL-1 and IL-6 promote differentiation of B cells
The major cellular sources of IL-1 and IL-6 are monocytes and macrophages which are constant constituents of IMT
May be related to the overproduction of these cytokines, whether produced by the host cells, tumor cells, or both, since there is the presence of synchronous tumors and inflammatory diseases in our patients
CHARACTERIZATION GENERAL VARIANTS BREAST
Ann Diagn Pathol. 2005 Jun;9(3):123-9. Abstract quote
Three patients developed firm, mobile, nontender masses in their breasts. Two were discovered by the patients and one after mammography. Macroscopically, the nodules were firm, circumscribed, yellow on cut sections, and composed of interlacing cytologically bland spindle cells admixed with chronic inflammatory cells, the latter predominantly of lymphocytes and plasma cells.
Immunohistochemistry yielded strong smooth-muscle actin reactivity within the spindle cells; 2 lesions were negative for pankeratin, 1 was focally and weakly positive. No lesions were positive for anaplastic lymphoma kinase-1, desmin, S-100, CD34, CD21, or CD35. In each case, a diagnosis of inflammatory myofibroblastic tumor was made (aka, inflammatory pseudotumor). After conservative excision with apparently negative margins, there have been no recurrences, except in one patient who developed a recurrence after 3 months. The latter recurrence was managed successfully with a second excision.
We report these patients to emphasize the diagnostic features of inflammatory myofibroblastic tumor of the breast and discuss how they can be distinguished from other spindle-cell breast lesions with which they can be confused, especially spindle-cell carcinoma.
- Inflammatory Pseudotumor of the Breast in a Patient With a High Serum IgG4 Level: Histologic Similarity to Sclerosing Pancreatitis.
Zen Y, Kasahara Y, Horita K, Miyayama S, Miura S, Kitagawa S, Nakanuma Y.
From the Departments of *Pathology, daggerSurgery, and double daggerDiagnostic Radiology, Fukui Saiseikai Hospital, Fukui, Japan; and the section signDepartment of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
Am J Surg Pathol. 2005 Feb;29(2):275-278. Abstract quote
The association between IgG4 and inflammatory pseudotumor was first reported with regard to pancreatic pseudotumor, which is well known as sclerosing pancreatitis or autoimmune pancreatitis. In addition, there is increasing evidence that IgG4 is also involved in inflammatory pseudotumor of the extrapancreatic tissue.
In this report, we present a case of IgG4-related inflammatory pseudotumor of the breast. A 46-year-old woman presented with an induration in the left breast. Radiologic examination revealed an ill-circumscribed mass measuring 1.6 cm in diameter in the left breast. Breast cancer could not be ruled out radiologically, and excision biopsy was performed for a definite diagnosis.
Histologically, this nodule was composed of an irregular proliferation of stromal cells associated with severe lymphoplasmacytic infiltration, obliterative phlebitis, and eosinophils. No atypical feature regarding the stromal cells or lymphocytes was observed. Furthermore, many plasma cells within the lesion were immunohistochemically positive for IgG4, and the serum IgG4 concentration of this patient was elevated on postoperative examination.
This case suggests that inflammatory pseudotumor of the breast has a pathogenetic process similar to that of sclerosing pancreatitis. IgG4 might become a useful marker for inflammatory pseudotumor of the breast, and it might benefit from steroid therapy, as does sclerosing pancreatitis.
CENTRAL NERVOUS SYSTEM
Inflammatory pseudotumors of the central nervous system: Report of 3 cases and a literature review.
Hausler M, Schaade L, Ramaekers VT, Doenges M, Heimann G, Sellhaus B.
Department of Pediatrics; Institute of Medical Microbiology, Division of Virology; Department of Neuroradiology, and Institute of Neuropathology, University Hospital, RWTH Aachen, Germany.
Hum Pathol 2003 Mar;34(3):253-62 Abstract quote
Inflammatory pseudotumors (IPs), mostly benign lesions characterized by fibrotic ground tissue and polyclonal mononuclear infiltrate, may affect all organ systems. IPs originating in the central nervous system (IP-CNS) are very rare, and their distinct histopathologic features are poorly characterized. Three otherwise healthy patients (age 8, 15, and 17 years) presented with focal neurologic symptoms (seizures, n = 2; headaches, n = 1), corresponding to a left temporal, left occipital, and left frontal IP, respectively, extending from meningeal structures into brain tissue.
After resection, no recurrence was observed in patient 1 during 5 years of follow-up, whereas patient 2 developed a rapidly progressive local recurrence and a second intracerebral lesion despite antiviral, immunosuppressive, antibiotic, and radiation therapy. In patient 3, who also showed local recurrences, sequential histopathologic investigations revealed transformation to a semimalignant fibrohistiocytic tumor. In this patient, anaplastic lymphoma kinase (ALK) expression was also positive, whereas it was negative in patient 1. A detailed literature analysis confirmed that most IP-CNS arise from dural/meningeal structures (n = 34). Intraparenchymatous (n = 7), mixed intraparenchymatous/meningeal (n = 4), and intraventricular lesions (n = 7) or IP extending per continuitatem from intracerebral to extracerebral sites (n = 5) were rare. The recurrence rate was 40% within 2 years in general. It was increased after incomplete resection and in female patients (multivariate Cox regression model, P < 0.02).
Although rare, IP-CNS are important differential diagnoses among tumor-like intracranial lesions. Their potential risk of malignant transformation and high risk of recurrence necessitate close follow-up, especially when resection is incomplete. Prospective multicenter trials are needed to optimize classification and treatment of this rare inflammatory lesion.
Inflammatory myofibroblastic tumors (inflammatory pseudotumors) of the gastrointestinal tract: How closely are they related to inflammatory fibroid polyps?
Makhlouf HR, Sobin LH.
Division of Gastrointestinal Pathology, Department of Hepatic and Gastrointestinal Pathology, Armed Forces Institute of Pathology, Washington, DC.
Hum Pathol 2002 Mar;33(3):307-15 Abstract quote
Inflammatory myofibroblastic tumors (inflammatory pseudotumors) and inflammatory fibroid polyps of the gastrointestinal tract both feature prominent inflammatory infiltrates admixed with spindle-shaped fibroblasts/myofibroblasts set in a collagenous, fibrovascular, or myxoid stroma. Erroneously, some have considered inflammatory fibroid polyps to be intraluminal manifestations of inflammatory myofibroblastic tumors.
In this study, we have characterized the histopathology of inflammatory myofibroblastic tumors, tumors that have only rarely been reported in the gastrointestinal tract, and have focused on whether inflammatory myofibroblastic tumors and inflammatory fibroid polyps in the gastrointestinal tract are distinct or similar. Clinical, histopathologic, and immunohistochemical features of 38 inflammatory myofibroblastic tumors limited to the wall of the gastrointestinal tract were compared with those of 45 inflammatory fibroid polyps.
