Solitary neurofibroma of the Mesentery: Report of a Case and review of the literature

Solitary neurofibroma of the Mesentery: Report of a Case and review of the literature

PATlIOLOGY RESEARCH AND PRACTICE Tead\ing Ca~ © Urban & Fischer Verlag http://w.m.l.urbanfischer.deJjournalsJprp Solitary Neurofibroma of the Mesen...

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Tead\ing Ca~

© Urban & Fischer Verlag http://w.m.l.urbanfischer.deJjournalsJprp

Solitary Neurofibroma of the Mesentery: Report of a Case and Review of the Literature Gaetano Magro" Maria Piana " Carmelo Venti 2 , Arcangelo Lacagnina 2 and Martino Ruggieri 3 'Institute of Anatomical Pathology and ' Division of Paedriatic Neurology, University of Catania, ' Division of General Surgery, Hospital M. Raimondi, San Cataldo, Ca ltanissetta, Italy

Summary Neurofibromas of the gastrointestinal tract are usually associated with neurofibromatosis type I (Nfl), or they are exelusi ve manifestations of the so-called "familial intestinal neurofibromatosis". Gastrointestinal neurofibromas can rarely occur as sporadic lesions in the jejunum and stomach, and only exceptionally in the mesentery. A critical review of the literature revealed that only seven cases of solitary neurofibromas (SNFs) of the mesentery (six in the ileal mesentery; one in the gastrocolic mesentery) have been reported in patients without stigmata of Nfl. We report the clinicopathologic features of an additional case of SNF of the ileal mesentery, incidentally found in a patient with an ad-

mesentery. To the best of our knowledge, only seven cases of SNF of the mesentery have previously been reported in the literature (Table I). We report an additional case of SNF of the ileal mesentery, review the literature on this topic. and discuss the possible links between this entity and Nfl.

Case Report A 71-year-old man was referred to a hospital elsewhere in Italy because of a 6-month hi story of irrepressible vomiting. Hc was well until first gastrointestinal symptoms appeared. and there was no family history of gastrointestinal diseases or genetic di sorders. Hi s two otherwi s~

vanced gastric carcinoma.

sons were

Since there is increasing evidence that some patients may have some features of Nfl, including dermal or nodular SNFs alone - limited to onc or more body segments - (segmental Nfl), the possibility that SNFs of the mesentery may also represent a segmental manifestation of Nfl is postulated.

remarkable. except for a mass on the left hypogastrium. Endoscopy revealed a pyloric stenosis. Histology of a punch biopsy taken from the gastric wall demonstrated a moderately differentiated adenocarcinoma of the intestinal type. At laparotomy, the posterior gastric wall was stuck to the pancreas. Multiple omental metastatic nodules and a large nodular mass in the ileal mesentery werc observed. A gastric-jejunum anastomosis was performed: peri-pancreatic adipose tissue, two omental nodules and a 15 Clll tract of ileum, including the mesenteric mass, were also excised.

Key words: Solitary neurofibroma - Mesentery - Neurofibromatosis type I

well. General examination was un-

Introduction The term solitary neurofibroma (SNF) refers to a localized neurofibroma occurring in patients without other stigmata of neurofibromatosis type I (Nfl) [3 J. SNF is usually a dermal or nodular skin lesion [3 J that is only rarely found at other sites, including the ileal Pathol. Res. Pract. 196: 7 13-7 18 (2000)

Address for correspondence: Gaetano Magro, Istituto di Anatomia Patologica, Universita' di Catania, Via Bibliotcca 4, 95 124. Catania. Italy. Phone: ++95-310241. Fax: ++95316045. E-mail: magrog.@ 0344-0338/2000/ 196110-713 $15 .00/0

714 . G. Magro el a!. Table I. SNFs of the mesentery reported in the literature Authors

Age (yr)






