Neurofibromatosis of the Stomach Report

Case Associated with von Recklinghausen's Disease and Review of the Literature

of

a

Victor D. Perea, M.D., New Orleans, and

isolated

A case of neurofibroma of the stomach and mesentery associated with von Recklinghausen's disease and chronic ulcerative colitis in a 44-year-old female is reported. Severe upper abdominal pain, vomiting, and anemia were the most prominent symptoms and all disappeared following subtotal gastrectomy. Review of the English medical literature showed 29 cases of gastric neurofibroma, either single or multiple, 5 of which were also

Ulceration

was was

Report of

'

is

von

or

char¬

an

acterized neurofibromas that arise in the trunks of the spinal, cranial, and sympathetic nerves, usually associated with the presence of cu¬ taneous fibromas, areas of skin pigmentation, ab¬ normalities of the bones, and varying malformities. Nervous system tumors, namely meningiomas,

gliomas, ependymomas, and acoustic neurinomas, are other frequent concomitants; endocrine disor¬ ders and mental deficiency may add to the com¬

plexity of the clinical picture. The histogenesis of the neurofibromas

remains

a

matter of controversy. Virchow called them false neuromas, in the belief that they had a mesodermal

origin,

a

position still ardently defended by

authors, especially ency, however, is

in

some

Europe. The prevailing tend¬

consider the neurofibromas as truly neurogenic neoplasms that originate in the nervous elements of the sheath of Schwann.1'2 Neurofibromas of the stomach may occur as an to

a

Case

A 44-year-old white female was first admitted to St. Joseph's Hospital, Houston, on Sept. 7, 1956 and gave a 3-year history of recurrent episodes of abdominal pain, diarrhea, vomiting, and fever, associated with increasing deterioration and a weight loss of 15 lb. This was diag¬ nosed in 1942 as von Recklinghausen's disease. Her history revealed that she had had an appendectomy in 1928, and a total hysterectomy in 1950. On the basis of the clinical, radiological, and proctosigmoidoscopic findings, a diagnosis of

rather frequent noted in 16 pa-

NEUROFIBROMATOSIS, GENERALIZED Recklinghausen's disease, entity by multiple

manifestation,

up to 1961.

years of age or more; there were 18 females and 11 males. Abdominal pain, anemia, and gastrointestinal bleeding were the most frequent presenting symp-

and a gross lesion tients.

Tex.

or in association with von disease. Recklinghausen's Representative cases, causing varied clinical pictures, have sporadically been reported in the literature. It is the purpose of this report to present 1 case of von Recklinghausen's disease which included involvement of the stomach and mesentery, associated with ulcerative colitis; and subsequently, to discuss in detail the clinical manifestations of 29 cases of gastric neurofibromatosis that were published in the English literature

accompanied by generalized cutaneous neurofibromatosis. All patients were 30

toms.

Lloyd J. Gregory, Jr., M.D., Houston,

From the University of Texas, Post-Graduate School of Medicine, and Clinical Assistant Professor, Baylor University College of Medicine (Dr. Gregory). Dr. Perea is presently Fellow in Nutrition and Metabolism Unit, Department of Medicine, Tulane University School of Medicine.

chronic ulcerative colitis was established. She received treatment, including prednisone, and was discharged after 20 days, much improved. On March 11, 1957, she had to be readmitted because of a violent recurrence of previous symptoms, accompanied by bloody stools. A barium enema examination showed typical ulcerative colitis. She was treated in the same manner, improved, and was discharged on April 3, 1957. In October, 1957, she was admitted to another hospital for treatment of epigastric pain of 2-month's duration.

Although an upper gastrointestinal series was normal it was thought possible that her symptoms were related to a steroid-induced peptic ulcer; accordingly, prednisone ( Meticorten) was stopped and she was placed on an ulcer regi¬ men that was remarkably beneficial. At that time, an

examiner noted the presence of a rather soft, ill-defined mass in the epigastrium. In July and in August, 1958, she was again admitted to St. Joseph's Hospital, due to exacer¬ bations of her ulcerative colitis. By that time, she had developed severe anemia. A gastric analysis showed histamine-resistant achlorhydria. An upper gastrointestinal series on Aug. 1, 1958, showed

irregularity of the greater curvature of the fundus of the stomach of equivocal significance, and a barium enema dem¬ onstrated advanced ulcerative colitis. As a result of increas¬ ing cramping epigastric pain, she was readmitted on March 1, 1959. Another roentgenographic examination of the stomach revealed persistent changes in the greater curvature, but she responded to an ulcer regimen and was released 13 days later. She was admitted to the hos¬ pital for the sixth time, on July 13, 1959, complaining of

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continuous pain across the upper abdomen, that radiated through the back, of 3-weeks" duration. The pain, mostly cramping in character, was aggravated by meals, and for the preceding 3 days had been associated with persistent

vomiting.