Compared to patients with inflammatory fibroid polyps, those with inflammatory myofibroblastic tumors were younger (mean age 41 years vs. 53 years); had larger tumors (mean 8 +/- 5.2 cm vs. 3.6 +/- 4.6 cm); presented with abdominal pain, fever, and weight loss more frequently and less frequently had bowel obstruction. Inflammatory fibroid polyps had more eosinophils and fibrosis and fewer lymphoid cell infiltrates than inflammatory myofibroblastic tumors. A regular vascular pattern was a feature of inflammatory fibroid polyps but not of inflammatory myofibroblastic tumors. Most (82%) inflammatory fibroid polyps were positive for CD34 versus none of the inflammatory myofibroblastic tumors. Smooth muscle actin was more frequently positive in inflammatory myofibroblastic tumors than in inflammatory fibroid polyps (86% versus 13%). Inflammatory myofibroblastic tumors were much less frequent and were more evenly distributed in the gastrointestinal tract than inflammatory fibroid polyps. Both appear to be benign processes. Inflammatory myofibroblastic tumors, but not inflammatory fibroid polyps, had a tendency to recur.
In conclusion, inflammatory myofibroblastic tumors of the gastrointestinal tract are extremely rare and differ clinically, histologically, and immunohistochemically from inflammatory fibroid polyps.
- Cardiac Inflammatory Myofibroblastic Tumor: A "Benign" Neoplasm That May Result in Syncope, Myocardial Infarction, and Sudden Death.
*CVPath Institute Inc, Gaithersburg, MD †The University of Maryland Medical School, Baltimore ‡The Armed Forces Institute of Pathology, Washington, DC.
- Am J Surg Pathol. 2007 Jul;31(7):1115-1122. Abstract quote
Cardiac tumors other than myxomas are rare. We report a series of 10 intracavitary polypoid myofibroblastic proliferations in children and young adults emphasizing gross, histologic, and clinical features. There were 6 females and 4 males, with a mean age of 10 years (range 5 wk to 21 y).
All lesions were endocardial-based, located in the right atrium (1), right ventricular inflow/tricuspid valve (1), right ventricular outflow (3), mitral valve (3), aortic valve/left coronary sinus (1), and left ventricular free wall (1).
Symptoms included shortness of breath or dyspnea (3), syncope (2), chest pain (1), transient ischemic attacks (1), and fever with myalgias (1). All tumors were surgical resections, except 1 tumor that resulted in sudden coronary death and that was diagnosed at autopsy, and 1 tumor that embolized into the coronary artery and was treated by cardiac transplant. Two tumors, present in the aortic and mitral valves, respectively, caused cardiac ischemia. The tumors were polypoid or filiform and histologically resembled inflammatory myofibroblastic tumors of extracardiac sites, with loose spindle cell growth with sparse inflammation. Although there were frequent collagen bundles interspersed among the tumor cells, there were no large areas of dense fibrosis. Surface fibrin was present on the polypoid projections in 7 cases. Symptoms resulted from prolapse into coronary ostia or embolization, but no patient developed metastasis. Long-term follow-up in 2 patients demonstrated no evidence of disease or recurrence. Although metastatic potential was not identified, these tumors may result in serious symptoms, including myocardial infarct, syncope, and sudden death.
These cardiac myofibroblastic tumors are readily distinguished from other endocardial-based cardiac tumors, including papillary fibroelastoma and myxoma, which may present clinically in the same manner.
Fibroma and inflammatory myofibroblastic tumor of the heart
Vincent Thomas de Montpréville, MD
Alain Serraf, MD
Hakim Aznag, MD
Nabila Nashashibi, MD
Claude Planché, MD
Elisabeth Dulmet, MD
Ann Diagn Pathol 2001;5:335-342 Abstract quote
Cardiac fibroma and inflammatory myofibroblastic tumor (IMT) of the heart are rare lesions occurring in young patients and having pathologic similarities.
We compared the morphologic and immunohistochemical features of seven cardiac fibromas, including one biopsied at birth and removed 4 years later, and two IMTs of the heart diagnosed at Marie Lannelongue Surgical Center (Le Plessis Robinson, France) between 1980 and 1999.
Cardiac fibromas occurred in five females and two males and were surgically biopsied (n = 2) or removed (n = 6) between the ages of 8 days to 31 years (mean 7 +/– 12 years). Inflammatory myofibroblastic tumors were removed in two male patients, aged 13 weeks and 1 year, both alive and well 9 months and 5 years after surgery, respectively. Fibromas were ventricular lesions measuring 3 to 10 cm (mean, 5.7 +/– 2.2 cm). They contained entrapped myocytes and wavy elastic fibers. Three cases contained calcifications. Spindle cells were monomorphic. Their nucleus had a thin chromatin without nucleolus. Mitoses and extramedullary hematopoiesis were only observed in fibromas from patients younger than 5 months (n = 5) while prominent collagen fibrosis was present in fibromas from patients older than 4 years (n = 3). Inflammatory myofibroblastic tumors were endocardial lesions measuring 2 and 2.5 cm. They were covered by fibrin. Spindle cells were larger than in fibromas. Their nucleus had obvious nucleoli. They were associated with numerous inflammatory cells in a variable amount of myxoid background. Occasional mitoses and foci of necrosis were present. Spindle cells in both fibromas and IMTs strongly expressed smooth-muscle actin and were negative for desmin, CD34, S-100 protein, and p53.
Our study shows that IMT must be considered in the differential diagnosis of cardiac fibroma especially in cases of inflammatory syndrome, location outside the ventricular myocardium, or multinodular lesions. Morphologic analysis permits the correct diagnosis, while immunochemistry shows a myofibroblastic differentiation in both lesions.
Inflammatory pseudotumor (myofibroblastic tumor) of the heart.
Li L, Cerilli LA, Wick MR.
Robert. E. Fechner Laboratory of Surgical Pathology, Department of Pathology, University of Virginia Health System, Charlottesville, VA.
Ann Diagn Pathol 2002 Apr;6(2):116-21 Abstract quote
Inflammatory pseudotumor (IPT) (also known as inflammatory myofibroblastic tumor) is an uncommon spindle cell lesion that was initially recognized in the lung and is now known to occur in virtually every major organ of the body. Its precise biological nature and clinical characteristics are still relatively uncertain.
We report the case of a 7-month-old girl who was found to have an IPT of the right atrium. The rarity of IPT in the heart poses a diagnostic difficulty for both pediatricians and pathologists because of the clinical and morphologic overlap with other intracardiac masses in children.
The differential diagnostic aspects of IPT of the heart are discussed and the literature on that lesion is reviewed.
Inflammatory myofibroblastic tumors of the kidney: a clinicopathologic and immunohistochemical study of 12 cases.
Kapusta LR, Weiss MA, Ramsay J, Lopez-Beltran A, Srigley JR.
Am J Surg Pathol 2003 May;27(5):658-66 Abstract quote
Inflammatory myofibroblastic tumor is a rare entity composed of spindle cells admixed with variable amounts of extracellular collagen, lymphocytes, and plasma cells.
In the genitourinary tract, inflammatory myofibroblastic tumor most commonly occurs in the bladder. Isolated case studies of inflammatory myofibroblastic tumor of the kidney, renal pelvis, and ureter have been previously reported.
