Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT) is a rare malignant neoplasm arising within the wall of the small bowel, stomach, or large bowel, predominantly in children and young adults. It is an aggressive tumor with a high rate of local recurrence, metastases, and early death from disease. Histologically, it is composed of relatively monomorphic ovoid or round cells with clear to eosinophilic cytoplasm, arranged in sheets and sometimes papillary or alveolar architectures, often with CD68-positive osteoclast-like giant cells in variable numbers, and is associated with
Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT) is a rare malignant neoplasm arising within the wall of the small bowel, stomach, or large bowel, predominantly in children and young adults. It is associated with high rates of local recurrence, metastasis, and early deaths from disease. Histologically it consists of relatively monomorphic ovoid or epithelioid cells with clear to eosinophilic cytoplasm arranged in sheets and papillary or alveolar architectures, with variable numbers of CD68-positive osteoclast-like giant cells. Because of the nonspecific immunoprofile of focal S100 protein expression and general lack of immunoreactivity to other antibodies, it may be misdiagnosed as a variety of neoplasms, including melanoma, malignant peripheral nerve sheath tumor, or gastrointestinal stromal tumor (GIST). We describe a case arising in the small bowel wall and harboring
A 33-year-old Caucasian male presented to the Emergency Department of his local hospital with worsening abdominal pain, exacerbated by eating, which he had had intermittently for the preceding five months and which had led to weight loss of two stone over the last three months. On clinical examination, the patient had abdominal distension and pain in the lower right quadrant, along with high pitched bowel sounds. 20 years previously, at the age of 13, he had been treated for hepatoblastoma with six cycles of PLADO regimen (cisplatin and doxorubicin) chemotherapy followed by partial hepatectomy and radiotherapy in the context of a Society of Pediatric Oncology Liver Cancer (SIOPEL) Group clinical trial. He had been fit and well since, without detectable late effects from this regimen. The patient’s father and grandmother had both been previously successfully treated for colon cancer in their 60s, but there was no other family history of cancer. Abdominal X-ray showed prominent small bowel loops and no air in the rectum. Abdominal computed tomography (CT) scan revealed distal small bowel obstruction due to an intussusception in the right lower quadrant of the abdomen. A 3 cm mass was present at the apex of the intussusception, along with two enlarged mesenteric lymph nodes. The imaging also showed features relating to the patient’s previous treatment, with extensive metallic artefact deep into the liver, abutting a patent portal vein with an unusual course of marked anterior looping, a very small pancreatic head and neck, and absent gallbladder, with clips around the portal vein at the head of the pancreas. No focal abnormalities were seen within the liver or spleen. The small bowel mass was resected with clear margins and a primary anastomosis formed. The patient made a good recovery and was discharged shortly afterwards, and owing to the local hospital diagnosis of gastrointestinal stromal tumor (GIST) he was referred to our tertiary center. The diagnosis was revised to clear cell sarcoma-like tumor of gastrointestinal tract, as below. Given the absence of residual disease and the largely resistant nature of this neoplasm to standard chemotherapeutic regimens, there was no role for adjuvant chemotherapy, and hence the treatment plan was for close clinical and radiological followup. Two months later, the patient was admitted to his local hospital with a two-week history of fevers with night sweats and rigors. No specific source of infection was noted clinically, but ultrasound scan of the abdomen showed abnormal liver lesions which were thought to represent possible abscesses. Treatment with intravenous metronidazole and tazocin was commenced for pyrexia of unknown origin and he was again referred to our institution. CT scan showed rapid progression of locally recurrent disease with the development of peritoneal nodules, widespread liver metastases, and prominent mesenteric adenopathy. The liver was biopsied and showed metastatic tumor with similar morphology and immunoprofile to that in the small bowel. Owing to the rapid disease progression, the patient did not wish to be considered for systemic therapy and died from advanced malignancy seven months after initial presentation with this neoplasm.
The histopathological features were noted, and a comprehensive immunohistochemical panel was applied (antibody dilutions and sources are in Table
Antibodies used for immunohistochemistry.
