Recurrent inflammatory myofibroblastic tumor of the glottis mimicking malignancy

Case Reports Recurrent Inflammatory Myofibroblastic the Glottis Mimicking Malignancy

Tumor of

Alessandro Corsi, MD, Andrea Ciofalo, MD, Marino Leonardi, MD, Gianpietro Zambetti, MD, and Cesare Bosman, MD

Inflammatory myofibroblastic tumor (IMT), a pseudosarcomatous inflammatory lesion occurring in the soft tissue and viscera of children and young adults, is known by many other terms, including plasma cell granuloma, plasma cell pseudotumor, xanthomatous pseudotumor, pseudosarcomatous myofibroblastic proliferation, inflammatory myofibrohistiocytic proliferation, inflammatory fibrosarcoma, and, most commonly, inflammatory pseudotumor. l-3 Despite the variety of histological presentation, Pettinato et al4 regarded inflammatory pseudotumor as one clinicopathologic entity and called it IMT. IMT has been reported to occur more frequently in the 1ung5-7; extrapulmonic favorite sites are abomen, central nervous system, and both the head and neck,3,8 with the larynx uncommonly involved.3,g-12 The purpose of this paper is to present a new laryngeal IMT identified in a 57-year-old man. It was located in the glottis and recurred z months after excision. Clinical history and morphological findings are elucidated, and the importance of a such diagnosis is stressed, especially in terms of unnecessary aggressive

From the Department of Experimental Medicine and Pathology, Division of Pathology, the Department of Otorhinolaryngology, and the Department of Experimental Medicine and Pathologv, Division of Patholoqv, University La Sapienza, Rome,Italy and lstituto R&over0 e Cura a Carsttere Scientifico-Hosoital Casa Sollievo della Sofferenza, Foggia, Italy. ’ Address reprbnt reqbests to Cesare Bosman, MD, Dipartimento di Medicina Sperimentale e Patologia, Istituto di Anatomia e lstologia Patologica, Universita “La Sapienza,” Policlinico Umberto I, Viale Regina Elena 324,00161 Roma, Italy. Copyright 0 1997 by W.B. Saunders Company 0196-0709/97/l 802-0010$5.00/O American

Journal

of Otolaryngology,

treatment low-up.

and

the

importance

of the

fol-

CASE REPORT A 5i’-year-old Italian man reported a s-month history of progressive hoarseness, shortness of breath, and intermittent disphonia. Because he had been treated with oral antibiotics and corticosteroids without benefit, he was referred to Depart-

ment of Otorhinolaryngology,

University La Sapi-

enza of Rome. Routine laboratory investigations and chest x-ray did not show any abnormalities. Fiberoptic laryngoscopy showed a 0.8-cm submucosal ulcerated nodular mass projecting from the anterior wall of the glottis (anterior commissure) and partially obstructing the lumen. The lesion was completely excised, and histological examination was performed (see below). The patient was referred z months later for the same symptoms. Again, routine laboratory investigations, chest x-ray,

and total body computed tomography did not show any significant abnormalities. Via fiberoptic laryngoscopy, a 0.6-cm submucosal nodular mass was observed at the same site of the first lesion and excised. Because light microscopy of the first lesion had not been resolutive in distinguishing between leiomyosarcoma and IMT, part of the recurrent lesion was processed for ultrastructural examina-

tion (see below). Follow-up examination at 1 year postoperatively did not show any abnormalities in the voice and showed an excellent airway with normal wound healing: recurrences and metastasis were absent. Both excised lesions were fixed in 10% buffered formalin solution, routinely processed, and embedded in paraffin. From each block, sections were cut and stained with hematoxylin-eosin, van Gieson, periodic acid-Schiff reagent (PAS), Masson’s thricrome, and phosphotungstic acid-hematoxylin (PTAH) . For immunohistochemical study, dewaxed and hydrated sections were treated with 0.4% hydrogen peroxidase in absolute methanol (15 minutes at room temperature) to block endogenous peroxidase

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activity and with normal rabbit serum for 20 minutes to reduce background staining. A variety of primary antibodies were used: monoclonal anticytocheratin (Dako-CK, MNFllG), anti-muscle specific actin (Dako-Muscle Actin, HHF35), antidesmin (Dako-Desmin, D33), anti-vimentin (DakoVimentin, Vg), and polyclonal anti-myoglobin (Dako). For electron microscopy, small fragments of the recurrent lesion were fixed in Karnowski solution (2.5% glutaraldehyde solution buffered at pH 7.2 + paraformaldehyde 4% solution buffered at pH 7.2, 0.13 mol/L in equal parts), postfixed in 1% osmium tetroxide, dehydrated in graded ethanol solutions, and embedded in epon 812. Sections were cut with diamond knives in Ultracut ultramicrotome (Leica, Vienna, Austria), placed in uncoated grids, stained with many1 acetate and lead cytrate, and observed via transmission electron microscopy with a 1OC Zeiss electron microscope (Oberkochen, Stuttgart, Germany).