Our series includes 12 cases of inflammatory myofibroblastic tumor occurring in the renal pelvis (six cases), renal parenchyma (four cases), and immediate perirenal soft tissue (two cases). Clinical presentation included flank pain (two patients), painless gross hematuria (one patient), and ureteropelvic junction stenosis with hydronephrosis (one patient). The remaining eight patients were asymptomatic. All patients underwent nephrectomy. The tumors were characterized by firm white tissue or had a myxoid "gelatinous" appearance.
Three histologic patterns were identified in the tumors, including a myxoid vascular pattern, a compact spindle cell pattern, and a hypocellular fibrous pattern. Immunohistochemical and electron microscopic studies supported a myofibroblastic proliferation. All cases were negative for anaplastic lymphoma kinase. Follow-up was available in eight cases and ranged from 1 to 17 years with no evidence of recurrence.
Based on this series, renal inflammatory myofibroblastic tumor is a proliferative lesion of myofibroblasts of uncertain pathogenesis with no identified potential for recurrence or metastases.
- IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung.
Zen Y, Kitagawa S, Minato H, Kurumaya H, Katayanagi K, Masuda S, Niwa H, Fujimura M, Nakanuma Y.
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan; Department of Pathology, Fukui Saiseikai Hospital, Fukui 918-8503, Japan.
Hum Pathol. 2005 Jul;36(7):710-7. Abstract quote
The association between IgG4 dysregulation and inflammatory pseudotumor (IPT) was first reported in sclerosing pancreatitis. Recently, we described IPTs of the liver and breast, into both of which many IgG4-positive plasma cells had infiltrated.
In this study, we examined the clinical and histological features of 9 cases of IPT (histologically corresponding to plasma cell granuloma) of the lung with an emphasis on IgG4-positive plasma cell infiltration. The lesions were characterized histologically by dense lymphoplasmacytic infiltrates intermixed with fibrosis and, in some cases, prominent eosinophilic infiltration, irregular narrowing of bronchioles entrapped in nodules, and an interstitial pneumonia pattern at the boundaries of nodules. Obliterative phlebitis was easily found in all cases, and 5 lesions also had obliterative arteritis.
Immunostaining revealed many IgG4-positive plasma cells diffusely distributed within nodules, and the ratios of IgG4-positive to other plasma cells were extraordinarily high. Of the 9 patients, 8 underwent surgical treatment and in 1 patient, lesion was diagnosed on transbronchial biopsy and effectively treated with corticosteroid. Two cases were associated with chronic sclerosing sialadenitis or lymphadenopathy, in which many IgG4-positive plasma cells were also identified by immunostaining.
The clinicopathologic similarities between IPT of the lung and sclerosing pancreatitis suggest that IgG4-related immunopathologic processes might be involved in the pathogenesis of the pulmonary lesions.
Inflammatory Pseudotumor of the Submandibular Gland Report of a Case Presenting With Autoimmune Disease-like Clinical Manifestations
Masaru Kojima, MD, Shigeo Nakamura, MD, Hideaki Itoh, MD, Taizan Suchi, MD, and Nobuhide Masawa, MD
From the Department of Pathology, Dokkyo University School of Medicine, Mibu, Japan (Drs Kojima and Masawa); the Department of Pathology and Genetics, Aichi Cancer Center Hospital, Nagoya, Japan (Drs Nakamura and Suchi); and the Department of Pathology and Clinical Laboratories, Maebashi Red Cross Hospital, Maebashi, Japan (Dr Itoh).
Arch Pathol Lab Med 2001;125:1095–1097 Abstract quote
We report a rare case of inflammatory pseudotumor arising in the submandibular gland, which presented with autoimmune disease–like clinical manifestations.
A 70-year-old Japanese man developed masses in both submandibular regions. Laboratory tests revealed polyclonal hypergammaglobulinemia, high titers of antinuclear antibody, and a positive thyroid test.
Histologically, the lesion was composed of multiple nodules separated by thick fibrous bands and contained a few atrophic lymphoid follicles and residual ductal structures. At higher magnification, the nodules contained numerous mature plasma cells mixed with myofibroblasts, lymphocytes, and histiocytes. Occasionally, the myofibroblasts were arranged in poorly formed fascicles and in a storiform pattern. Polymerase chain reaction analysis failed to demonstrated the rearrangement of the immunoglobulin heavy-chain gene. The patient was free of disease after 72 months follow-up. Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type arising from salivary glands occasionally showed prominent plasma cell differentiation.
The present case indicates that inflammatory pseudotumor should be added to the list of different diagnoses for mucosa-associated lymphoid tissue–type lymphoma of the salivary glands.
- Cutaneous inflammatory pseudotumor - a spectrum of various diseases?
Shabrawi-Caelen LE, Kerl K, Cerroni L, Soyer HP, Kerl H.
Department of Dermatology, Medical University of Graz, Graz, Austria.
J Cutan Pathol. 2004 Oct;31(9):605-11. Abstract quote
Background: Inflammatory pseudotumor (IPT) also known as inflammatory myofibroblastic tumor (IMT) or plasma cell granuloma (PCG) has been rarely reported in the skin.
Methods: We describe five patients with cutaneous IPT and present clinicopathologic features along with detailed immunohistochemical analysis including anaplastic lymphoma kinase (ALK)-1.
Results: The patients age ranged from 15 to 89 years with a median of 56 years. All patients presented with solitary, firm, papules and nodules. There was no evidence of constitutional symptoms, local recurrence, or lymph node involvement. Histopathological examination revealed two distinct patterns; one type (n = 3) displayed dense, lymphoplasmacytoid infiltrates containing lymphoplasmacytoid cells and plasma cells with occasional germinal centers and hyalinized collagen bundles but was devoid of a myofibroblastic component. It showed features of tumors previously described as cutaneous PCG. Although an infectious etiology, including Borrelia burgdorferi-specific DNA, could not be demonstrated, we observed many features that overlapped with those of fibrous nodules of acrodermatitis chronica atrophicans. The other pattern (n = 2) revealed spindled myofibroblasts focally arranged in a fascicular pattern, an admixed lymphoplasmacytoid infiltrate set in a background of thickened collagen bundles, findings akin to the conventional type of IMT. The cases with a myofibroblastic component (n = 2) did not show any evidence of ALK-1 reactivity.
Conclusions: We believe that the term cutaneous IPT subsumes lesions of diverse etiology. Tumors with detectable myofibroblasts represent true cases of IMT. Cutaneous PCG is a discrete disorder biologically distinct from conventional IMT representing a reaction pattern that is also found in disorders, such as spirochete-induced fibroid nodules and localized chronic fibrosing vasculitis.