Physical examination revealed an emaciated, pale, acutely distressed, white female, who appeared older than her years. Her temperature was 99.4° F. (37.2° C), blood pressure, 120/80 mm. Hg, pulse, 100 beats per minute, respirations,

multiple neurofibromas of the lait spots on the abdomen and the ex¬ tremities. There was marked tenderness and muscle guard¬ ing in the upper abdominal area, and a sausage-shaped, 4 by 2 cm., movable, smooth, firm, tender mass was no¬ ticeable on deep palpation at the level of the umbilicus. The liver and the spleen did not appear to he enlarged. Upper gastrointestinal series again showed abnormal changes in the greater curvature of the stomach ( Fig. 1 ), which were now interpreted as suggestive of either primary neurofibroma of the stomach or secondary involvement by an extrinsic process. An oral cholangiogram failed to visual¬ ize the gallbladder, and a barium enema showed further progression of the ulcerative colitis (Fig. 2). A roentgenogram of the chest, flat films of the abdomen, and an intra¬ venous pyelogram were normal. On July 18, 1959, a gastroscopio examination was done which showed an "elliptical, well-demarcated, gray lesion in the antral portion of the greater curvature, resembling a very shallow ulcer rather than an ulcerated malignant growth." Gastric washing with chymotrypsin was negative for malignant cells, and a gastric analysis again showed histamine-resistant achlorhydria. Examination of the blood revealed a hemoglobin level of 10.6 gm. per 100 ml, a hematocrit of 36%, and a while blood cell count of 23,450, with 70% segmented polymorphonuclear cells, 7% band cells, 3% eosinophils, 6% monoeytes, and 14% lymphocytes. The serum amylase was 117 Somogyi units, and the lipase was 0.3 ml. pel 100 ml. The urea nitrogen level was 10 mg., the fasting blood sugar level 110 mg., and the total protein 6.6 gin.. the albumin 4.5 gm., and the globulin 2.1 gm. per 100 ml. The chloride was 101 per liter. The prothrombin content was 100%. The alkaline phosphatase was 5.9 Bodansky units, and the bromosulfalcin retention was 2.7% at 45 minutes. Examination of the urine was not remarkable. On July 31, during an exploratory operation, the greater curvature of the stomach appeared ulcerated, and infiltrated within an area of 7 em. by 7 cm. It was consider¬ ably thickened and multiple, gray-yellowish, small nodular masses were scattered in the greater and lesser omentum, and a pea-sized tumor was present in the serosa] surface of the descending duodenum. The entire colon was thick¬ ened and edematous. A hemigastrectomy was performed. The patient had a satisfactory postoperative recovery and 24 per minute. She had

skin, and cafe

Fig. 1.—Irregularity of greater curvature of antrum of stomach and hypertrophy of rugae that are suggestive of either primary neurofibroma of the stomach or secondary involvement by an extrinsic process.

au

discharged on Aug. 11, 1959, asymptomatic. pathological diagnoses were: Ulcer on the greater curvature measuring 3 cm. by 2 cm. and lying upon what appeared to be a plexiform neurofibroma (Fig. 3); multiple neurofibromas of the omentum (Fig. 4); and leioinyoma of was

The

the duodenum. Subsequently, the patient's ulcerative colitis flared up and continued to progress. She was then referred to the M. D. Anderson Hospital and Tumor Institutes of Houston, where subtotal colectomy and ileostomy was performed in October, 1960, followed by abdominoperineal resection of the rectum in April, 1961. Repeated gastro¬ scopio examinations and upper gastrointestinal series have failed to show any evidence of recurrent ulcération or neurofibroma of the stomach.

Comment Fig. 2.—Study of colon that shows rigidity, loss of haustral marking, and areas of narrowing consistent with chron¬ ic ulcerative colitis, which has progressed since 1957.

Gastric neurofibromatosis may occur as a solitary or be associated with von Recklinghausen's

tumor

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disease. Its incidence in either case seems to be exceedingly rare. Palmer, in the most extensive survey so far published on this subject3 points out that among 18,276 unselected autopsies, 3 (0.0.6%) benign neurogenic tumors were found, and among 4,806 cases of all types of gastric neoplasms there were

5

(0.10%) benign neurogenic

tumors.