Leach 1957



Painful mass



Surgical excision


Alive with no recurrence after 7 years

Lahbabi H 1960



Painful mass



Surgical excision

Yannopoulos et al. 1963








Painful mass



Surgical excision

Yannopoulos et a!. 1963 22


Alive with disease

after 1 year

Alive with no recurrence after 11 years

Yannopoulos et a!. 1963



Incidental finding



Surgical excision

Gusarenko et a!. 1978



Painful mass



Surgical excision

Lanzafame et aI. 1994



Painless mass



Surgical excison


Prescnt case



Incidental finding


10 cm

Surgical excison

Died of advanced gastric carcinoma


Alive with no re-

currence after 5 years

Materials and Methods The surgical specimens were fixed in 10% neutrally buffered formalin. Sections were cut and stained with hematoxylin-eosin. van Gieson's for collagen. and Gomori's silver impregnation for reticulin. Immunohistochemistry was performed using a labeled streptavidin-biotin technique (LSAB, Dakopatts) and incubating tissue sections with antibodies to vimentin (mouse monoclonal; prediluted: Immunotech), asmooth muscle actin (mouse monoclonal; dilution 1:500; Dakopaus), desmin (mouse monoclonal; dilution 1:500; DakopaUs), CD34 antigen (mouse monoclonal; prcdiluted; Immunotcch). EMA (epithelial membrane antigen; mouse monoclonal; dilution I: 100; Dakopalts), neuron specific enolase (NSE; mouse monoclonal; prediluted; Immunotech), synaptophysin (mouse monoclonal; dilution: I: I 00; Dakopatts), chromogranin A (mouse monoclonal: dilution: 1.300; Dakopalts), PGP 9.5 (mouse monoclonal; dilution 1:800; Biogenex), c-kit (CDI17; polyclonal antibody; dilution LillO; Biogenex), and S-IOO protein (rabbit polyclonal; dilution 1:800; Dakopalts). Bound peroxidase was visualized using 0.05% 3,3'-diaminobenzidine tetrahydrochloride (Sigma Chemical Co., USA) as a chromogenic substrate for 10 min at room temperature. Negative conlrois excluding primary and secondary antibodies from the staining procedure as well as positive controls were used when appropriate.

Results Pathological findings

The mesenteric mass was well circumscribed, with a smooth surface mcasuring 10.5 x 9.5 x 6.5 Col (Fig. lA). The cut surface rcvealed a firm, solid mass, whitish in color, and confined to the mesentery without involvement of the gut wall (Fig. 1B).

Fig. I. Gross appearence of SNF of the mesentery. A: Uninodular mass with smooth external surface arising from the mesentery. B: The cut surface reveals a firm and solid mass, whitish in color

Solitary Neurofibroma of Ileal Mesentery




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Fig. 2. A: Hypocellular, collagenized spindle cell tumor with pushing borders, B: Bundles of spindly celis scattered among wire-like collagen fibres are typical of neurofibroma. C: Spindle cells showing focal immunoreactivity for S-l OO-protein

716 . G. Magro et al. Histological examination confirmed the metastatic nature of the omental nodules and revealed three lymph node metastases in peri-pancreatic adipose tissue. Notably, the mesenteric mass had the typical morphological features of a collagenized neurofibroma: a well-circumscribed hypocellular tumor (Fig. 2A) composed of wavy bundles of bland-looking spindle-shaped cells, closely associated with wire-like, fibrotic collagen bands (Fig. 2B). Only focally showed the stroma myxoid changes. Cellular pleomorphism and mitoses were absent. The tumor was limited to the mesentery compressing the adjacent gut wall, resulting in an expansive growth pattern. Immunohistochemistry revealed a diffuse positivity for vimentin, while S-IOO protein was detected only focally (Fig. 2C). Staining was negative with all the other antibodies tested. Gross, microscopic and immunohistochemical findings were consistent with the diagnosis of neurofibroma of the mesentery. Follow-up

Soon after surgery, the patient was re-examined, and there were no circumscribed or segmental features of Nfl. Slit-lamp examination revealed no Lisch nodules, and fundoscopy was otherwise normal. Clinical and slit-lamp examinations of both patient's sons were unremarkable. There was no history of neurofibromatosis in any other member of the family. The patient died of cancer-related complications nine months after laparatomy.