SPLEEN Splenic Inflammatory Myofibroblastic Tumor (Inflammatory Pseudotumor): A Clinicopathologic and Immunophenotypic Study of 12 Cases
Arch Pathol Lab Med 125:379–385, 2001
Bland spindle cell proliferation in association with a variable mixed inflammatory component
There were 2 growth patterns:
Cellular spindle cell pattern
Hypocellular fibrous pattern
An immunohistochemical panel confirmed the myofibroblastic nature of the spindle cells
Spindle cells of 2 cases were immunoreactive for EBV latent membrane protein 1, whereas 6 of 10 cases were positive for EBV-encoded RNA using in situ hybridization
Uncommon lesions that can be distinguished from other conditions using a combination of clinical, histologic, and immunophenotypic findings
Epstein-Barr virus may play a role in the pathogenesis of splenic IMT, and there may be an association of splenic IMT with concomitant disease or malignancy
Most splenic IMTs have an excellent long-term prognosis
Splenic Inflammatory Myofibroblastic Tumor (Inflammatory Pseudotumor): A Clinicopathologic and Immunophenotypic Study of 12 Cases
Arch Pathol Lab Med 125:379–385, 2001
8 women and 3 men, ranging from 19 to 77 years of age (mean, 53 years; median, 60 years)
Patients generally presented with:
Abdominal pain (n = 5) and fever (n = 4)
Associated lesions included:
Renal cell carcinoma (n = 2)
Colonic adenocarcinoma (n = 1)
Cholecystitis (n = 1)
Follow-up was available for 8 patients; 6 were alive with no evidence of recurrence and 2 were dead of other causes
Uncommon lesions that can be distinguished from other conditions using a combination of clinical, histologic, and immunophenotypic findings
Epstein-Barr virus may play a role in the pathogenesis of splenic IMT, and there may be an association of splenic IMT with concomitant disease or malignancy
Most splenic IMTs have an excellent long-term prognosis
Inflammatory pseudotumor of lymph node and spleen: An entity biologically distinct from inflammatory myofibroblastic tumor
Jeffery L. Kutok, MD, PhD
Geraldine S. Pinkus, MD
David M. Dorfman, MD, PhD
Christopher D.M. Fletcher, MD, FRCPath
Hum Pathol 2002;32:1382-1387. Abstract quote
Inflammatory pseudotumors (IPTs) of the lymph node and spleen are an uncommon, benign cause of lymphadenopathy and/or splenomegaly that often bear striking clinicopathologic similarities to the inflammatory myofibroblastic tumors (IMTs) found in soft tissues. These tumors have classically been grouped together under the umbrella category of “inflammatory pseudotumor.” Recent evidence shows that IMTs are in fact neoplastic processes that often harbor balanced chromosomal translocations involving the ALK kinase gene. These translocations result in expression of ALK kinase in IMTs as assessed by immunohistochemical studies. However, the relationship between IMT and IPT of the lymph node and spleen is uncertain.
To determine if ALK tyrosine kinase expression is also present in IPT, 13 cases of IPT (9 involving lymph nodes, 4 splenic lesions) were examined for the presence of ALK tyrosine kinase by immunohistochemical staining on paraffin-embedded tissue. In addition, in situ hybridization studies for Epstein-Barr virus–encoded RNAs (EBER) and immunoperoxidase studies for human herpesvirus-8 (HHV8)–specific proteins were performed. All cases had clinical, morphologic, and immunophenotypic findings typical of IPT and had varying proportions of fibroblastic and inflammatory components. Age ranged from 11 to 75 (median, 40) years; 8 subjects were male, and 5 were female. None of the cases (0 of 13) had positive staining for ALK kinase or HHV8, and in 1 a lymph node (1 of 13) was focally positive for EBV (EBER) by in situ hybridization.
The absence of ALK kinase as detected by immunohistochemical studies in IPT of the lymph node and spleen suggests that this entity is biologically distinct from the histologically similar IMT.
- Inflammatory Myofibroblastic Tumors of the Urinary Tract: A Clinicopathologic Study of 46 Cases, Including a Malignant Example Inflammatory Fibrosarcoma and a Subset Associated With High-grade Urothelial Carcinoma.
- Montgomery EA,
- Shuster DD,
- Burkart AL,
- Esteban JM,
- Sgrignoli A,
- Elwood L,
- Vaughn DJ,
- Griffin CA,
- Epstein JI.
Department of Pathology, Johns Hopkins Hospital, Baltimore, MD 21231.
- Am J Surg Pathol. 2006 Dec;30(12):1502-12. Abstract quote
Inflammatory myofibroblastic tumor (IMT) of the urinary tract, also termed postoperative spindle cell nodule, inflammatory pseudotumor, and pseudosarcomatous fibromyxoid tumor, is rare and in the past was believed to reflect diverse entities.
We reviewed a series of 46 IMTs arising in the ureter, bladder, and prostate, derived primarily from a large consultation practice. There were 30 male and 16 females aged 3 to 89 years (mean 53.6). Lesions were 1.2 to 12 cm (mean 4.2). There was a history of recent prior instrumentation in 8 cases. Morphology was similar to that previously described for IMT occurring in this region, with the exception of 1 case that focally appeared sarcomatous. Polypoid cystitis coexisted in 5 patients (11%). Mitoses were typically scant (0 to 20/10 hpf, mean 1). Necrosis was seen in 14 (30%) cases. Invasion of the muscularis propria was documented in 19 (41%). By immunohistochemistry (IHC), lesions at least focally expressed anaplastic lymphoma kinase (ALK) (20/35, 57%), AE1/3 (25/34, 73%), CAM5.2 (10/15, 67%), CK18 (6/6, 100%), actin (23/25, 92%), desmin (15/19, 79%), calponin (6/7, 86%), caldesmon (4/7, 57%, rare cells), p53 (10/13, 77%), and most lacked S100 (0/14), CD34 (0/13), CD117 (2/13, 15%), CD21 (0/5), and CD23 (0/3). ALK gene alterations were detected by fluorescence in situ hybridization (FISH) in 13/18 (72%) tested cases, including 2 with prior instrumentation; 13/18 (72%) showed agreement between FISH ALK results and ALK protein results by IHC.
Most bladder IMTs were managed locally, but partial cystectomy was performed as the initial management in 7 cases and cystectomy in 1 (1 IMT was initially misinterpreted as carcinoma, 1 IMT was found incidentally as a separate lesion in a cystectomy specimen performed for urothelial carcinoma). Follow-up was available in 32 cases (range 3 to 120 mo; mean 33; median 24). There were 10 patients with recurrences (2 with 2 recurrences).
Recurrences were unassociated with muscle invasion or with ALK alterations. In 2 cases, tumors of the urinary tract (TURs) showing IMT preceded (1 and 2 mo, respectively) TURs showing sarcomatoid carcinoma with high-grade invasive urothelial carcinoma accompanied with separate fragments of IMT. Even on re-review the IMT in these 2 cases were morphologically indistinguishable from other cases of IMT, with FISH demonstrating ALK alterations in the IMT areas in one of them. Both these patients died of their carcinomas. Lastly, there was 1 tumor with many morphological features of IMT and an ALK rearrangement, yet overtly sarcomatous. This case arose postirradiation for prostate cancer 4 years before the development of the lesion, with tumor recurrence at 4 months and death from intra-abdominal metastatic disease at 9 months.
In summary, urinary tract IMTs are rare and share many features with counterparts in other sites, displaying similar morphology and immunogenotypic features whether de novo or postinstrumentation. Typical IMTs can be locally aggressive, sometimes requiring radical surgical resection, but none of our typical cases metastasized, although they can rarely arise contemporaneously with sarcomatoid urothelial carcinomas. For these reasons, close follow-up is warranted.
Am J Surg Pathol. 2006 Jul;30(7):787-794. Abstract quote
Inflammatory pseudotumor or pseudosarcomatous fibromyxoid tumor and postoperative spindle cell nodule of the bladder are unusual lesions of uncertain pathogenesis which share overlapping, if not identical, histologic features.