Mar¬

shall quotes only 1 case of neurofibroma in a series of 1,700 gastric tumors removed surgically at the Lahey Clinic over a 25-year period.4,5 As compared to other benign gastric neoplasms, the relative incidence of neurofibromata appears al¬ so to be extremely low. In 1936, Minnes and Gesch¬ ickter0 collected 931 cases from the literature, 102 (10.9%) of which were neurofibromas. In Palmer's study, neurogenic tumors were found to account for 5% of 200 benign nonepithelial tumors of the stomach, but since the benign tumors of epithelial origin were excluded from the total series and schwannomas were included among the neurogenic tumors, the real incidence of gastric neurofibroma presumably was well below 5%. Quite recently, Grafe et al.7 found only 1 neurofibroma in a group of 104 benign tumors of the stomach seen at the New York Hospital from 1952 through March, 1959, a rate slightly less than 1%. Gastric neurofibromas are derived in most in¬ stances from the sympathetic fibers of the subserous mysenteric (Auerbach's) plexus, and less frequently from the submucous (Meissner's) plex¬ us. As noted by Ranks8 it seems likely that the majority of neurofibromas of the stomach remain small and symptomatic throughout life, and may be found accidentally at surgery or autopsy. When they happen to cause symptoms, however, these are far from being scientific or uniform. Our study in¬ dicates that gastric neurofibromatosis may mimic almost every important disease of the stomach, from a bizarre, long-standing functional disorder to

Fig. 3.—Low power of plexiform distribution of periph¬ eral nerves in muscularis of stomach beneath ulcer. Bizarre pattern suggests ramifications of plexiform neurofibroma, but may also be due to intramural neuromas (x 20).

a malignant tumor. Up to 1950, according to Pal¬ mer's review3 41 cases of isolated gastric neurofi¬ bromata were described in the world medical liter¬ ature as well as 28 cases of von Recklinghausen's disease that involved the stomach. Although to some extent this author reviewed the clinical mani¬ festations of the disease, he gave special attention to the study of the gross pathological characteris¬ tics of the lesions themselves.

Reported in the English Literature have attempted to review the clinical aspects

Cases

We of gastric neurofibromatosis. Our study is based on an analysis of 29 case reports which we could col¬ lect from the English medical literature up to 1961. Von Recklinghausen's generalized neurofibroma¬ tosis was present only in 5 patients of this series,9'13 whereas the remaining 24 had isolated gastric neurofibromata. (References concerning these 24 patients are available on request.) Resection was carried out in all 29 patients, thus, in every instance,

Fig. 4.—Low power that shows neurofibroma from gastric omentum. Solid proliferation of schwannian cells has oblit¬ erated architecture of

nerve

(X 20).

the diagnosis was established on the basis of histological examination of the surgical specimen re¬

moved. In 2 patients, however, the neurofibroma was accidentally discovered in the course of ab¬ dominal surgery performed for other diagnosis. Prior to operation, the existence of gastric neuro¬ fibroma was suspected only in 4 patients. In 3 of these,10'12,13 the presence of von Recklinghausen's

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disease assisted in

determining a correct preoperadiagnosis. In the fourth patient, who did not have generalized neurofibromatosis, the possibility tive

of neurofibroma

was

entertained

on

the basis of the

gastroscopic findings. Sex and Age.—In the whole group there were 18 females and 11 males, whose ages ranged from 33

75 years in the former and from 39 to 72 in the latter ( Table 1 ). The average age of males was 52.3 years. This figure agrees with those quoted by Pal¬ mer, and seemingly indicate that clinically gastric neurofibromatosis must be relatively asymptomatic to

Table 1.—Distribution by Age and Sex 1

Females 4*

Totals

.

.

1

8*

9

51-60

.

4*

8*

(¡1-70

.

2* 8

1 2

7 3 5

II

18

29

Ages by Decades 31-40 41-50

More than 70

Males

.

Totals . * One had von Recklinghausen's disease

ä

before the fourth decade of life. The average age of patients with von Recklinghausen's disease did not differ significantly from that of patients with isolated gastric neurofibromata: 50.4 and 52.6 years,

respectively.

