Pulmonary inflammatory myofibroblastic tumor associated with histoplasmosis
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a Division of General Thoracic Surgery, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905, USA
b Pulmonary Medicine and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Abstract
Inflammatory myofibroblastic tumors of the lung in children are a non-neoplastic process characterized by an unregulated proliferation of inflammatory cells. The etiology of these ‘tumors’ is not certain and often difficult to ascertain. The current understanding of the pathophysiology of this lesion is based on an abnormal response by the myofibroblast to tissue injury. The vigorous immunologic response observed is commonly ascribed to a viral or foreign antigen–antibody interaction. We describe the case of an 8-year-old boy with inflammatory myofibroblastic tumor of the lung clearly associated with newly acquired infection due to histoplasma capsulatum and we review the current pertinent literature.
Key Words: Myofibroblastic tumor; Pseudotumor; Histoplasmosis
1. Introduction
Inflammatory myofibroblastic tumor (IMT), also frequently referred to as inflammatory pseudotumor or plasma cell granuloma, is the most common benign primary lung tumor encountered in children [1]. Typically this non-neoplastic process is distinguished by an unregulated proliferation of inflammatory cells. Often the etiology of this inflammatory phenomenon is uncertain or difficult to determine. The pathophysiologic basis for this lesion, as currently understood, involves an abnormally vigorous immunologic response by spindle cells, primarily myofibroblasts, to local tissue injury. Viral antigens or foreign antigen–antibody interactions are the most commonly implicated sources for the immunologic response. Frequently, however, no specific inciting agent can be uncovered.
The incidence of pulmonary IMT has been reported to be as high as 0.7% of thoracic surgical resections [1]. A previous review from our institution, using strict diagnostic criteria, found an incidence of 0.04% [2].
Certain investigators hold that IMT is a neoplastic process and manifesting as a soft-tissue/mesenchymal tumor with an indeterminate or low malignant potential. In few cases of IMT, cytogenetic analysis has demonstrated the presence of clonal chromosomal aberrations indicating that IMT may be a neoplastic proliferation [3]. One-third to one half of IMT cases present with a 2p23 rearrangement involving anaplastic lymphoma kinase (ALK) often fused with tropomyosin genes TPM3 and TPM4 and the clarithrin heavy chain gene (CLTC) [4]. However, the lack of p53 detection in IMT coupled with the low proliferation index (Ki67 <10%) suggests that IMT may be a low-grade sarcoma, if at all [5]. Nonetheless, Donner and colleagues have described progression of IMT to sarcoma in 7% of pulmonary occurrences [6].
Whether or not this type of tumor is classified as non-neoplastic or frankly malignant, there is clear evidence that these lesions can continue to grow, leading to the potential for significant morbidity [1].
We describe the case of an 8-year-old boy with IMT which was directly associated with pulmonary histoplasmosis.
2. Case report
An 8-year-old boy initially presented to another institution with left-sided chest pain. He was otherwise well and had no physical findings other than dullness to percussion and decreased breath sounds in the left upper lung field. His work-up included normal blood tests (complete blood count, electrolytes, liver transaminases) and fungal serologies which were negative. His chest radiograph and computed tomography scan (Fig. 1A and B) demonstrated a 7 cm x 7 cm x 4 cm mass in the left upper lobe of the lung. A left thoracotomy was performed to resect the mass, at which time the lesion was found to encompass the entire left upper lobe. Due to its central extension, the mass was deemed unresectable. An incisional biopsy was done and the patient was referred to our institution for further care.
The biopsy results revealed a proliferation of spindle cells and specifically myofibroblasts. In addition, the lesion stained positive for the presence of histoplasma organisms without granulomatous inflammation. We subsequently performed a redo left thoracotomy. Following an extensive lysis of adhesions, the mass was found to encompass the entire left upper lobe. A left upper lobectomy was completed along with a mediastinal lymphadenectomy. The completely resected mass was found to be an inflammatory myofibroblastic tumor with associated histoplasma organisms in the pulmonary component (Fig. 2A–C). All lymph nodes from the mediastinal lymphadenectomy were uninvolved, though interlobar lymph nodes within the lobectomy specimen demonstrated a similar inflammatory process as well as containing associated histoplasma organisms. The patient recovered uneventfully from surgery and was treated with oral itraconazole for 3-months following surgery. He has continued to do well 3 years after his definitive procedure with no signs or symptoms of recurrence.