We present our experience with 42 cases, the largest series to date, to study the etio-pathogenesis, histologic features, biologic behavior and relationship to "inflammatory myofibroblastic tumor" of childhood. Patients ranged in age from 7 to 77 years (mean 47 y) and males predominated (3.2:1). Most patients presented with hematuria (31/42).
Common associations were smoking (10/30) and previous instrumentation or surgery (9/42). The clinicopathologic features of patients having or not having prior instrumentation were identical. Grossly the lesions were polypoid or nodular and involved any portion of bladder wall, most commonly the dome (9/27) and measured 1 to 10 cm (mean 4 cm). They were composed of spindled and stellate cells arranged in a myxoid background with numerous inflammatory cells. Myxoid hypocellular areas were more pronounced near the mucosal surface with greater cellularity and a fascicular arrangement in the deep aspect of the lesion.
"Atypical" features included mitotic activity (0 to 20/10 HPF; mean 2/10 HPF; median 1/10 HPF; none atypical), necrosis (22/42), and extension into muscularis propria (28/32) or perivesicular fat (3/8). Lesions were positive for cytokeratin (31/33), SMA (23/34), desmin (21/35), and Alk-1 protein (12/26). FISH confirmed the Alk-1 translocation in 4/6 cases. Treatment included transurethral resection (30/42), partial cystectomy (9/42), and total cystectomy (3/42). Initial diagnostic error resulted in radiotherapy and chemotherapy in 3 patients. Follow-up was available in 28 patients. (range 3to 93 mo; median 25 mo). Three patients developed recurrences, but none had metastases. Because the clinicopathologic features of lesions associated with and without instrumentation were similar and inseparable, we believe they are essentially the same entity, and propose the term pseudosarcomatous myofibroblastic proliferation. The preponderance of evidence which includes the extravesical growth, local recurrence, and Alk-1 gene translocation in some cases suggests perhaps a neoplastic process with limited growth potential.
Even in the face of atypical histologic features (muscle invasion and necrosis) the prognosis is excellent. Despite the Alk-1 gene translocation, there continues to be sufficient evidence for regarding these as distinct from the so-called inflammatory myofibroblastic tumor of childhood.
- ALK-1 Expression in Inflammatory Myofibroblastic Tumor of the Urinary Bladder.
Tsuzuki T, Magi-Galluzzi C, Epstein JI.
From the *Department of Pathology, Johns Hopkins Hospital, Baltimore, MD; daggerDepartment of Pathology, Nagoya Daini Red Cross Hospital, Nagoya, Japan; and double daggerDepartment of Pathology, Cleveland Clinic Foundation, Cleveland, OH.
Am J Surg Pathol. 2004 Dec;28(12):1609-1614. Abstract quote
Inflammatory myofibroblastic tumor (IMT) of the bladder is an uncommon myofibroblastic spindle cell proliferation. Because of its cytologic features and infiltrative nature, it may be difficult to distinguish histologically from sarcomatous proliferations such as sarcomatoid urothelial carcinoma, leiomyosarcoma, and embryonal rhabdomyosarcoma. Recently, anaplastic lymphoma kinase (ALK) gene translocations or ALK protein expression in IMT has been reported, especially in patients of relatively young ages. However, there are only a few reports mentioning IMT of the bladder.
We sought to determine the frequency of ALK expression among IMTs of the urinary bladder. We examined 16 cases of IMTof the bladder in 14 patients to elucidate the incidence of ALK-1 expression by immunohistochemistry and its diagnostic usefulness. The age of patients with IMT ranged from 18 to 76 years, with an average age of 42.8 years. The tumors from 10 of 14 patients (12 of 16 cases) were positive for ALK-1. ALK-1-positive cases ranged in age from 18 to 73 years (mean, 39.2 years; median, 38 years) and ALK-1-negative cases from 41 to 76 years (mean, 41.5 years; median, 44.5 years). Two locally recurrent cases were positive for ALK-1 in both the primary and recurrent lesion. ALK-1 immunostaining was detected only in the cytoplasm, with granular or subplasmalemmal linear features, suggesting ALK gene translocation. ALK-1 immunostaining was also performed in 8 sarcomatoid urothelial carcinomas, 5 genitourinary leiomyosarcomas, and 2 stromal tumors of uncertain malignant potential of the prostate, all of which were negative.
These results support that ALK-1 immunostaining is useful to differentiate IMT from other malignant spindle cell neoplasms of the bladder. There were no histologic differences between ALK-1 positive and negative IMTs.
Pseudosarcomatous Myofibroblastic Tumor and Myosarcoma of the Urogenital Tract Immunohistochemical Characteristics and Differential Diagnosis
Kazuo Watanabe, MD, Keiich Baba, MD, Atsuko Saito, MD, Nobuo Hoshi, MD, and Toshimitsu Suzuki, MD
From the Pathology (Drs Watanabe, Hoshi, and Suzuki) and Urology (Dr Baba) Divisions, Fukushima Medical University School of Medicine Hospital, Fukushima City, Japan, and the Pathology Division, Jusendo General Hospital, Koriyama City, Japan (Dr Saito).
Arch Pathol Lab Med 2001;125:1070–1073. Abstract quote
Objective. —Pseudosarcomatous myofibroblastic tumors (PMTs) of the urogenital tract are rare but distinctive lesions. Despite their benign behavior, they are frequently misinterpreted as leiomyosarcomas and rhabdomyosarcomas in preoperative biopsies and even in resected specimens because of their atypical spindle-cell features. Precise diagnosis of PMTs is important to avoid unnecessary radical therapy. We analyzed urogenital myoid tumors to clarify which of their characteristics are useful for the differential diagnosis.
Methods. —We evaluated 7 urogenital myoid tumors consisting of 3 PMTs, 2 leiomyosarcomas, and 2 rhabdomyosarcomas. We studied the expression of various immunohistochemical muscle-cell markers including desmin, muscle-specific actin, -smooth muscle actin, high-molecular-weight caldesmon, and myogenin.
Results.—Desmin, muscle-specific actin, and -smooth muscle actin were noted variably in all tumor types, whereas high-molecular-weight caldesmon was expressed only in leiomyosarcomas, and myogenin was expressed only in rhabdomyosarcomas.
Conclusion.—High-molecular-weight caldesmon and myogenin are useful for differentiating urogenital PMTs from myosarcomas.
- Inflammatory Myofibroblastic Tumor of the Uterus: A Clinicopathologic Study of 6 Cases Emphasizing Distinction From Aggressive Mesenchymal Tumors.
Rabban JT, Zaloudek CJ, Shekitka KM, Tavassoli FA.
From the *Department of Anatomic Pathology, University of California, San Francisco, CA; daggerDepartment of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington, DC; and double daggerDepartment of Pathology, Yale University School of Medicine, New Haven, CT.
Am J Surg Pathol. 2005 Oct;29(10):1348-1355. Abstract quote
Inflammatory myofibroblastic tumor (IMT) is an indolent spindle cell proliferation that can histologically resemble various malignant mesenchymal neoplasms; however, it generally behaves as a benign or locally recurrent tumor. Most IMTs involve the lung, mesentery, omentum, or retroperitoneum.
