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Pathology – Research and Practice 204 (2008) 857–861

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TEACHING CASES

Inflammatory malignant fibrous histiocytoma of kidney: A case report

Amrita Ghosha,�, U.S. Dwivedib, Abhay Kumarb

aDepartment of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, IndiabDepartment of Urology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India

Received 4 June 2007; accepted 28 March 2008

Abstract

Among the renal sarcomas, inflammatory malignant fibrous histiocytoma (MFH) is an extremely rare presentation.A 45-year-old woman presented with acute retention urine following an episode of gross hematuria. Computerizedtomography showed a solid mass at the lower pole of the left kidney. The patient underwent left nephrectomy.Histologically and immunohistochemically, the tumor was diagnosed as an inflammatory subtype of MFH.

Histological appearances of inflammatory MFH vary widely and frequently overlap with benign reactive conditionssuch as Xanthogranulomatous pyelonephritis (XGPN) and malignant lesions, e.g. malignant lymphoma and, lessfrequently, a sarcomatoid variant of renal cell carcinoma. It is important, though difficult, to differentiateinflammatory MFH from these lesions. Careful morphological examination and immunohistochemical findings of thelesion are of great value, in particular in excluding it from its mimics. We discuss the pathological features andchallenges involved in differentiating inflammatory MFH from its masquerader.r 2008 Elsevier GmbH. All rights reserved.

Keywords: Renal sarcoma site; Inflammatory malignant fibrous histiocytoma; Malignant fibrous histiocytoma; Xantho-

granulomatous pyelonephritis

Malignant fibrous histiocytoma (MFH) has beenclassically defined as high-grade pleomorphic soft tissuesarcoma of late adult life, predominantly affectingextremities. Infrequent primary localizations in thegenitourinary tract such as bladder, spermatic cord,prostrate, and kidney have been described [5], and arepresumed to arise from the supporting structures ofparenchymal organs. Here, we describe a case ofinflammatory MFH, emphasizing the intricaciesinvolved in its pathological diagnosis, in particular withreference to the renal origin.

e front matter r 2008 Elsevier GmbH. All rights reserved.

p.2008.03.012

ng author. Tel.: +91542 2307515, 2575889;

67568.

ss: amrita_lko@rediffmail.com (A. Ghosh).

Case report

A 45-year-old woman was admitted to hospital withacute retention of urine following an episode ofhematuria for 2 days. She had no other significantcomplaints except for intermittent gross hematuria forthe last 4 months. Bilateral kidney was palpable onballottement; however, no palpable mass was found onphysical examination. Laboratory analysis revealed mildanemia (10.7 gm/dl), leucocytosis (20.9� 109/l) withneutrophilia (P90, L06, E03, M04). Other biochemicalparameters and a previous urine analysis were withinnormal limits. A low attenuating, intracapsular solidmass (7 cm� 4.7 cm� 6.0 cm) compressing the lowerpelvicalyceal system was detected on computerizedtomography (CT) at the lower pole of the left kidney.

ARTICLE IN PRESSA. Ghosh et al. / Pathology – Research and Practice 204 (2008) 857–861858

The preoperative metastatic workup was negative.Suspecting a stage I renal cell carcinoma (RCC), leftradical nephrectomy was performed, and the post-operative course was uneventful.

Nephrectomy specimen showed a pale yellow colored,uncircumcised solid lesion (6.5 cm� 6.0 cm� 4.5 cm)confined to the lower pole of kidney and infiltratingthe respective pelvicalyceal system (Fig. 1). Microscopi-cally, the lesion showed sheets and nodular aggregatesof xanthoma cells admixed with numerous histiocytes,lymphocytes, plasma cells, neutrophils, and eosinophilsinfiltrating the renal parenchyma (Fig. 2). Many atypical(neoplastic) histiocytes, mononuclear and multinu-cleated giant cells with bizarre nucleus, and a fairnumber of atypical mitosis (Fig. 3) were present. Smallareas of necrosis were also noted. The lesion reached therenal capsule; however, the renal vessels, Gerota’sfascia, perinephric fat, and ureter were free of infiltra-tion microscopically. Immunohistochemistry (IHC)revealed diffuse and strong reactivity for vimentin bythe tumor cells, including some of the multinucleatedcells (Fig. 4), and non-reactivity for cytokeratin (CK),CD20, CD15, and CD30. The histiocytes and a fewneoplastic cells were positive for CD-68 (Figs. 5 and 6).Based on these histomorphological and immunohisto-chemical findings, the lesion was categorized as an

Fig. 1. Gross appearance of left renal mass showing a poorly

circumscribed, whitish solid cut surface and focal necrosis.