3. Discussion
Inflammatory myofibroblastic tumors are uncommon with at least 50% occurring in patients under the age of 16 years. IMT is the most frequently diagnosed primary lung tumor in the pediatric population. It has not shown any sex predilection, affecting boys as often as girls. Symptoms are generally non-specific, with up to 40% of reported cases occurring without any discernible symptoms.
Chest radiography typically demonstrates a solitary, well-demarcated peripheral lung mass. Previously reported lesions have ranged in size from 1 to 15 cm in diameter. Calcifications are more commonly found in children and can be punctate, curvilinear, dense or dispersed in nature. Cavitation is exceedingly rare. Hilar and mediastinal adenopathy is also very uncommon.
The etiology of IMT is thought to be an uncontrolled response to tissue damage or chronic inflammation. It has been previously suggested that the process leading to IMT of the lung originates as an organizing intra-alveolar pneumonia [7]. In the case presented herein, the inciting injury would appear to be related to the pulmonary infection with histoplasmosis. Not only the organism was identified within the parenchymal lesion but also within the regional lymph nodes.
Only two other reports exist in the medical literature suggesting an association of IMT with histoplasmosis [8,9]. In the report by Frey and associates, the fungal organisms were found only in associated lymph nodes and not within the IMT lesion itself. Gariepy and colleagues describe an elderly female with a left lower lobe IMT and positive histoplasmosis serology. However, no organisms were isolated in culture or able to be observed histologically in the specimen following curative left lower lobectomy.
The case presented represents the only published account of IMT with intralesional histoplasma organisms isolated. Clearly, there are no established guidelines to direct adjuvant treatment in this particular situation. We elected to provide 3 months of adjuvant antifungal medication (itraconazole).
Pulmonary IMT generally requires surgical resection for treatment. A complete resection should be the surgical goal, since local recurrence or distant metastases are only observed following incomplete resection of the primary lesion. Nevertheless, pulmonary conservation should be attempted given the generally non-aggressive nature of this tumor [2]. Long-term follow-up is highly recommended as remote recurrences have been reported [10]. Re-section should be offered to patients who are operable and resectable.
Corticosteroids have been employed for treatment of recurrence or unresectable mediastinal invasion. Response to chemotherapy or radiotherapy has not been well studied. Overall prognosis depends on the extent of local invasion, completeness of surgical resection and presence of aneuploidy in the tumor.
References
Bahadori M, Liebow A. Plasma cell granulomas of the lung. Cancer 1973; 31:191–208.
Cerfolio RJ, Allen MS, Nascimento AG, Deschamps C, Trastek VF, Miller DL, Pairolero PC. Inflammatory pseudotumors of the lung. Ann Thorac Surg 1999; 67:933–936.
Su LD, Atayde-Perez A, Sheldon S, Fletcher JA, Weiss SW. Inflammatory myofibroblastic tumor: cytogenetic evidence supporting clonal origin. Mod Pathol 1998; 11:364–368.
Cook JR, Dehner LP, Collins MH, Ma Z, Morris SW, Coffin CM, Hill DA. Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study. Am J Surg Pathol 2001; 25:1364–1371.
Meis-Kindblom JM, Kjellstrom C, Kindblom LG. Inflammatory fibrosarcoma: update, reappraisal, and perspective on its place in the spectrum of inflammatory myofibroblastic tumors. Semin Diagn Pathol 1998; 15:133–143.
Donner LR, Trompler RA, White RR. Progression of inflammatory myofibroblastic tumor (inflammatory pseudotumor) of soft tissue into sarcoma after several recurrences. Hum Pathol 1996; 27:1095–1098.
Matsubara O, Tan-Liu NS, Kenney RM, Mark EJ. Inflammatory pseudotumors of the lung: progression from organizing pneumonia to fibrous histiocytoma or to plasma cell granuloma in 32 cases. Hum Pathol 1994; 19:807–814.
Gariepy G, Poitras P, Charbonneau R. Granulome plasmocytaire du poumon. Union Med Can 1975; 105:77–81.
Frey A, Eichfeld U, Schubert S, Friedrich T, Schonfelder M. Inflammatorischer pseudotumor der lunge bei hiluslymphknotenhistoplasmose. Chirurg 1998; 69:1101–1104.