We report the clinical and pathologic features of six IMTs of the uterus, one of which was included in a previous report, and emphasize the histologic and immunohistochemical features that distinguish IMTs from uterine spindle cell neoplasms that require aggressive treatment. Recently, translocations of the anaplastic lymphoma kinase (ALK) gene and immunohistochemical expression of ALK have been reported in IMTs of various anatomic sites. We compared ALK expression in uterine IMTs with that in uterine mesenchymal neoplasms with which it may be confused. Patients with IMT were between 6 and 46 years of age. None had a history of abdominal surgery; three were multiparous. The IMTs ranged from 1 to 12 cm in maximum dimension. Three grew as polypoid masses that arose in the lower uterine segment, and two of these prolapsed through the cervical os. The three other tumors grew as bulky myometrial masses with focally irregular borders and infiltrated the endometrium, parametrium, or cervical stroma.
There were three main microscopic patterns: a hypocellular pattern, a fascicular pattern, and a hyalinized pattern. A lymphoplasmacytic infiltrate was present in all of the tumors, and most had a myxoid background. Mitotic activity ranged from 0 to 2 mitotic figures per 10 high power fields (HPF) except in one tumor that focally had up to 8 mitotic figures per 10 HPF. No nuclear atypia or necrosis was present. Immunohistochemical expression of ALK was present in a cytoplasmic pattern in all IMTs tested. No ALK expression was identified in uterine leiomyoma (n = 7), leiomyosarcoma (n = 6), carcinosarcoma (n = 4), endometrial stromal sarcoma (n = 4), or normal uterine tissues.
Follow-up ranging from 1.5 years to 5 years in 4 patients with uterine IMTs revealed no recurrence or metastasis. IMTs should be differentiated from aggressive uterine mesenchymal tumors because they can be treated conservatively and have a more favorable prognosis. ALK expression appears to be of diagnostic value in conjunction with other immunohistochemical stains.
HISTOLOGICAL TYPES CHARACTERIZATION General
Three main histologic patterns:
Desmoid or scar tissue-type
CHARACTERIZATION Immunoperoxidase ALK Anaplastic lymphoma kinase (ALK 1) staining and molecular analysis in inflammatory myofibroblastic tumours of the bladder: a preliminary clinicopathological study of nine cases and review of the literature.
Freeman A, Geddes N, Munson P, Joseph J, Ramani P, Sandison A, Fisher C, Parkinson MC.
Department of Histopathology, University College Hospital, London.
Mod Pathol. 2004 Jul;17(7):765-71. Abstract quote
Inflammatory myofibroblastic tumours (IMFT) may arise at any anatomical site, including lung, soft tissues, retroperitoneum and bladder. Although morphologically similar, these lesions encompass a spectrum of entities with differing aetiology, ranging from reactive/regenerative proliferations to low-grade neoplasms with a risk of local recurrence, but no significant metastatic potential.
Vesical IMFT usually presents as a polypoid mass with a pale firm cut surface and can be of considerable size, mimicking a malignant tumour clinically and radiologically. Its good outcome, however, warrants conservative surgical excision, emphasising the importance of identification and distinction from malignant tumours of the bladder that may require more radical surgery and/or adjuvant therapy.
We conducted a preliminary retrospective, comparative immunocytochemical study of 20 bladder tumours, including nine IMFTs, five spindle cell (sarcomatoid) carcinomas, two rhabdomyosarcomas, two leiomyosarcomas and two neurofibromas. The results confirmed IMFT positivity for smooth muscle actin, desmin and cytokeratin in 78-89% cases, resulting in potential confusion with sarcomatoid carcinoma or leiomyosarcoma. In contrast, cytoplasmic anaplastic lymphoma kinase (ALK 1) staining was present in eight IMFT (89%), but was not seen in any other lesion examined. The ALK 1 staining was confirmed by fluorescence in situ hybridisation, with translocation of the ALK gene present in 15-60% tumour cells in four of six IMFT examined, but not in four cases of sarcomatoid carcinoma or three of leiomyosarcoma.
In conclusion, ALK 1 staining may be of value in the distinction of vesical IMFT from morphologically similar entities, and often reflects ALK gene translocations in these lesions.
Anaplastic Lymphoma Kinase Expression in Inflammatory Pseudotumors
John K. C. Chan, etal.
Am J Surg Pathol 2001;25:761-768 Abstract quote
Anaplastic lymphoma kinase (ALK), a hallmark of anaplastic large cell lymphoma, has recently been implicated in the genesis of some inflammatory pseudotumors (inflammatory myofibroblastic tumors) in children and young adults. The aim of this study was to determine the frequency of its expression among inflammatory pseudotumors, and to characterize the clinicopathologic features of the positive cases.
Sixty-one cases of inflammatory pseudotumors were retrieved from the surgical pathology archives and consultation files. Paraffin sections were immunostained with the antibody ALK1. The patients ranged in age from 0.5 to 79 years (median age, 50 years), with 10 patients (16.4%) younger than 20 years.
Five cases (8.2%) were ALK+, including two of six urogenital inflammatory myofibroblastic tumors, none of eight pulmonary inflammatory pseudotumors, three (one adrenal, one small bowel, one liver) of 31 extrapulmonary inflammatory pseudotumors, none of nine hepatic/splenic inflammatory pseudotumors expressing follicular dendritic cell markers and harboring Epstein–Barr virus, and none of seven inflammatory pseudotumors of the lymph node.
When only those patients 40 years or younger were considered, the ALK positivity rate became 21.7% (five of 23). All five ALK+ cases occurred in young patients aged 0.5 to 37 years, who were alive and well at 3.5 to 17 years. The tumors exhibited a spectrum of histologic features typical of inflammatory pseudotumors/myofibroblastic tumors, but there was at least focal nuclear atypia. Immunostaining for ALK produced fibrillary or granular cytoplasmic staining in the neoplastic cells, sometimes with cell membrane accentuation.
This study confirms that ALK is implicated in a proportion of inflammatory pseudotumors, and is generally associated with a favorable outcome. The results also support the heterogeneity of inflammatory pseudotumors, with the follicular dendritic cell/Epstein–Barr virus-positive cases and those occurring in lymph nodes representing different biologic entities.
ALK1 and p80 Expression and Chromosomal Rearrangements Involving 2p23 in Inflammatory Myofibroblastic Tumor
Cheryl M. Coffin, M.D., Ankita Patel, Ph.D., Sherrie Perkins, M.D., Kojo S.J. Elenitoba-Johnson, M.D., Elizabeth Perlman, M.D. and Constance A. Griffin, M.D.
University of Utah (CMC, SP, KSJE-J), Salt Lake City, Utah; and Johns Hopkins Medical Institutions (AP, EP, CAG), Baltimore, Maryland
Mod Pathol 2001;14:569-576 Abstract quote
Background: Inflammatory myofibroblastic tumor (IMT) is an uncommon tumor of extrapulmonary and pulmonary tissues with an unpredictable clinical course, occasional recurrences, and rare malignant transformation. Clonal abnormalities with rearrangements of chromosome of 2p23 and the ALK gene have been reported in a few cases. The purpose of this study is to investigate whether these are consistent abnormalities among IMTs or represent a distinct subset.