Fig. 2. Heterogeneous admixture of histiocytes, plasma cells,

and neutrophils (renal tubular epithelium is also present in the

field) (hematoxylin–eosin, original magnification � 100).

inflammatory subtype of MFH of renal origin. Elevenmonths after initial presentation, the patient presentedwith local recurrence, and pulmonary metastasis wasdetected. Two months later, the patient died.

Discussion

Renal sarcomas account for about 2–3% of allmalignant renal tumors, of which leiomyosarcomas arethe commonest, followed by liposarcoma, fibrosarcoma,and rhabdomyosarcoma [12]. Renal MFH are extremelyrare. In general, MFHs are cellular neoplasms with awide range of histological appearances and, on the basisof the predominant cell population, have been furthercategorized into the following four subtypes: storiformpleomorphic, myxoid, giant cell type, and inflammatory[2]. The majority of MFH described in the kidney wereof fibroblastic–pleomorphic type [4], followed by giantcell type. Primary inflammatory MFH of kidney is anunusual presentation, and, so far, there have beendocumented only four [3,9,12,16] out of 52 reportedcases of primary renal MFH described in the literature.This is the fifth case report of a primary inflammatoryMFH arising in kidney.

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Fig. 3. High power view with atypical mitosis (hematoxylin–

eosin, original magnification � 400).Fig. 4. Vimentin-positive, neoplastic cells, and multinucleated

cell (original magnification � 400).

A. Ghosh et al. / Pathology – Research and Practice 204 (2008) 857–861 859

Inflammatory MFH is an unusual variant of MFH,first described by Oberling in 1935 under the termretroperitoneal xanthogranuloma [10]. At present, it isknown as inflammatory malignant fibrous histiocytomathat commonly affects the retroperitonium and, lessfrequently, the extremities [2]. A common histologicaldenominator of the lesions characterized as inflamma-tory MFH is a diffuse and intense acute inflammatoryreaction unassociated with tissue necrosis in combina-tion with bland and anaplastic-appearing histiocytes.The histomorphology of these lesions varies not onlyfrom lesion to lesion and from recurrence to recurrence,but also within the same tumor, where areas of almostpure histiocytic cells could be found adjacent to densefibroblastic foci arranged in storiform pattern (hallmarkof the fibrous histiocytoma). This feature in combina-tion with other cellular components justifies theirinclusion within the fibrous histiocytoma, and is ofgreat help in establishing the diagnosis of inflammatoryMFH [2,6]. Transition to spindled areas and storiformgrowth pattern, however, may be extremely inconspic-uous and may be even absent [1,8]. The present case,displayed transition of histiocytes to spindled cells withtheir fascicles; however, storiform pattern was notidentified in any of the sections examined.

The treacherous aspect of inflammatory MFH is theirbland cytology and inflammatory appearance, especiallyin initial stages and in absence of storiform pattern.Since histiocytes, while having mitoses, do not have anyanaplastic features and appear bland, this may lead tonon-consideration of growth as being malignant or evenneoplastic. Also, despite the presence of areas withstructural anomalies and cell concentration suggestinga malignant tumor, because of pronounced cellularpolymorphism, growth is recognized as inflammatory.In the presence of marked inflammatory infiltrate, themalignant cells are obscured or overlooked. Asso-ciated peripheral leucocytosis often compounds thisproblem. These features can mislead even competentsurgical pathologists, which is reflected as reluctance toconsider these lesions, other than inflammatory reac-tions (for example xanthogranulomatous inflammationor pseudotumor). Inflammatory MFH has beenreported to be misdiagnosed as xanthogranulomatouspyelonephritis (XGPN) [16]. Therefore, the challenge inestablishing the diagnosis of inflammatory MFH israther to consider the diagnosis of inflammatory MFHin these settings.

Initially, the diagnostic approach applied in thepresent case was to identify the lesion as a malignant

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Fig. 5. CD68-positive, multinucleated neoplastic cell (original

magnification � 400).

Fig. 6. CD68-positive, scattered histiocytes (original magnifi-

cation � 400).