Wienberg PB, Bromberg PA, Askin FB. ‘Recurrence’ of a plasma cell granuloma 11 years after initial resection. South Med J 1987; 80:519–521.(Stephen D. Cassivi, and M)
b Pulmonary Medicine and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Abstract
Inflammatory myofibroblastic tumors of the lung in children are a non-neoplastic process characterized by an unregulated proliferation of inflammatory cells. The etiology of these ‘tumors’ is not certain and often difficult to ascertain. The current understanding of the pathophysiology of this lesion is based on an abnormal response by the myofibroblast to tissue injury. The vigorous immunologic response observed is commonly ascribed to a viral or foreign antigen–antibody interaction. We describe the case of an 8-year-old boy with inflammatory myofibroblastic tumor of the lung clearly associated with newly acquired infection due to histoplasma capsulatum and we review the current pertinent literature.
Key Words: Myofibroblastic tumor; Pseudotumor; Histoplasmosis
1. Introduction
Inflammatory myofibroblastic tumor (IMT), also frequently referred to as inflammatory pseudotumor or plasma cell granuloma, is the most common benign primary lung tumor encountered in children [1]. Typically this non-neoplastic process is distinguished by an unregulated proliferation of inflammatory cells. Often the etiology of this inflammatory phenomenon is uncertain or difficult to determine. The pathophysiologic basis for this lesion, as currently understood, involves an abnormally vigorous immunologic response by spindle cells, primarily myofibroblasts, to local tissue injury. Viral antigens or foreign antigen–antibody interactions are the most commonly implicated sources for the immunologic response. Frequently, however, no specific inciting agent can be uncovered.
The incidence of pulmonary IMT has been reported to be as high as 0.7% of thoracic surgical resections [1]. A previous review from our institution, using strict diagnostic criteria, found an incidence of 0.04% [2].
Certain investigators hold that IMT is a neoplastic process and manifesting as a soft-tissue/mesenchymal tumor with an indeterminate or low malignant potential. In few cases of IMT, cytogenetic analysis has demonstrated the presence of clonal chromosomal aberrations indicating that IMT may be a neoplastic proliferation [3]. One-third to one half of IMT cases present with a 2p23 rearrangement involving anaplastic lymphoma kinase (ALK) often fused with tropomyosin genes TPM3 and TPM4 and the clarithrin heavy chain gene (CLTC) [4]. However, the lack of p53 detection in IMT coupled with the low proliferation index (Ki67 <10%) suggests that IMT may be a low-grade sarcoma, if at all [5]. Nonetheless, Donner and colleagues have described progression of IMT to sarcoma in 7% of pulmonary occurrences [6].
Whether or not this type of tumor is classified as non-neoplastic or frankly malignant, there is clear evidence that these lesions can continue to grow, leading to the potential for significant morbidity [1].
We describe the case of an 8-year-old boy with IMT which was directly associated with pulmonary histoplasmosis.
2. Case report
An 8-year-old boy initially presented to another institution with left-sided chest pain. He was otherwise well and had no physical findings other than dullness to percussion and decreased breath sounds in the left upper lung field. His work-up included normal blood tests (complete blood count, electrolytes, liver transaminases) and fungal serologies which were negative. His chest radiograph and computed tomography scan (Fig. 1A and B) demonstrated a 7 cm x 7 cm x 4 cm mass in the left upper lobe of the lung. A left thoracotomy was performed to resect the mass, at which time the lesion was found to encompass the entire left upper lobe. Due to its central extension, the mass was deemed unresectable. An incisional biopsy was done and the patient was referred to our institution for further care.
The biopsy results revealed a proliferation of spindle cells and specifically myofibroblasts. In addition, the lesion stained positive for the presence of histoplasma organisms without granulomatous inflammation. We subsequently performed a redo left thoracotomy. Following an extensive lysis of adhesions, the mass was found to encompass the entire left upper lobe. A left upper lobectomy was completed along with a mediastinal lymphadenectomy. The completely resected mass was found to be an inflammatory myofibroblastic tumor with associated histoplasma organisms in the pulmonary component (Fig. 2A–C). All lymph nodes from the mediastinal lymphadenectomy were uninvolved, though interlobar lymph nodes within the lobectomy specimen demonstrated a similar inflammatory process as well as containing associated histoplasma organisms. The patient recovered uneventfully from surgery and was treated with oral itraconazole for 3-months following surgery. He has continued to do well 3 years after his definitive procedure with no signs or symptoms of recurrence.