Duration of the Disease.—The duration of the disease, from the onset of the symptoms to time of surgery, was variable in 25 patients, symptoms be¬ ing present from 1 week to 25 years (Table 2).

given for 2 patients, and in the accidental operative find¬ ing. Seventeen (70%) of the patients had been sick Duration was not other 2 the tumor

was an

more than 6 months. Nearly one-fourth of the 24 had had distress for 3 months or less, which

for

long-term illness is common, but not at all the rule in neurogenic gastric tumors. suggests

Symptoms and Signs.—The most common symp¬ and signs found in these patients are given in Table 3. Abdominal pain was the leading com¬ plaint of 18 patients; it was referred to the epigas¬ trium in 14, to the left side of the abdomen in 3, and to the right lower quadrant in 1 patient. Pain was variously described as aching, dull, sharp, or cramping, rather continuous, and often aggravated by meals. In only 3 patients did it resemble the hunger pain commonly associated with peptic ultoms

Table

2.—Length of Disease, From Onset of Symptoms to the Time Medical Help Was First Sought Cases with Isolated Gastric

Three months or less. Three to 6 months. Six months to 1 year One to 5 years. More than 5 years. .

ó 2 3

1

8

Disease

1 1

1

.

.

24

5

.

No length of disease given

von

Recklinghausen's

2 2 2

Accidental finding Totals

Cases with

Neurofibromatosis

1

Table Abdominal Anemia

pain

.

Gastrointestinal

Epigastric Vomiting Nausea

3.—Symptoms and Signs

.

mass

bleeding

.

.

.

.

Epigastric discomfort Weight loss Dyspeptic symptoms

.

.

.

Anorexia.

Epigastric tenderness

.

18 15 13

9 9 0

0 6 4 3 2

able to demonstrate any correla¬ pain and the characteristics of the lesion. For instance, at operation large tumors prolapsing into the duodenum were found in 4 pa¬ tients, and 1 of them had never reported pain. Anemia, found in 15 patients, or slightly more than 50% of the cases, was next in frequency. We found that in 11 of these there had been a definite evidence of gastrointestinal bleeding (hematemesis and melena in 6, melena alone in 3, hematemesis alone in 1, and occult blood in the stool of 1 ) and that at operation 9 of them had ulcerated lesions. Although there were no reported manifestations of gastrointestinal bleeding in the remaining 4 pa¬ tients who had anemia, ulcerated neurofibromas were found during surgery in 3 of them. In our case, there was also anemia, and during surgery, an ulcer was found on the greater curvature of the stomach, overlying a plexiform neurofibroma. Thirteen patients (almost 45%) showed signs of gastrointestinal bleeding and of these, 11 had anemia, and 9 had ulcerated neurofibromas at the time of surgery. Four of the 5 patients with von Recklinghausen's disease suffered from anemia, but evidence of gastrointestinal bleeding was present in only 2 (melena in 1, and positive guaiac test in 1). These data indicate that bleeding from the cer. We were not tion between the

a fairly common frequent cause of anemia.

tumor is

occurrence

and the

most

epigastric mass was detected in 9 patients; 1 only of these had generalized disease. It was noticed in our case, also. There was no correlation between this finding and the size of the tumor as found at operation. Vomiting was reported by 9 An

patients, and

by 6;

nausea our case.

also present in

both symptoms were All patients who had le¬

prolapsing into the duodenum did complain of vomiting, but otherwise there was no relation¬ ship between these symptoms and the characteris¬ tics of the gastric lesion. The vomiting was usually postprandial and sporadic, but in a few instances, as in our patient, it was severe enough to become a prominent feature. Six patients complained of some sort of epigas¬ tric discomfort. Thus, a total of 23 patients ( about 80%) of the entire series had either pain or dis¬ comfort over the upper abdomen as one of the main presenting symptoms. Weight loss was not common, but was observed in 6 patients. Even sions

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anorexia which was com¬ of by only 3 patients (10%). Among the patients with generalized neurofibromatosis, only 1 reported weight loss, and none anorexia. Gastric analysis following administration of histamine was done in 7 patients. In 3, no free hydrochloric acid was found, whereas in the other 4, hypocblohydria or normochlorhydria was demonstrated. Results of the roentgenographic examination of the stomach were available for 26 patients. A defi¬ nite tumoral lesion was found in 20, an ulcerated growth in 3, and a plain benign ulcer or crater in 2 patients. Finally, in 1 patient the upper gastro¬ intestinal series was negative. Only 2 patients of the whole series were subjected to gastroscopio examination and in 1 of them the possibility of gastric neurofibroma was raised as result of this study.14 In the other patient, reported by McHardy et al.9 the impression was "predunculated, gray col¬ ap¬

