|
Indian Journal of Surgery
Medknow Publications on behalf of Association of Surgeons of India
ISSN: 0972-2068
Vol. 66, Num. 2, 2004, pp. 108-110
|
Indian Journal of Surgery, Vol. 66, No. 2, Mar-Apr, 2004, pp. 108-110
Case Report
Malignant gastrointestinal stromal tumor (neural type)
of the rectum
S. Devaji Rao, J. Vijayan, A. Chandrasekhar Rao, R. Sridhar, Mitra Ghosh*
St. Isabel's Hospital, Oliver Road, Mylapore, Chennai - 600004, India; *Apollo
Speciality Hospital, Nandanam, Chennai - 600035, India.
Address for
correspondence: Dr. S. Devaji Rao, Dhanwanthri Surgical Clinic, 15, Vinayagam
Street, Somu colony, Chennai -
600028, India.
Paper Received: September 2002. Paper Accepted: January 2003. Source
of Support: Nil.
Code Number: is04027
ABSTRACT
Gastrointestinal stromal tumor is a rare but a new clinical
entity. In the gastrointestinal tract it occurs least in the rectum. This tumor
is resistant to chemoradiation and adequate surgical resection is the only
definitive treatment.
Key words
Stromal tumor, Malignant, Rectum, Neural type.
How to cite this article: Rao SD, Vijayan J, Rao AC, Sridhar R, Ghosh
M. Malignant gastrointestinal stromal tumor (neural type) of the rectum. Indian
J Surg 2004;66:108-10.
INTRODUCTION
Stromal tumors of the gastrointestinal tract are rare neoplasms
accounting for <1% of all GI malignancies.
They were thought to arise from the muscular layer of hollow
organs and their presumed origin from smooth muscle cells has led to the use
of terms such
as `leiomyoma', `leiomyoblastoma' and `epitheloid
leiomyosarcoma'. Unfortunately, the exact origin
of these tumors is difficult to determine
microscopically. The histogenesis, classification, diagnostic criteria
and biological behaviour of these tumors have been
subject to much controversy, and the non-specific
term gastrointestinal stromal tumor (GIST) has been
coined. It has become clear that GISTs show remarkable
cellular variability and histology that GIST cells may be able
to differentiate towards a variety of cell types or
may remain undifferentiated. Immunohistochemistry
and electron microscopy have shown GISTs to have myogenic features (smooth muscle
GIST), neural attributes (neural GIST), both smooth muscle and
neural attributes (mixed GIST) and lack of any
differentiation. Very recently, a relationship of GISTs to the
interstitial cells of Cajal, a complex cellular network within
the muscle wall of the gut where they function as
a muscular pacemaker system controlling gut
motility1 has been proposed. They seem to be resistant to chemoradiation
and have a very high potential to recur. Two thirds of GISTs arise from the stomach,
25% from the small bowel (one third in the duodenum), and less than 10% in colorectal
regions. Rectal GISTs are extremely rare. This paper reports a case of malignant
neural type of a GIST of the rectum, in a young patient.
CASE REPORT
A 34-year-old male presented with bleeding per rectum, pain
during defecation and evening rise of fever with mild rigor for 6 months' duration.
The pain was dull and constant. He complained of loss of appetite and weight.
On examination, the general physical examination was normal. Examination of
abdomen was also normal with no hepatosplenomegaly. Proctoscopy revealed second
degree hemorrhoids. Digital examination of the rectum revealed a soft swelling
touching the examining finger. A clinical diagnosis of carcinoma of the rectum
was made. Colonoscopy revealed a large friable growth in the rectum about 5cm
from the anal verge. Biopsy of the lesion suggested undifferentiated adenocarcinoma
probably of the signet cell variety. All the investigations, like the blood
biochemistry, liver function tests, chest radiography and the abdominal ultrasonography
were normal.
Low anterior resection of the rectum with EEA stapling was
done. The patient had an uneventful post - operative recovery. The cut specimen
of rectum revealed a soft polypoidal growth measuring 5 x 4 x 4 cm projecting
into the lumen. The histopathology of the tumor showed sheets of neoplastic
spindle - shaped cells with oval to elongated vesicular nuclei, prominent
nucleoli with eosinophilic cytoplasm. Numerous
mitotic figures (12 - 15 / 10 HPF) were seen. The tumor
was ulcerated in areas and covered by granulation
tissue. The neoplastic cells showed strong positivity
with Vimentin and S 100 protein and were negative
for Cytokeratin, LCA, Desmin, CD 34 and HMB - 45.
The origin of the tumor was from the region of
muscularis mucosae. The muscularis propria at the base was
not infiltrated. 3 / 7 lymph nodes were positive for
tumor and the resected margins were free of tumor.
A final diagnosis of high grade, malignant gastrointestinal
stromal tumor of the rectum (neural type) with lymph node metastases was
made, based on the tumor marker study and negativity of CD34.
The patient was followed up for over 24 months and he continues
to be asymptomatic and healthy.
DISCUSSION
Gastrointestinal stromal tumors (GISTs) are the most common
mesenchymal tumors of the gastrointestinal tract, but they are rare in occurrence.
