Inflammatory Pseudotumors in Children

By Leslie Scott, Geoffrey Blair, Glen Taylor, James Dimmick, and Graham Fraser Vancouver, British Columbia

�9 Inflammatory psoudotumors are so named because they mimic malignant tumors clinically and radiologically. Most often seen in the lungs of young adults, they consist of localized proliferations of mononuclear inflammatory cells and myofibroblasts. There are scattered reports of these tumors occurring in various sites in children. We report five cases of these rare lesions in children; four arising intraabdominally and one in the lung. In contrast to the usual presentation in adulthood, these children were all previously healthy. One child, with the tumor arising from the urinary bladder, was originally diagnosed as having a malignant sarcoma and underwent pelvic exenteration and chemotherapy for this subsequently-proven benign lesion. Local recurrence occurred in one case. Total excision is indicated and is usually possible without unacceptable morbidity. Our cases and a review of the literature point out the importance of pathologic differentiation of these lesions from malignancy with early appropriate surgery. �9 1988 by Grune & Strat ton, Inc.

INDEX WORDS: Inflammatory pseudotumor; plasma cell granuloma.

also normal. Serum immunoglobulins were measured in two patients. One had elevated IgG and IgA levels, and the other had an increased IgM fraction. Bone marrow aspirates revealed a reactive marrow in all children. One aspirate showed moderate plasmacytosis and another eosinophilia.

Radiologic investigations for the child with the lung lesions included chest x-ray, fluoroscopy, and tomograms. These demon- strated a solid mass obliterating the right upper lobe. It was unclear whether the mass was intrapulmonary or extrapulmonary in origin.

All four intraabdominal lesions were well-demonstrated by use of ultrasound. The tumors were all large; two were felt to contain areas of necrosis or hemorrhage, and one had prominent calcification. Intravenous pyelography was done in two patients, showing a bladder tumor and right hydronephrosis in one, and bilateral ureteral compression from a suprapubic tumor in the other. Compu- terized tomography (CT) scan was done in three cases, confirming what was seen on ultrasound, and identifying displacement and compression of the aorta and inferior vena cava in two patients. The metastatic workup included chest x-ray, bone scan, liver-spleen scan, and skeletal surveys in three patients. No evidence of metastat ic disease was found in any patient. The tumors were found to have vascular enhancement, but no technetium uptake.

I N F L A M M A T O R Y pseudotumors are rare, benign solid lesions so named because they mimic malig-

nant tumors clinically and radiologically. However, the name is misleading as the lesions are not proven to be postinflammatory in origin, and they are true tumors. They are found most commonly in the lung, but have been described in various other sites.

MATERIALS AND METHODS

We have seen five children with inflammatory pseudotumors since 1977. Interestingly, our two most recent patients were admitted for investigation of abdominal masses within two days of each other.

The children's ages at presentation ranged from 2 years to 6 years, with a mean of 3.8 years. Four children were female and one was male.

The sites of origin of the pseudotumors were right lung, uterus, bladder, pancreas, and sigmoid mesentery.

Of the four children with intraabdominal lesions, two were discovered to have abdominal masses by their mothers. One of these had been unwell for 3 weeks with malaise and intermittent fevers, whereas the other child was completely asymptomatic. One child had recurrent urinary tract infections and persistent hematuria. Only one of the four patients presented with abdominal pain. The child with the lung lesion presented with fever and cough that recurred after completion of a course of antibiotics.

Laboratory investigations revealed that all four children with intraabdominal tumors had hypochromic, microcytic anemia. WBC counts were within normal range, although one child showed a marked eosinophilia. The child with the lung lesion did not have anemia, but did have an elevated WBC count. Three children had a mild thrombocytosis. Serum electrolytes, urea, creatinine, protein, albumin, and a-fetoprotein were within normal range in all children. Urinary VMA collections were obtained in three patients and were

Treatment

On the basis of the clinical, laboratory, and radiologic findings, the preoperative diagnoses listed in Table I were made, and the operative approaches planned accordingly.

Four of the tumors were excised completely at the time of the first operation. The lung tumor was found to occupy the entire upper lobe and encroach on the middle lobe. It extended to the hilum where it was peeled off the main stem bronchus. The right upper lobe bronchus and pulmonary vessels were obliterated by the tumor. Although there was no margin of normal tissue, the tumor was believed to be completely excised.

The uterine tumor had almost completely replaced the uterus, and necessitated hysterectomy for complete removal. The other two tumors were completely excised without resection of other organs. Although these large tumors were adherent to small and large bowel and to major vessels, it was possible to peel them free from these structures.

Upon pathologic examination, it was evident that these four tumors were benign. Three were initially identified as inflammatory pseudotumors. One was labeled a benign mesenchymal tumor aris- ing in the uterus and was later classified as an inflammatory pseudotumor.