available for 26 patients. The tumors ulcerated in 16, of whom 13 had had a his¬ tory of gastrointestinal bleeding. They were locat¬ ed in the antrum in 12, the fundus in 3, the body of the stomach in 3, the lesser curvature in 4, the greater curvature in 2, the posterior wall in 5, and the anterior wall in 2 patients. Multiple gastric neurofibromas were found in only 3 patients and 2 of them had von Recklinghausen's disease. The size of the lesion ranged from 1.5 cm. to 17 cm. in greatest diameter, and in 4 patients the tumor had prolapsed into the duodenum. A histological diagnosis of neurofibroma was made in 22 patients, and of probable neurofibroma in 7 patients. Among the latter, Schubin and Sar¬ gent described 3 interesting cases,13 whose histo¬ logical structure closely resembled neurofibromas but contained, in addition, inflammatory cell infil¬ tration and marked eosinophils, which suggested a granulomatous element.

Some sort of information about the gross charac¬ teristics of the neurofibromata as found at opera-

Tulane University School of Medicine, 1430 Tulane Ave., New Orleans 12 (Dr. Perea). Dr. Peter Marcuse, Chief, Department of Pathology, St. Joseph's Hospital, Houston, gave valu ihle assistance in the study of this case.

more uncommon was

plained

ored, benign

tumor

polyp."

In

our

patient,

no

parent tumor could be shown on gastroscopio ex¬ amination, but a fair-sized, grayish, superficial ulcer of the greater curvature was found.

tion,

was

were

References 1. Hassin, G. B.: Histopathology of Peripheral and Central Nervous Systems, Hamilton, Ill., Hamilton Press, 1948. 2.

Atlas

Zimmerman, H. M.; Nestky, M. G.; and Davidoff, L. M.: of Tumors of Nervous System, Philadelphia: Lea and

Febiger, 1956. 3. Palmer, E. D.: Benign Intramural Tumors of Stomach: Review with Special Reference to Gross Pathology; Neuogenic Tumors, Medicine 30:116-135, 1951. 4.

Marshall, S. F.: Gastric Tumors Other than CarciReport of Unusual Cases, Surg Clin N Amer 35:693\x=req-\

noma:

702, 1955. 5. Marshall, S. F.: Tumors of Stomach, Surg Clin N Amer 24:607-617, 1944. 6. Minnes, J. F.; and Geschickter, C. F.: Benign Tumors of Stomach, Amer J Cancer 28:136-149, 1936. 7. Grafe, W., et al.: Benign Neoplasms of Stomach, Amer J Surg 100:561-571, 1961. 8. Banks, B. M.: Neurofibroma of Stomach, Gastroenterology 14:158-167, 1950.

9. Browne, D. C.: McHardy, G.; and Mack, S. S.: Gastric Neurofibromas (Case Report) Rev Gastroenterology 16:177-178, 1949. 10. McRobertson, B.: Benign Tumors of Stomach, with Report of 2 Cases, Med J Aust 2:446-448, 1956. 11. Canney, R. L.: Neurogenic Tumors of Stomach, Brit J Surg 36:139-147, 1948. 12. Mimpress, T. W.: Neurofibroma of Stomach in von Recklinghausen's Disease, Case Report, Proc Roy Soc Med 40:120-121, 1945. 13. Schoilldice, E.: Multiple Fibromata Case with Fibroma Enlarging into Stomach, Canad Med Asso 15:66-69,

1925. 14.

Paul, W. D., and Chapman, D. W.: Neurofibroma of Stomach; Gastroscopic Report, Amer J Dig Dis 12:258-260, 1945. 15. Schubin, H., et al.: Gastric Neurofibromas Granulomas, Arch Path 60:286-288, 1955.

TREACHEROUS NEW JERSEY COAST.-While practicing in Ocean County, the doctor (Dr. William Augustus Newell) made professional visits along the Atlantic Ocean and Barnegat Bay. He saw the remains of many ships which had been wrecked along the shores of the treacherous New Jersey coast. The morning after a severe storm, at Barnegat City in 1840, Dr. Newell saw the pathetic wreck of an Austrian brig, the Count Perasto. Eight years later, when serving in the U. S. Congress, the doctor's plan and apparatus, derived from ex¬ perience, provided the impetus for the establishment of a Federal life-saving service

THE

adopted for the entire sea and lake coast line. Indefatigable in this humane Newell in 1848 secured the initial appropriation to establish this life-saving service and later, from 1860-64, served as its superintendent.—F. B. Rogers: HelpBringers: Versatile Physicians of New Jersey, New York, Vantage Press, 1960. that

was

cause,

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Simulating