ET AL

indented nuclei containing one, or occasionally more than one, nucleoli and a sparsely distributed chromatin with some condensation towards the nuclear envelope; rough endoplasmic reticulum was prominent. Close aggregation of thin filaments, with intercalated dense bodies, were present in the large part of the spindle cells, either in the cytoplasm or in close apposition with the plasma membrane. Fibronexus, intercellular junction, and an electron-dense substance corresponding to basal lamina were frequently observed. The inflammatory component of the lesion was recognized as well. Based on these features, the diagnosis of leiomyosarcoma was excluded and that of IMT confirmed. DISCUSSION

RESULTS Light Microscopy Because the primary lesion and the recurrence had similar histological and immunohistochemical features, they are described together. By conventional histology (Fig l), both lesions were constituted by a compact spindle cell proliferation with a prominent admixture of inflammatory cells. The spindle cells showed large and elongated vesicular nuclei with prominent nucleolus and ill-defined cytoplasmic borders; they were arranged in fasicles of various orientation. Nuclear polymorphism was minimal; mitotic figures were not rare, especially in the recurrent lesion. Inflammatory cells, including small lymphocytes, histiocytes, plasma cells, and neutrophils, permeated bundles of collagen. The intercellular stroma was focally myxoid. Both lesions extended to the subepithelial connective tissue. Spindle cells did not show striations on PTAH stain, and, according to immunohistochemistry results, they were immunoreactive for muscle-specific actin and vimentin. Such features were considered an inflammed-infected

consistent

either

leiomyosarcoma

with

or

with an IMT. Ultrastructural

Microscopy

The spindle cell component showed features of fibroblasts and myofibroblasts (Figs 2 and 3). Such cells were characterized by deeply

IMT is a pseudosarcomatous inflammatory lesion occurring in the soft tissues and viscera, mainly in the lung, of children and young adults, and better known as inflammatory pseudotumor.’ Because the term “pseudotumor” reflects the clinicoradiological presentation of a space occupying nonneoplastic lesion, it has been used for any mass lesion mimicking neoplasm. Especially with respect to the larynx, it has been used either when a histological examination was not performed or to describe laryngeal polyps or lymphoid hyperplasia.13-l6 In their series of 84 cases, Coffin et al3 stress that extrapulmonary IMTs affect patients between the ages of 3 months to 46 years with mean and median of 9.7 and 9 years, respectively. The larynx is not a typical site of origin for IMT; in the same series, only three cases

developed at this site. Few other cases of the larynx have been reported in the literature.g-12 In the largest series, Wenig et all2 reported the clinicopathologic features of eight cases of IMT of the larynx, six of which developed in the glottis: the age of the patients ranged from 19 to 69 years with a median of 59; only one patient had recurrence. Three main histological patterns, though not equally represented in each tumor, characterize

IMT:

a myxoid,

vascular,

and inflamma-

tory pattern; a compact spindle cell pattern with intermingled inflammatory cells: and a collagenous pattern. 3 Such features can mimick a long list of spindle cell lesions including

Figl. Paraffin sections of the tumor showing (A) an highly cellular spindle ceil pre liferation with a patchy mom+ nuclear infiltrate (hematoxylineosin; original magnification x70), (B) extension to the subepithelial connective tissue of the glottis (hematoxylin-eosin; original magnification x90, and (C) mitotic figures (hematoxylineosin; original magnification X160). Note that A and B are from the first lesion, and C is from the recurrent lesion.