Design: Formalin-fixed, paraffin-embedded archival tissue sections from 47 IMTs in 40 patients were immunostained with monoclonal antibodies against ALK and p80. Fluorescence in situ hybridization for ALK rearrangements was done on 22 IMTs from 19 patients. Findings were correlated with clinical features and outcome.
Results: ALK positivity was observed in 17 of 47 IMTs (36%) and p80 positivity in 16 of 47 IMTs (34%). Fluorescence in situ hybridization showed ALK rearrangements in nine cases (47%), aneuploidy in three cases (16%), and no rearrangement in seven cases (37%). IMTs with ALK abnormalities by immunohistochemistry and/or fluorescence in situ hybridization originated in the abdomen/pelvis/retroperitoneum, chest, and extremities. The mean age was 6.6 years, with a male/female ratio of 1.3. 64% of patients had no evidence of disease at last follow-up, 45% had one or more recurrences, and 18% displayed histologic evidence of malignant transformation. The IMTs without ALK abnormalities occurred in older children, were more frequent in females, and had fewer recurrences. However, in this group of 40 patients, the differences between the groups with and without ALK abnormalities did not have statistical significance. Aneuploidy without ALK abnormalities was associated with malignant transformation in three of five cases.
Conclusions: Abnormalities of ALK and p80 and evidence of chromosomal rearrangements of 2p23 occur in a significant proportion of IMTs. These changes are most frequent in abdominal and pulmonary IMTs in the first decade of life and are associated with a higher frequency of recurrence. These findings confirm the neoplastic nature of a subset IMT with ALK abnormalities and suggest that aneuploid IMT is a subset with more aggressive clinical behavior.
Anaplastic Lymphoma Kinase (ALK) Expression in the Inflammatory Myofibroblastic Tumor A Comparative Immunohistochemical Study
James R. Cook, M.D. , Ph.D. ; Louis P. Dehner, M.D. ; Margaret H. Collins, M.D. ; Zhigui Ma, M.D. ; Stephan W. Morris, M.D. ; Cheryl M. Coffin, M.D. ; D. Ashley Hill, M.D.
From the Lauren V. Ackerman Division of Surgical Pathology (J.R.C., L.P.D.), Washington University School of Medicine, St. Louis, Missouri; Department of Pathology (M.H.C.), University of Cincinnati Medical Center, Cincinnati, Ohio; Department of Pathology (Z.M., S.W.M., D.A.H.), St. Jude Children's Research Hospital, Memphis, Tennessee; and the Department of Pathology (C.M.C.), University of Utah School of Medicine, Salt Lake City, Utah, U.S.A.
Am J Surg Pathol 2001;25:1364-1371 Abstract quote
Inflammatory myofibroblastic tumor (IMT) is an uncommon mesenchymal neoplasm with a variable histologic appearance that may mimic other spindle cell processes, particularly nodular fasciitis, desmoid tumor, and in intra-abdominal locations, gastrointestinal stromal tumor. Recently, gene fusions involving ALK at chromosome 2p23 have been described in IMTs. The resultant ALK protein overexpression in the myofibroblastic component of these tumors is detectable by immunohistochemistry.
We examined 73 IMTs, 20 cases of nodular fasciitis, 15 desmoid fibromatoses, and 15 gastrointestinal stromal tumors by immunohistochemistry using ALK-11, a rabbit polyclonal antibody that recognizes the C-terminus of the protein. ALK positivity was detected in 44 of 73 (60%) IMTs. All cases of nodular fasciitis, desmoid fibromatosis, and gastrointestinal stromal tumors were ALK negative (p < 0.001).
These findings demonstrate that ALK positivity is common in IMTs, and immunohistochemistry using anti-ALK antibodies can be helpful in the differential diagnosis of these neoplasms. In addition, anti-ALK staining seems to correlate with those IMTs that have the typical tri-patterned histologic appearance and clinical presentation, providing additional support to the premise that IMT is a distinctive clinicopathologic entity within the broad category of inflammatory pseudotumors.
Expression of ALK1 and p80 in Inflammatory Myofibroblastic Tumor and Its Mesenchymal Mimics: A Study of 135 Cases.
Cessna MH, Zhou H, Sanger WG, Perkins SL, Tripp S, Pickering D, Daines C, Coffin CM.
Department of Pathology, Primary Children's Medical Center and University of Utah School of Medicine, Salt Lake City, Utah (MHC, HZ, SLP, ST, CD, CMC).
Mod Pathol 2002 Sep;15(9):931-8 Abstract quote
Abnormalities of chromosome 2p23 with expression of ALK1 and p80 occur in both inflammatory myofibroblastic tumor (IMT) and anaplastic large cell lymphoma. This immunohistochemical study investigates whether the ALK family of neoplasms includes fibroblastic-myofibroblastic, myogenic, and spindle cell tumors.
Formalin-fixed paraffin-embedded archival tissues from 10 IMTs and 125 other soft tissue tumors were stained for ALK1 and p80 with standard immunohistochemistry. ALK1 and/or p80 reactivity was observed in a cytoplasmic pattern in IMT (4/10; 40%), malignant peripheral nerve sheath tumor (4/10; 40%), rhabdomyosarcoma (6/31; 19%), leiomyosarcoma (1/10; 10%), and malignant fibrous histiocytoma (1/11; 9%). No staining was observed in nodular fasciitis, desmoid, infantile myofibromatosis, infantile fibrosarcoma, synovial sarcoma, leiomyoma, or myofibrosarcoma. Alveolar rhabdomyosarcomas (4/16; 25%) displayed a distinctive dot-like cytoplasmic positivity. No cases displayed nuclear reactivity. Fluorescent in situ hybridization on 12 of the positive cases revealed a combination of abnormalities including ALK break-apart signals, nucleophosmin (NPM)/ALK fusions, or extra copies of 2p23. This study demonstrates that in addition to IMT, abnormalities of ALK1 and p80 expression with a variety of structural chromosomal changes are found in several sarcomas, especially rhabdomyosarcoma and malignant peripheral nerve sheath tumor. Although immunoreactivity in non-IMTs cannot distinguish between structural abnormalities involving 2p23 or additional copies of 2p23, it supports the concept of ALK involvement in a larger group of neoplasms, some of which have other documented clonal abnormalities.
In IMT, immunohistochemistry for ALK1 and p80 is useful as an indicator of a 2p23 abnormality, but it must be interpreted in the context of histologic and other clinicopathologic data if used as an adjunct to differential diagnosis.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES CALCIFYING FIBROUS PSEUDOTUMOR
Calcifying Fibrous Pseudotumor versus Inflammatory Myofibroblastic Tumor: A Histological and Immunohistochemical Comparison
Kalisha A. Hill, M.D., Frank Gonzalez-Crussi, M.D. and Pauline M. Chou, M.D.
Department of Surgical PathologyChildren’s Memorial Hospital, Northwestern University, Chicago, Illinois
Mod Pathol 2001;14:784-790 Abstract quote
Calcifying fibrous pseudotumor (CFP), a recently described lesion, is characterized by a predominantly lymphoplasmacytic infiltrate with abundant hyalinized collagen and psammomatous or dystrophic calcifications. The cause and pathogenesis are unclear, but it has been postulated that CFP may represent a sclerosing end stage of inflammatory myofibroblastic tumor (IMT).