3. Discussion
Inflammatory myofibroblastic tumors are uncommon with at least 50% occurring in patients under the age of 16 years. IMT is the most frequently diagnosed primary lung tumor in the pediatric population. It has not shown any sex predilection, affecting boys as often as girls. Symptoms are generally non-specific, with up to 40% of reported cases occurring without any discernible symptoms.
Chest radiography typically demonstrates a solitary, well-demarcated peripheral lung mass. Previously reported lesions have ranged in size from 1 to 15 cm in diameter. Calcifications are more commonly found in children and can be punctate, curvilinear, dense or dispersed in nature. Cavitation is exceedingly rare. Hilar and mediastinal adenopathy is also very uncommon.
The etiology of IMT is thought to be an uncontrolled response to tissue damage or chronic inflammation. It has been previously suggested that the process leading to IMT of the lung originates as an organizing intra-alveolar pneumonia [7]. In the case presented herein, the inciting injury would appear to be related to the pulmonary infection with histoplasmosis. Not only the organism was identified within the parenchymal lesion but also within the regional lymph nodes.
Only two other reports exist in the medical literature suggesting an association of IMT with histoplasmosis [8,9]. In the report by Frey and associates, the fungal organisms were found only in associated lymph nodes and not within the IMT lesion itself. Gariepy and colleagues describe an elderly female with a left lower lobe IMT and positive histoplasmosis serology. However, no organisms were isolated in culture or able to be observed histologically in the specimen following curative left lower lobectomy.
The case presented represents the only published account of IMT with intralesional histoplasma organisms isolated. Clearly, there are no established guidelines to direct adjuvant treatment in this particular situation. We elected to provide 3 months of adjuvant antifungal medication (itraconazole).
Pulmonary IMT generally requires surgical resection for treatment. A complete resection should be the surgical goal, since local recurrence or distant metastases are only observed following incomplete resection of the primary lesion. Nevertheless, pulmonary conservation should be attempted given the generally non-aggressive nature of this tumor [2]. Long-term follow-up is highly recommended as remote recurrences have been reported [10]. Re-section should be offered to patients who are operable and resectable.
Corticosteroids have been employed for treatment of recurrence or unresectable mediastinal invasion. Response to chemotherapy or radiotherapy has not been well studied. Overall prognosis depends on the extent of local invasion, completeness of surgical resection and presence of aneuploidy in the tumor.
References
Bahadori M, Liebow A. Plasma cell granulomas of the lung. Cancer 1973; 31:191–208.
Cerfolio RJ, Allen MS, Nascimento AG, Deschamps C, Trastek VF, Miller DL, Pairolero PC. Inflammatory pseudotumors of the lung. Ann Thorac Surg 1999; 67:933–936.
Su LD, Atayde-Perez A, Sheldon S, Fletcher JA, Weiss SW. Inflammatory myofibroblastic tumor: cytogenetic evidence supporting clonal origin. Mod Pathol 1998; 11:364–368.
Cook JR, Dehner LP, Collins MH, Ma Z, Morris SW, Coffin CM, Hill DA. Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study. Am J Surg Pathol 2001; 25:1364–1371.
Meis-Kindblom JM, Kjellstrom C, Kindblom LG. Inflammatory fibrosarcoma: update, reappraisal, and perspective on its place in the spectrum of inflammatory myofibroblastic tumors. Semin Diagn Pathol 1998; 15:133–143.
Donner LR, Trompler RA, White RR. Progression of inflammatory myofibroblastic tumor (inflammatory pseudotumor) of soft tissue into sarcoma after several recurrences. Hum Pathol 1996; 27:1095–1098.
Matsubara O, Tan-Liu NS, Kenney RM, Mark EJ. Inflammatory pseudotumors of the lung: progression from organizing pneumonia to fibrous histiocytoma or to plasma cell granuloma in 32 cases. Hum Pathol 1994; 19:807–814.
Gariepy G, Poitras P, Charbonneau R. Granulome plasmocytaire du poumon. Union Med Can 1975; 105:77–81.
Frey A, Eichfeld U, Schubert S, Friedrich T, Schonfelder M. Inflammatorischer pseudotumor der lunge bei hiluslymphknotenhistoplasmose. Chirurg 1998; 69:1101–1104.
Wienberg PB, Bromberg PA, Askin FB. ‘Recurrence’ of a plasma cell granuloma 11 years after initial resection. South Med J 1987; 80:519–521.(Stephen D. Cassivi, and M)