Discussion Neurofibromas of the gastrointestinal tract are usually associated with Nfl. Although an old hospital-based series estimated that gastrointestinal neurofibromas occurred in up to 25% of patients with Nfl, the reported frequency is estimated to be around 2.0% or less in most recent population-based studics [6, 11]. These tumors are located in the jejunum followed by the stomach, but multiple sites of involvement as well as unusual locations, including the ileal mesentery, have also been reported {l8J. Visceral neurofibromas are usually situated in the serosa, and some have hyperplasia of Auerbach's plexus, suggesting a disturbance of neuronal proliferation. Only rarely arc neurofibromas limited to the intestine in patients without any other clinical sign of Nfl. Onc possibility is the "familial intestinal neurofibromatosis", a rare dominant disorder, phenotypically distinct from Nfl, and characterized by multiple intestinal neurofibromas restricted only to the intestine {l2, 13J; the other possibility is the sporadic occurrence of multiple or SNFs in patients without any kind of familial neuro-

fibromatosis. In the latter condition, neurofibromas occur primarily in the small bowel, el ss frequently in the large bowel and stomach {l5, 191, and only exceptionally at other sites, including the ileal and gastrocolic mesenteries (Table I). To our knowledge, only seven cases of primary SNFs of the mesentery, all but one occurri ng in the ileal mesentery, have been reported as single case repOtts or as a small series in the literature (Table I). Leach and Vancouver, in 1957 {9J, reported on a giant plexiform neurofibroma of the ileal mesentery in a 22-year-old man who, at the time of diagnosis and after a three year follow-up, had no clinical signs of Nfl. Later, Lahbabi {7 J described an additional case in a 24-year-old man without any clinical sign of Nfl at surgical excision. However, Yannopoulos and Stout {l7 J, reporting their own experience of three well documented eases of mesentery SNFs (Table I), cited hut excluded the two cases mentioned above from the list of the SNF of the mesentery, because in their opinion Nfl could not be completely ruled out, given that cafe' -aulait (CAL) spots appeared seven years after surgical excision, while follow-up data was not available. In the last two decades, knowledge of the natural history and the genetics of the different forms of neurofibromatosis has changed [6, 11- 13/. It is known that there is a 100% penetrance of the Nfl gene (which is located on chromosome 17q 11 .2) by the age of 5 years, and CAL spots in Nfl manifest before the age of two years or not at all {6, 12, 13]. Thus, we believe that the cases of SNF of the ileal mesentery reported by Leach and Vancouver [9 J and Lahbabi [7/ occurred in nonNfl patients, since there were no clinical signs of Nfl at the age of22 and 24 years, respectively. An extensive MEDLINE-based search on SNFs of the mesentery revealed two further cases of SNFs of the ileal mesentery [4, 8/, including one previously reported by one of us (GM) {8J. A review of all the cases recorded in the literature reveals that SNFs of the ileal mesentery may reach a large size (cm 24 in greatest diameter), and that they are usually diagnosed only after histological examination, since, preoperatively, they are interpreted as ovarian cysts or unclassified symptomatic or asymptomatic abdominal masses (Table I). The present case was incidentally found at laparotomy, performed as surgical treatment for an advanced gastric carcinoma. The association between SNF of the ileal mesentery and gastric cancer seems to be incidental, as the literature search revealed no significant coexistence of SNF, irrespective of its location, with malignant epithelial tumors {3, 4, 7-9, 17/. In the present case, the diagnosis of SNF was made on clinical grounds due to the absence of stigmata of Nfl in the patient and lack of Nfl history in the patient's first degree relatives. From the pathological point of view, the differential diagnosis included a wide spectrum of benign spindle

