Case 4 -

Inflammatory Pseudotumor Syed Z. Ali The Johns Hopkins Hospital Baltimore, MD

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Clinical History: 52 year-old man, nonprogressive HIV+ and HCV+ with history of syphilis and gonorrhea now presents with a 1.6 cm left upper lobe lung mass with positive PET scan. CT-guided FNA. Cytologic Diagnosis: Consistent with Inflammatory Pseudotumor Histologic Diagnosis: Inflammatory Pseudotumor Cytologic Findings: Smears show extreme hypercellularity with predominantly tissue fragments and few isolated background cells. A mixed inflammatory infiltrate composed of lymphocytes, histiocytes, plasma cells and neutrophils is characterisitc. In addition, atypical cytologic features are also observed in the background histiocytes such as pleomorphic nuclei, high nuclear/cytoplasmic ratio, well-formed nuclear grooves, intranuclear inclusions and multinucleation. Rare areas display predominance of plasma cells associated with an exuberant fibroblastic reaction with microvascular proliferation and granulation tissue formation. Pronounced focal cytologic atypia is present in the spindled fibroblastic and endothelial cells with occasional mitoses, cellular pleomorphism and prominent nucleoli. Case 4 - Figure 1 Diff Quik Stain, X40 Case 4 - Figure 2 Diff Quik Stain, X100 Case 4 - Figure 3 Diff Quik Stain, X200 Case 4 - Figure 4 Papanicolaou Stain, X400 Case 4 - Figure 5 Diff Quik stain, X400 Case 4 - Figure 6 Diff Quik Stain, X400 Histologic and Clinical Follow-up: Due to the patient's concern for cancer, a long smoking history and a positive PET scan, a decision was made to perform pulmonary lobectomy. He underwent a flexible bronchoscopy which was normal and an uncomplicated left upper lobectomy and lymph node biopsy Grossly, the lobectomy specimen measuring 17 x 12 x 3 cm, on sectioning revealed a 1.1 cm well circumscribed encapsulated nodule with a brown-red friable center. The nodule was surrounded by a 0.1 cm fibrous capsule. Histologic examination showed an "INFLAMMATORY PSEUDOTUMOR. EIGHT (8) BENIGN LYMPH NODES". The pseudotumor consisted of a walled off mixed inflammatory infiltrate with reactive fibroblasts. The surrounding lung was histologically unremarkable. Last clinical follow-up was in September 2006. He is doing fairly well with long term non-progressive CD4 count between 350-400. Discussion: Inflammatory pseudotumor (IPT) is an extremely rare clinical entity. A disease of uncertain histogenesis and prognosis, IPT is a frequent mimicker of a number of benign inflammatory and neoplastic diseases. IPTs are generally benign mixed inflammatory masses, described in many different organs including the lung and liver. Due to the heterogeneity of the cellular infiltrate, these lesions have also been reported as inflammatory myofibroblastic tumors, plasma cell granulomas, and fibroxanthomas. Although the etiology is largely unknown, IPTs commonly occur following infection, trauma, or other inflammatory reaction. Patients can be asymptomatic or present with constitutional symptoms and abnormal laboratory values including leukocytosis, hypergammaglobulinemia, and an elevated erythrocyte sedimentation rate. The lesions may grow to alarming sizes causing significant pain. IPTs are typically identified, often incidentally, as mass lesions through routine radiographic imaging and their clinical behavior and radiographic appearance often mimic malignant processes. Generally, IPTs have a benign behavior with occasional spontaneous regression, but have been reported to recur, metastasize, and undergo sarcomatous transformation. Diagnosis of IPT by FNA or open biopsy is possible, but challenging, and there are only a few reports in the literature. The morphologic characteristics can be nonspecific and quite variable. The presence of inflammation and spindle cell populations often raises the concern of malignancy. The differential diagnosis for spindle-cell lesions in this context