We compared the histological and immunohistochemical profiles of seven cases diagnosed as CFP and seven as IMT.
Histologically, the CFP demonstrated varying degrees of calcifications in addition to fibroblastic proliferation admixed with inflammatory cells composed of lymphocytes, eosinophils, and mast cells. The IMTs rarely contain calcifications and had a myofibroblastic proliferation varying from hyalinized acellular collagen to florid fibroblastic proliferations simulating sarcoma. The inflammatory component was composed primarily of plasma cells and lymphocytes, sometimes arranged as lymphoid aggregates with germinal centers. All CFP cases were diffusely positive for factor XIIIa and negative for smooth muscle actin, muscle-specific actin, and CD34. All IMTs demonstrated diffuse positivity for actin, variable positivity for CD34, and focal positivity for Factor XIIIa.
This study demonstrates certain distinct histologic, immunohistochemical, and electron microscopic features between IMTs and CFPs.
INFLAMMATORY PSEUDOTUMOR-LIKE FOLLICULAR DENDRITIC CELL TUMOR
Inflammatory Pseudotumor-Like Follicular Dendritic Cell Tumor A Distinctive Low-Grade Malignant Intra-abdominal Neoplasm With Consistent Epstein–Barr Virus Association
Wah Cheuk, etal.
Am J Surg Pathol 2001;25:721-731 Abstract quote
Follicular dendritic cell (FDC) tumors are uncommon neoplasms that can involve lymph nodes or extranodal sites. They can exhibit a broad spectrum of histologic appearances and behavior, but the intra-abdominal ones usually pursue an aggressive course.
The purpose of this study was to characterize a distinctive variant of FDC tumor morphologically mimicking inflammatory pseudotumor through analysis of the clinicopathologic features of 11 cases. The patients included 10 women and one man (age range, 19–61 years; median age, 40 years) who presented with abdominal discomfort or pain. Six patients had systemic symptoms such as marked weight loss, fever, or malaise. All tumors occurred in intra-abdominal sites: liver (n = 7), spleen (n = 3), and peripancreatic region (n = 1). Of the nine patients with follow-up data, six were alive and well, one developed recurrence at 9 years, and two had repeated recurrences over many years.
Grossly, the tumors were usually solitary and fleshy, punctuated by areas of hemorrhage and necrosis. Histologically, in a background of abundant lymphocytes and plasma cells were dispersed spindle or ovoid cells with vesicular nuclei and distinct nucleoli. The degree of nuclear atypia was variable, and some nuclei could be grotesque or resemble Reed–Sternberg cells. Focally, spindle cell fascicles could be formed. The atypical cells were immunoreactive for FDC markers such as CD21/CD35, CD23, and CNA.42. In situ hybridization for Epstein–Barr virus (EBV)-encoded RNA was positive in all cases, remarkably highlighting the spindle cells and their atypia. EBV–latent membrane protein-1 was expressed commonly, albeit often focally and weakly.
Therefore, inflammatory pseudotumor-like FDC tumor represents a distinctive variant of FDC tumor that differs from conventional FDC tumor in the following aspects: marked female predominance; selective localization in intra-abdominal sites, especially the liver and spleen; frequent presence of systemic symptoms; indolent behavior despite an intra-abdominal location; dispersed distribution of tumor cells and prominent lymphoplasmacytic infiltration; and consistent association with EBV.
PRIMITIVE MYXOID MESENCHYMAL TUMOR OF INFANCY
- Primitive Myxoid Mesenchymal Tumor of Infancy: A Clinicopathologic Report of 6 Cases.
Alaggio R, Ninfo V, Rosolen A, Coffin CM.
*Department of Oncology and Surgery, Section of Pathology daggerDepartment of Pediatrics, University of Padova, Padova, Italy double daggerDepartment of Pathology, Primary Children's Medical Center and University of Utah School of Medicine, Salt Lake City, UT.
Am J Surg Pathol. 2006 Mar;30(3):388-394. Abstract quote
Soft tissue sarcomas in the first year of life are rare, and the most common sarcomas in infancy are embryonal rhabdomyosarcoma, Ewing sarcoma/primitive neuroectodermal tumor, congenital infantile fibrosarcoma, and primitive sarcomas such as undifferentiated sarcoma.
In this study, we report 6 cases of a primitive myxoid mesenchymal tumor of infancy (PMMTI), which previously may have been included under the diagnostic categories of congenital-infantile fibrosarcoma or infantile fibromatosis. PMMTI occurred in 6 infants, 3 of whom had a congenital presentation of a soft tissue mass. All patients were otherwise healthy. The tumors occurred on the trunk, extremities, and head and neck. Grossly, the tumors were nonencapsulated and had a multinodular appearance with focal infiltrative growth, a white fleshy cut surface, and a tumor diameter ranging from 2 to 15 cm.
Histologically, a diffuse growth of primitive spindle, polygonal, and round cells occurred in a myxoid background. The tumor cells were arranged in a vaguely nodular pattern with peripheral collagenized stroma, higher cellularity at the periphery, and a delicate vascular network in the background.
Immunohistochemically, the tumors displayed diffuse reactivity for vimentin and no reactivity for smooth muscle actin, muscle specific actin, desmin, S-100 protein, or myogenin. Electron microscopy documented a poorly differentiated fibroblastic proliferation. Four cases tested negative for the ETV6-NTRK3 gene fusion by RT-PCR. One tumor had a complex karyotypic abnormality with rearrangements involving chromosomes Y, 9, and 3. Three patients had recurrences or metastasis treated with a combination of surgery and chemotherapy. One patient is alive with persistent locally aggressive disease, 2 are alive with no evidence of recurrence, 1 had a recurrence treated surgically without further follow-up information, 1 patient died with persistent tumor and sepsis 6 weeks after diagnosis, and 1 patient was lost to follow-up.
The morphologic appearance combined with the ultrastructural features and absence of the typical gene rearrangement of congenital-infantile fibrosarcoma are unique, and we propose that PMMTI represents a new category of pediatric fibroblastic-myofibroblastic tumor.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS METASTASIS
Inflammatory myofibroblastic tumor with bone marrow involvement. A case report and review of the literature.
Hagenstad CT, Kilpatrick SE, Pettenati MJ, Savage PD.
Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Arch Pathol Lab Med. 2003 Jul;127(7):865-7. Abstract quote
Inflammatory myofibroblastic tumor, also referred to as inflammatory fibrosarcoma, is a rare tumor composed of myofibroblastic spindle cells of uncertain etiology and disputed nosology.
We report a case of inflammatory myofibroblastic tumor of the omentum with involvement of the bone marrow in an 18-year-old man. Histologic and immunohistochemical studies of the abdominal mass and bone marrow were consistent with inflammatory myofibroblastic tumor. Additionally, fluorescence in situ hybridization using a probe specific for the ALK gene showed disruption of the gene.
The literature is reviewed with emphasis on the ability of inflammatory myofibroblastic tumor to recur, metastasize, and cause mortality.
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