Solitary Neurofibroma of Ileal Mesentery . 717 cell tumor or tumor-like lesions, such as fibromatosis, inflammatory pseudotumor (inflammatory myofibroblastic tumor), solitary fibrous tumor, perincurioma, and the wide spectrum of gastrointestinal stromal tumors (GISTs), including the autonomic nerve tumors (GANTs). Fibromatosis may occur in the mesentery as a sporadic disease or in the context of genetic syndromes, such as Gardner's syndrome [3J. Unlike our case, the peripheral margins of fibromatosis are infiltrating, and it is characterized by a typical growth pattern consisting of interlacing long bundles and fascicles of uniform spindle-shaped cells in parallel array [3]. In addition, immunohistochemistry reveals a variable degree of immunoreactivity for smooth muscle markers (especially a-smooth muscle actin), a tinding that is in line with the myoftbroblastic nature of the cells {3/. Although the inflammatory pseudotumor of the ileal mesentery may present as a uninodular mass and shows a pauciccllular fibroblastic proliferation with prominent hyalinized stroma, it usually contains a conspicuous inflammatory component consisting of lymphocytes, plasma cells and histiocytes [l6J, which is lacking in our casco Furthermorc, the spindlc cells of the inflammatory pseudotumor usually exhibit a myofibroblastic phenotype (variable degree of expression of a-smooth muscle actin and, surprisingly, cytokeratins) [16/. Solitary fibrous tumor is currently considered as a ubiquitous neoplasm arising from the CD34+ interstitial cells of connective tissues [IJ, which may rarely involve the mesentery [5]. Unlike our case, solitary fibrous tumor exhibits a variety of growth patterns, including storiform , hemangiopericytoma-like, and angiofibroma-like patterns; its cellular component is strongly positive for CD34 [I]. Perincurioma is a rare benign spindle cell nerve sheath tumor which may show a variable degree of cellularity and sclerosis. However, it is usually composed of EMA-positive fusiform cells arranged in a fascicular, lamcllar, whorled or storiform pattern /3/. The term GISTs covers a widc morphological and immunophenotypical spectrum of spindly to epithelioid cell neoplasms occurring in the gastrointestinal tract, including the peritoneum, omentum and mesentery [10]. These tumors usually show a higher degree of cellularity than that observed in our case, and most neoplastic cells are immunoreactive for CD 117, CD34. and less frequently exhibit a focal expression of a-smooth muscle actin [10]. Tumors with morphological features overlapping those observed in GISTs, but showing immunohistochemical and ultrastructural features of gastrointestinal autonomic nerve differentiation. are currently termed GANTs [2, 10, 14J. Unlikc neurofibroma, GANTs are usually positive for NSE, synaptophysin, cromogranin A, and PGP 9.5 [2, 14J, although their expression level varies. Notably, the recent literature contains an increasing number of rcports on paticnts having featurcs of Nfl

limited to one or more body segments, the so-called segmental/mosaic Nfl [12, 13]. Its frequency appears to be 1 in 70,000-80,000 or 0.014% [12,13/. Although not proven at the molecular level thus far, somatic mutations of the Nfl gene [12 , 13J are the most likely mechanisms underlying this phenomenon. From the clinical point of view, it is well established that patients with segmental/mosaic Nfl may only have pigmentary anomalies (CAL spots and/or freckling), only neurofibromas (dermal and/or nodular), or only a combination of pigmentary lesions and neurofibromas and plexiform neurofibromas [12, 13 J. Thus, the current opinion that isolated dermal or nodular neurofibromas or isolated plexiform neurofibromas, without any other stigmata of Nfl, occur in circumscribed areas of the body as segmental manifestations of the Nfl, leads to the hypothesis that SNFs of the ileal mesentery could also be an expression of segmental/mosaic Nfl. In conclusion, thc present case, along with those rcpotted previously, supports the possibility that ileal mesentery, although rarely, may be the site of origin of sporadic neurofibromas. Therefore, this tumor should be also considered in the preoperative and intra-operative differential diagnosis of mesenteric masses in patients lacking clinical evidence of Nfl. Finally, we hypothesize that SNFs of the mesentery might be reconsidered and tentatively regarded as mosaic manifestations of the Nfl gene. Acknowledgements. We wish to thank Mrg. Antonella Corsaro for her excellent technical assistance

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