includes sclerosing hemangioma, benign and malignant nerve sheath tumors, sarcomatous carcinoma, melanoma, and high grade sarcomas including malignant fibrous histiocytoma, leiomyosarcoma, and fibrosarcoma. In IPT the spindle cells typically maintain a low nuclear to cytoplasmic ratio, show more reactive than dysplastic nuclear features, and are accompanied by significant inflammation supporting a reactive process. When the spindle cell component of IPT is less pronounced, the differential diagnosis includes hematologic malignancies. Sheets of plasma cells, i.e. plasma cell granuloma, may erroneously lead to a diagnosis of plasmacytoma. When lymphomononuclear cells predominate, lymphoma enters the differential. Even an IPT with a mixed infiltrate may mimic a Hodgkin lymphoma. Although the differential diagnosis for a spindle cell mass with mixed inflammation is long, the diagnosis of IPT can be facilitated with the use of standard criteria for malignancy and immunoperoxidase staining of the cell block sections. The presence of necrosis, atypia, and a high proliferation index would favor a malignant process. IPTs would be cytokeratin negative and reveal heterogeneous cell populations. Lymphocytes and plasma cells will demonstrate polyclonality by kappa/lambda immunohistochemistry and flow cytometric analysis. CD68 or HAM56 can be used to identify histiocytic populations and muscle markers (actin, desmin, myogenin) may highlight the myofibroblasts. Ultrastructurally, the plump spindle cells show features of fibroblastic differentiation [5]. Nonetheless, a diagnosis of IPT is often a diagnosis of exclusion. An accurate recognition and distinction of this entity from primary or metastatic cancers is particularly important in order to avoid unnecessary extensive surgery. References: Horiuchi R, Uchida T, Kojima T, et al: Inflammatory pseudotumor of the liver: clinicopathologic study and review of the literature. Cancer 1990;65:1583-1590 Souid AK, Ziemba MC, Dubansky AS, Mazur M, Oliphant M, Thomas FD, Ratner M, Sadowitz PD: Inflammatory myofibroblastic tumor in children. Cancer 1993;72:2042-2048 Sakai M, Ikeda H, Suzuki N, Takahashi A, Kuroiwa M, Hirato J, Hatakeyama S, Tsuchida Y: Inflammatory pseudotumor of the liver: case report and review of the literature. J Ped Surg 2001;36:663-666 Bakhos R, Wojcik EM, Olson MC: Transthoracic fine-needle aspiration cytology of inflammatory pseudotumor, fibrohistiocytic type: a case report with immunohistochemical studies. Diagn Cytopathol 1998;19:216-220 Shek TWH, Ng IOL, Chan KW: Inflammatory pseudotumor of the liver: report of four cases and review of the literature. Am J Surg Pathol 1993;17:231-238 Malhotra V, Gondal R, Tatke M, Sarin SK: Fine needle aspiration bytologic appearance of inflammatory pseudotumor of the liver. Acta Cytol 1997;33:1325-1328 Thunnissen FB, Arends JW, Buchholtz RT, ten Velde G: Fine needle aspiration cytology of inflammatory pseudotumor of the lung (plasma cell granuloma). Report of four cases. Acta Cytol 1989;33:917-921 Lupovich A, Chen R, Mishra S: Inflammatory pseudotumor of the liver. Report of the fine needle aspiration cytologic findings in a case initially misdiagnosed as malignant. Acta Cytol 1989;22:259-262 Nakama T, Hayashi K, Komada N, Ochiai T, Hori T, Shioiri S, Tsubouchi H: Inflammatory pseudotumor of the liver diagnosed by needle biopsy under ultrasonographic tomography guidance. J Gastroenterol 2000;35:641-645 Hummel P, Cangiarella JF, Cohen J-M, Yang G, Waisman J, Chhieng DC: Transthoracic Fine-Needle Aspiration Biopsy of Pulmonary Spindle Cell and Mesenchymal Lesions. Cancer 2001;93:187-198 Powers CN, Berardo MD, Frable WJ: Fine-Needle Aspiration Biopsy: Pitfalls in the Diagnosis of Spindle-Cell Lesions. Diagn Cytopathol 1994;10:232-240 Kim JH, Chow JH, Park MS, Chung JH, Lee JG, Kim YS, Kim SK, Kim SK, Shin DH, Choi BW, Choe KO, Chang J. Pulmonary inflammatory pseudotumor-a report of 28 cases. Korean J Intern Med 2002;17:252-258