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Fig 2. Electron microscopy of the recurrent lesion. Lowpower magnification showing spindle ceils with features of myofibroblasts (uranyl acetate, lead citrate; original magnification ~5,720).

nodular fasciitis, fibromatosis, myofibroblastoma, fibrous histiocytoma, inflammatory malignant fibrous histiocytoma, sarcomatoid carcinoma, spindle cell squamous carcinoma, and benign and malignant smooth muscle tumors. Based on these features, the histopathological diagnosis can be extremely difficult, and adjunctive diagnostic technique (immunohistochemistry and ultrastructure) are usually necessary in the differential diagnosis. In the case reported here, the main pattern was the second; light microscopic features of the first lesion were consistent either with inflammed-infected leiomyosarcoma or with an IMT. Because the ultrastructural study, performed on the recurrent lesion, showed that the spindle cells were fibroblasts and myofibroblasts and did not indicate the features of myoid differentiation, the diagnosis of leyomyosarcoma was excluded and that of IMT confirmed. 3,4~17-1g

Altough considered in the spectrum of socalled pseudosarcomatous lesions as nonneoplastic mesenchymal proliferation,*l IMT appears to be a neoplasm of limited, but urnpredictable, biological potential with a relatively high incidence of recurrence.3Jo There is no consensus about its capacity of recurrence and metastatization, because it is uncertain whether lesions involving multiple sites represent multifocal disease or distant metastasis.2* Because a recurrence and a metastatic rate of 37% and ll%, respectively, have been reported in a histologically related lesion classified as inflammatory fibrosarcoma,2 IMT and inflammatory fibrosarcoma are considered synonymously both in the last World Health Classification of soft tissue tumor+ and in the classification of soft tissue tumors used by Enzinger and Weiss” in their text. Based on their experience, Wenig et all2 “do not believe that laryngeal IMT should be considered analo-

INFLAMMATORY

MYOFIBROBLASTIC

TUMOR

Fig 3. Ultrastructural details of two myofibroblasts. (A) indented nucleus, subplasmalemmal fascicles of thin filaments (asterisk), and focal thickening of basal membrane (arrow) (uranyl acetate, lead citrate; original magnification x9,500). (B) an intercelluar junction (arrowhead) and intracytopasmic thin filaments with intercalated dense bodies (asterisk) (uranyl acetate, lead citrate; original magnffication ~17,888).

gous to the soft tissue neoplasms reported by Meis and Enzinger, [2]“, because only one of their eight cases had a recurrence; they considered laryngeal IMT “indolent, nonmetastasizing lesions that rarely may recur locally or are multifocal.” Our case confirms the impressions of Wenig et all2 because recurrence developed locally and quickly in the absence of metastasis or multifocality. In addition, our experience con-

firms that ultrastructural examination can be an adjunctive diagnostic technique that is useful in the recognition of such lesions and in the discrimination between sarcoma and carcinoma. Aside from the sites of origin, many issues about IMT, such as etiology or biological behavior, are actually unresolved. Although IMT has been considered a neoplastic lesion with a generally benign clinical behavior, in the lar-

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ynx it must be recognized and differentiated from malignant neoplasms to avoid unnecessary aggressive treatment. In addition, the term IMT should be preferred to either inflammatory pseudotumor/plasma cell granuloma when the predominant cell is myofibroblast, or to inflammatory fibrosarcoma because, like in a misdiagnosis of malignancy, it may well lead to unnecessary aggressive treatment. However, based on the potential capacity to recur, as shown by the case reported here and by one of the cases of Wenig et a1,12a diagnosis of IMT should alert the clinicians to accurately follow-up affected patients, because there are no morphological features that can predict its biological behavior. REFERENCES 1. Brunn J: Two interesting benign lung tumors of contradictory histopathology. J Thorac Surg 9:119-131, 1939 2. Meis JM, Enzinger FM: Inflammatory fibrosarcoma of the mesentery and retroperitoneum. Am J Surg Path01 15:1146-1156,1991 3. Coffin CM, Watterson J, Priest JR, et al: Extrapulmonary inflammatory myofibroblastic tumor (Inflammatory pseudotumor). Am J Surg Path01 19:859-872,1995 4. Pettinato G, Manivel JC, De Rosa N, et al: Inflammatory myofibroblastic tumor [plasma cell granuloma). Clinicopathologic study of 20 cases with immunohistochemical and ultrastructural observations. Am J Clin Path01 94:538-546,199O 5. Bahadori M, Liebow AA: Plasma cell granuloma of the lung. Cancer 31:191-208,1973 6. Spencer H: The pulmonary plasma celllhistiocytoma complex. Histopathology 8:903-916,1984 7. Matsubara 0, Tan-Liu NS, Kenney RM, et al: Inflammatory pseudotumors of the lung: Progression from organizing pneumonia to fibrous histiocytoma or to plasma cell granuloma. Hum Path01 19:807-814, 1988 8. Treissman SP, Gillis A, Lee CLY, et al: Omentalmesenteric inflammatory pseudotumor. Cytogenetic dem-

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