A biopsy of the bladder tumor was initially performed through the

From the British Columbia Children's Hospital, Vancouver. Presented at the 19th Annual Meeting o f the Canadian Associa-

tion o f Paediatric Surgeons, Winnipeg, Manitoba, Canada, Septem- ber 9-12, 1987.

Address reprint requests to Geoffrey K. Blair MD, Division o f Pediatric Surgery, British Columbia Children's Hospital, 4480 Oak St, Vancouver, British Columbia, Canada V6H 3V4.

�9 1988 by Grune & Stratton, Inc. 0022-3468/88/2308-0015503.00/0

Journa/ of Pediatric Surgery, Vol 23, No 8 (August), 1988: pp 755-758 755

756 SCOTT ET AL

Table 1. Summary of Characteristics, Diagnoses, and Treatment for B Patients Wi th Inflammatory Pseudotumors

Patient Preoperative Initial No. Age (yr) Site Presentation Diagnosis Pathology Treatment

1 3.5 Right lung Fever, cough TB, lymphoma, neuroblastoma

2 6 Uterus Anemia Ovarian teratoma 3 5 Bladder Anemia, recurrent UTI's Sarcoma

4 2.5 Pancreas Anemia, fever, abdominal Neuroblastoma mass

5 2 Mesentery Abdominal mass Neuroblastoma

Inflammatory pseudotumor

Benign mesenchymal tumor Low-grade leiomyosarcoma

Inflammatory pseudotumor

Inflammatory pseudotumor

Right upper Iobectomy (1977) Right pneumonectomy ( 1981 ) Laparotomy, hysterectomy Cystoscopy, biopsy, chemothera-

py, total cystectomy, hyster- ectomy, pelvic lymphadenec- tomy, ileal conduit

Laparotomy, excision

Laparotomy, excision

Abbreviations: TB, tuberculosis; UTI, urinary tract infection.

cystoscope. The tumor was invading the bladder wall, not involving mucosa. The needle biopsy was reported as a sarcoma of unknown etiology; on this basis, the child underwent two months of preopera- tive chemotherapy (vincristine, actinomycin-D, cyclophosphamide) and subsequent pelvic exenteration. Pathologic examination then showed no invasion of other organs, and negative nodes. The tumor was believed to be a low-grade leiomyosarcoma, and therefore the child underwent further chemotherapy. Of note, the first reported case of pseudotumor arising in the bladder occurred 3 years after her presentation. J

The only recurrence in this series was in the child with the lung lesion. The patient, a boy, returned 4 years later with extensive right lung obliteration and deviation of the mediastinum. He underwent a second thoracotomy, but the tumor had extended around the superior vena cava and encased the pulmonary veins inside the pericardium. Right pneumonectomy was carried out, but gross residual tumor remained. The child received postoperative radio- therapy and was scheduled to continue treatment as an outpatient, but the family refused further radiation and follow-up.

This child is alive and apparently well, but his family refuses medical follow-up. The other four remain free of disease, with follow-up ranging from 7 months to 6 years.

DISCUSSION

Inflammatory pseudotumors were first described in the lung by Brunn in 1939, 2 and were so named by Umiker and Ivorsen 3 in 1954. Since then, these tumors have become recognized as uncommon lesions occur- ring in young adults. In a literature review by Berardi et al, 4 181 inflammatory pseudotumors of the lung were analyzed. The average patient age was 29.5 years, and 8.1% were between 1 and 10 years of age.

Abdominal inflammatory pseudotumors were first recognized and reported by Pack and Baker 5 in 1953 who described one arising in the liver, and by Soga et al 6 in 1970 who describe one arising in the stomach.

Since then, there have been scattered case reports describing tumors arising in the stomach, 7 spleen, s bladder, t small bowel mesentery, 9 pancreas, l~ kidney, 11 thyroid, lz spinal cord meninges, 13 and even intracranial duraJ 4 Of these reported extrapulmonary cases, only two were in children. 9'~5 However, a recent abstract by Dehner 16 describes a collection of 22 extrapulmonary

inflammatory pseudotumors in which the average patient age is 12 years, indicating that this may be an increasingly recognized tumor in children.

Grossly, these tumors are often large solid masses with smooth glistening surfaces. The diameter in our series ranged from 6.0 to 13.0 cm, which is consistent with the literature. 16 They may arise from an organ on a vascular peritoneal pedicle as noted in two of our cases, or they may infiltrate the structure of origin to a variable extent as was evident in our cases arising in the uterus, bladder, and lung. They are often densely adherent to surrounding organs, but can usually be peeled away without injury to, or resection of, those organs. When cut they are yellow-tan to greyish white in color, usually firm often with nodular fibrotic changes, and occasionally with areas of calcifcation (Fig 1).