Majority of patients present in the fifth to the seventh decade of life with
male predominance (2:1). They are most common in the stomach (70%), followed
by small intestine (20%), colon and rectum (5%) and oesophagus (<5%).
GISTs may range in size from few millimeters to over 30 cm,
however, size alone does not predict biologic behavior with certainty. Symptoms
usually depend on the tumor size and location but many are asymptomatic, and
the tumors are often discovered incidentally during laparotomy for other conditions
and they are more benign in variety. Most patients with malignant stromal tumors
are symptomatic, the most common being abdominal mass closely followed by GI
bleeding as a result of overlying mucosal ulceration and pain. The remainder
of the symptoms may include anorexia, dysphagia, obstruction, perforation,
or fever. Tumor in the stomach and small intestine commonly present with bleeding.
In the oesophagus, the first manifestation may be obstruction, dysphagia and
in the rectum, bleeding, obstruction and altered bowel habits. Occasionally,
duodenal GISTs may cause obstructive jaundice. GISTs are characteristically
well circumscribed and may grow in an endophytic fashion and potentially compromise
bowel lumen patency. Malignant GIST tumors occur with increasing frequency
in the distal small bowel.
The malignant potential of these tumors are best
estimated by the simultaneous evaluation of
several clinical parameters such as size, location in the
gut, invasion of the adjacent organ, mucosal
invasion, degree of cellularity, cellular architecture, mitotic
count, nuclear polymorphism, necrosis and proliferation
rate.2 Since within a tumor, there may be considerable heterogeneity
with respect to those features that separate benign tumors from malignant ones,
thorough sampling for microscopic evaluation is essential, for precise diagnosis.
A minimum of one tissue
section per centimeter of tumor diameter is required.
At laparotomy, the only absolute criterion of malignancy is
the spread beyond the organ of origin at the time of diagnosis, but mucosal
ulcer over the tumor is considered a sign of malignancy. Those tumors are locally
confined at diagnosis and found incidentally during surgery generally behave
in a benign fashion. However, resection of these tumors is necessary, since
their behavior is unpredictable and they have to be pathologically examined.
Radiation therapy and chemotherapy have been used to a lesser extent, mainly
in a palliative setting. Neither modality has been shown to be particularly
effective because these tumors seem to be resistant to chemoradiation.
In recurrent tumors, surgery should be reserved largely for
symptom control, since disease specific survival seems to be determined by
the biology and size of the primary tumor.
T 1571 (Glivec) a potent tyrosine kinase inhibitor which is
also a potent inhibitor of C Kit has shown good tolerance and appreciable anti-tumor
activity in the GIST.3 This drug has been used in doses of 400 to
4000 mg daily with good results.
Hurlimann et al4 observed smooth muscle differentiation
in 30% of the cases, neural differentiation is 10%, dual smooth muscle and
neural differentiation in 3% and no obvious differentiation in 40%. In tumors
with neural differentiation, Vimentin is expressed
in 95% of tumors, Neuron specific enolase in 50 - 100 %, Synaptophysin in
100%, Neurofilament protein in 10%, S-100 in 20 - 60%, Vasointestinal peptide
in 20 - 40% and CD 34 in 60%. Tumors with smooth muscle differentiation, do not
express Neuron specific enolase, Synaptophysin, Chromogranin, Glial fibrillary
acidic protein, or Protein gene product 9.5 but express lineage specific markers,
like Muscle specific antigen (HHF - 35) in 68%, Smooth muscle actin (SMA) in
57% and Desmin upto 50%.
A type of GIST showing neural differentiation is the gastrointestinal
autonomic nerve tumor (GANT), which are uncommon stromal tumors with morphological
features resembling the cell processes of the enteric autonomic plexus that
occasionally develops in the context of von Recklinghausen's disease. GANTs
are typically epitheloid or spindle celled and usually of low histological
grade.5 They typically express S-100, Neuron specific enolase, Vimentin
and Synaptophysin and they are CD 34 negative, as in the present case. GANTs
can be distinguished from other GISTs only on the basis of their unique ultrastructural
features.
REFERENCES
- Ward SM, Burns AJ, Torihashi S, Sanders KM. Mutation of
proto-oncogene c-kit blocks development of interstitial cells
and electrical rhythmicity in murine intestine. J Physiol 1994;480:
91-7.
- Miettinen M, Sarlomo-Rikala M, Lasota J. Gastrointestinal
stromal tumors: recent advances in understanding of their biology. Hum
Pathol 1999;30:1213-20.
- Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford
JM, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine
kinase in chronic myeloid leukemia. N Eng J Med 2001;344: 1031-7.
- Hurlimann J, Gardiol D. Gastrointestinal stromal tumours:
An immunohistochemical study of 165 cases. Histopathology 1991;19: 311-20.
- Matsumoto K, Min W, Yamada N, Asano G. Gastrointestinal
autonomic nerve tumors: immunohistochemical and ultrastructural studies
in cases of gastrointestinal stromal tumor. Pathol Int 1997;47:308-14.
© 2004 Indian Journal of Surgery.
|