A. Ghosh et al. / Pathology – Research and Practice 204 (2008) 857–861860

rather than a non-neoplastic process, i.e., XGPN, etc.,and then to differentiate it from other malignant lesionssuch as malignant lymphoma and a sarcomatoid variantof RCC. The absence of urinary symptoms and urinaryfindings suggestive of urinary tract infection, thepresence of bizarre histiocytes and atypical mitosisrevealed by extensive sampling and careful, thoroughexamination of the lesion under the light microscopeexcluded the possibility of XGPN. Another diagnosticchallenge was to differentiate malignant lymphoma andthe sarcomatoid variant of RCC. It has been claimedthat inflammatory MFHs are in effect misdiagnosedlymphomas [2]. Again, extensive microscopic sectioningof the sample and IHC staining was of immense help.The neoplastic cells in the present case were non-reactivefor the various leukocyte markers (CD15, CD30, CD20,CD45), cytokeratin (CK), and desmin. The cellsexpressed reactivity for vimentin. In addition, CD68-positive histiocytes and a fair number of neoplasticmultinucleated hisitocytes were also discerned. It hasbeen suggested that CD68 reactivity of neoplastic cellsmight be a reflection of their phagocytic activity [2].Some authors recommend the use of electron micro-scopy (EM) [11] to establish the diagnosis, but othersbelieve that EM investigation is of limited value, being

incapable of distinguishing epithelial or histiocyticfeatures [13]. In the present case, an IHC method wasused to establish the diagnosis.

Histogenesis of MFH is controversial, and it isdebated whether it is fibroblastic or histiocytic; atpresent, it is considered fibroblastic [2]. Nevertheless,in the present case, IHC showed markers characteristicof both mesenchymal cells and a mononuclear phago-cytic system. Considering the above findings, it would beinteresting to determine whether categorization of theinflammatory MFH is justified along with other variantsof MFH (pleomorphic sarcoma), or whether it repre-sents MFH in its true sense.

The clinical presentation of primary renal MFH isusually that of an abdominal lump [4]. Hematuria israrely associated (reported only twice [7,14]) with renalMFH in contrast to the renal cell carcinomas, where it isa presenting symptom in 62% of the cases [15]. Most ofthe renal MFHs arise from the renal capsule; hence,intracavitary progression and consecutive hematuria arerare [17]. In the present case, the lesion was within renalparenchyma, infiltrating the pelvicalyceal system; there-fore, the primary presentation was that of hematuria.Acute retention of urine, secondary to hematuria, led toan acute presentation of this patient, or the patient

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might have remained asymptomatic and thereafterpresented with an aggressive course. Another interestingand unusual feature documented in the cases ofinflammatory MFH and other variants of MFHis associated leucocytosis either as neutrophilia(also observed in the present case) or eosinophilia andfever [2]. These paraneoplastic signs and symptoms,attributed to the production of cytokines by the tumor[2], can also mislead the clinician/pathologist to considerthe lesion as being inflammatory, especially whendealing with inflammatory MFH.

Radical surgical removal offers the only curativeoption [2]. If complete resection fails, the tumor resultsin poor prognosis, either as local recurrence and/ordistant metastasis in particular to lungs and lymphnodes [5]. The present case manifested local recurrenceand distant metastasis even after complete resection ofthe tumor. Although MFH appears to be chemosensi-tive, in particular for doxorubicin- and ifosamide-basedtreatment regimens, the results of adjuvant chemother-apy regarding the survival rate are contradictory [12].Definitive assessment of the role of adjuvant chemother-apy and/or of radiotherapy is not possible due to thesmall number of cases. Differentiation of MFH fromother renal tumors seems to be appropriate as theselesions can be aggressive and might have a rapidly fatalcourse as described in the present case. More documen-ted reports are needed to establish any significantdifference that may exist between primary renal tumorand renal MFH.

To conclude, inflammatory MFH is an extremely rareprimary tumor of kidney, and is the fifth documentedcase in the literature. The histomorphology of inflam-matory MFH is quite variable and may masqueradelesions ranging from a reactive (benign/inflammatory)lesion to epithelial or lymphoid malignancy. Hence, thediagnostic approach to inflammatory MFH includesconsideration of this entity when dealing with a lesionresembling XGPN, and excluding other malignantlesions with the help of IHC. Although these lesionsare obviously aggressive and malignant, it still needs tobe clarified to what extent they (i.e., inflammatoryMFH) are comparable to other subtypes of MFH andother primary renal tumors, histologically, histogeneti-cally and prognostically.

Acknowledgments

The authors sincerely thank Dr Vinita Agarwal,Assistant Professor, Sanjay Gandhi Postgraduate Instituteof Medical Sciences, Lucknow for assistance and co-operation with the immunohistochemical investigations.

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