With regard to histology, these lesions are benign localized proliferations of mononuclear inflammatory cells and "spindle cell' mesenchymal cells or myofibro- blasts. The inflammatory cell component may be pre- dominantly plasma cells, lymphocytes, or eosinophils.

Fig 1. Inflammatory pseudotumor arising from the anterior surface of the pancreas, measuring 13 • 10 x 7 cm. The exterior is smooth and bosselated, and the cut surface is firm with a slightly whorled texture.

INFLAMMATORY PSEUDOTUMORS IN CHILDREN 757

Fig 2. Microscopic section of inflammatory pseudotumor of the lung shewing storiform pattern, spindle cells, mononuclear inflammatory cells, and fibrosis.

There may be a variable component of foamy histio- cytes or mast cells, and frequently there are areas of myxomatous change. The inflammatory cells are mature, and importantly, there is no cellular anaplasia and few mitoses (Figs 2 and 3).

The polymorphic nature of the histology gives rise to confusing terminology. In the lung, depending on the preponderance of plasma cells, foamy histiocytes, or myxomatous change, they are also known as plasma cell granulomas, xanthogranulomas, or xanthofibro- mas (to name only a few). 4

The polymorphic histology also makes diagnosis difficult. If plasma cells are predominant, it is often difficult to distinguish these lesions from plasmacyto- mas; however, immunohistochemistry demonstrates that they consist of polyclonal rather than monoclonal plasma cells. Differentiation from sarcoma and even lymphoma may be difficult as the histologic pattern may be storiform, and the cell predominance may be of the type seen in myosarcomas (as in our bladder tumor case), myxofibrosarcomas, fibrous histiocytomas, or even Hodgkin's lymphoma. Electronmicroscopy can often help distinguish these lesions from malignancies, due to the lack of ultrastructural evidence of neopla- s i a . 17q9

The etiology of these tumors is not defined. Some researchers believe that the tumors arose after trauma, following surgery, after in infection, or in association with a malignancy. Inflammatory pseudotumor has been reported in the stomach in association with gastric ulcer and with gastric carcinoma. 6'7 It has also been reported following camplylobacter jejuni enteri- tis arising in the mid-ileal mesentery. 2~ None of these predisposing factors was present in our patients. None had undergone previous operations or had a history of significant illness or trauma. In Berardi's review of

Fig 3. High-power field of Fig 2 illustrating spindle cells, plasma cells, lymphocytes, end foamy histiocytes,

lung lesions, only 30% had a history of previous lung disease. 4 Bacteria or fungi have never been cultured from a resected tumor, and ultrastructural analysis has not shown viral inclusion bodies in any report. 4'17'2~

Other researchers proposed it was a response to an immunologic process. 7'19 Several case reports docu- ment anemia, fever hypergammaglobulinemia, and thrombocytosis as presenting features of inflammatory pseudotumors. 9'1a'16 This complex was present in one of our patients, and noted by Dehner to be frequently present in tumors arising in mesentery, posterior mediastinum, and porta hepatis. ~6

The myofibroblast seen in these lesions is ultrastruc- turally similar to that seen in immature granulation tissue, and it has been proposed that this lesion may represent a variant of the inflammatory repair pro- ces s . 17,15

Dehner proposes that there is a morphologic and possibly biologic spectrum from nodular fasciitis, through myofibromatosis, inflammatory pseudotumor, to fibrous histocytoma. ~

There has been no report of malignant change arising in an inflammatory pseudotumor. These lesions do not metastasize, and rarely invade adjacent struc- tures. The lesions usually exhibit slow growth, but a rapidly enlarging pulmonary lesion has been described.* Excision of the lesion usually is curative, but recurrence has been documented. The tumor recurred in one of our patients and in two in Berardi's series. Dehner reports two intraabdominal recurrences that failed to come under control, and the patients eventually died. 2~ Spontaneous resolution has been reported for tumors in the lung and liver in which a biopsy (but no excision) had been performed. 4'2~ Recurrent and large lesions have resolved after radio- therapy. 4,22

Currently, the optimal treatment is complete exci-

758 SCOl-r ET AL

sion, wh ich is usua l ly possible w i t h m i n i m a l morb id i t y .

T h e m a l i g n a n t a p p e a r a n c e of this t u m o r could l ead to

u n n e c e s s a r y r ad i ca l su rge ry or c h e m o t h e r a p y as in our

pa t i en t wi th t he b l adde r lesion. H o w e v e r , a w a r e n e s s o f

this lesion o c c u r r i n g occas iona l ly in ch i ld ren , in a

va r i e ty of sites, shou ld p r o m p t its p rope r iden t i f ica t ion

and t r e a t m e n t .

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