Antibody | Source | Dilution |
---|---|---|
AE1/AE3 | Zymed Laboratories, CA, USA. | 1 : 50 |
MNF116 | Dako, Glostrup, Denmark. | 1 : 400 |
Cam5.2 | Becton Dickinson, Plymouth, UK. | 1 : 10 |
EMA | Dako, Glostrup, Denmark. | 1 : 400 |
Desmin | Dako, Glostrup, Denmark. | 1 : 50 |
SMA | Dako, Glostrup, Denmark. | 1 : 200 |
S100 protein | Dako, Glostrup, Denmark. | 1 : 1500 |
HMB45 | Dako, Glostrup, Denmark. | 1 : 100 |
MelanA | Dako, Glostrup, Denmark. | 1 : 25 |
CD34 | Novocastra Laboratories, Newcastle upon Tyne, UK. | 1 : 30 |
CD45 | Dako, Glostrup, Denmark. | 1 : 20 |
CD56 | Invitrogen, Camarillo, CA, USA. | 1 : 50 |
CD117 | Dako, Glostrup, Denmark. | 1 : 500 |
DOG1 | Novocastra Laboratories, Newcastle upon Tyne, UK. | 1 : 50 |
Chromogranin | Dako, Glostrup, Denmark. | 1 : 300 |
GFAP | Dako, Glostrup, Denmark. | 1 : 200 |
Neurofilament | Dako, Glostrup, Denmark. | 1 : 200 |
NSE | Dako, Glostrup, Denmark. | 1 : 600 |
Synaptophysin | Dako, Glostrup, Denmark. | 1 : 100 |
INI1 | Becton Dickinson, Plymouth, UK. | 1 : 100 |
MIB1 | Dako, Glostrup, Denmark. | 1 : 100 |
Grossly, the specimen consisted of two segments of small intestine, the larger approximately 30 cm in length with attached omentum. 14 cm from one margin there was a polypoid 4 cm diameter tumor obstructing the lumen. The serosa was unremarkable, as was the smaller piece of bowel. Histologically, the mass was an ulcerated polypoid infiltrative hypercellular neoplasm involving the full thickness of the small bowel wall (Figure
(a) Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT). Low power view shows diffuse infiltration of the wall of the small bowel completely destroying the muscularis propria and with obliteration of the intestinal mucosa leaving just a thin strip of epithelium overlying each of the villi. (b) The tumor comprises sheets and vague nests of epithelioid or ovoid cells which show moderate nuclear atypia and amphophilic or clear cytoplasm. The nests are much more ill defined than those seen in conventional soft tissue clear cell sarcoma of tendons and aponeuroses. (c) At higher power, the cells show medium sized ovoid to occasionally spindled vesicular nuclei and often small nucleoli. There are prominent mitotic figures. Here, the cells are present in a diffuse sheet-like pattern without discernible nested architecture. (d) There is diffuse nuclear and cytoplasmic expression of S100 protein. S100 protein expression without staining for melanocytic markers is typical of CCSLGT, although some cases may show patchier S100 protein immunoreactivity. Note the diffuse infiltration of the small bowel muscularis propria and tumor proximity to serosal fat. (e) Metastatic CCSLGT in the patient’s subsequent liver biopsy. The metastatic tumor has similar morphology, although it contains cells with amphophilic cytoplasm and no clear cytoplasm or any nested pattern. The lack of characteristic cytologic or immunophenotypic features and the lack of familiarity of pathologists with this neoplasm can understandably lead to confusion with other metastatic tumors with epithelioid or ovoid cell morphology. (f) Diffuse S100 protein expression is also present in the liver metastasis.
The tumor was strongly and diffusely positive for S100 protein (Figure
The core biopsies from the liver showed moderately congested and chronically inflamed liver parenchyma containing cellular tumor comprising sheets and vague nests of uniform epithelioid cells with hyperchromatic ovoid nuclei, moderate amounts of amphophilic cytoplasm (Figure
We describe a case of clear cell sarcoma-like tumor of the gastrointestinal tract, arising in the small bowel of an adult male, which harbored
CCSLGT was first described by Zambrano et al. in 2003 [
This study describes a molecularly confirmed CCSLGT, with
Given the rarity of this neoplasm and the fact that it can easily mimic more common lesions occurring at intra-abdominal sites including conventional CCS, metastatic melanoma, GIST, malignant perivascular epithelioid cell neoplasm (PEComa), and clear cell carcinomas such as those from the kidney, it seems likely that the true incidence of CCSLGT is underrepresented because it has been misdiagnosed due to unfamiliarity of surgical pathologists with the entity and the largely nonspecific immunophenotype.
In summary, we report a case of CCSLGT, which occurred as a second malignant neoplasm in a 33-year-old male who had had previous chemotherapy and irradiation for childhood hepatoblastoma. The etiology of these rare and largely rapidly fatal neoplasms remains unknown, and this report draws further attention to childhood irradiation as a possible precipitating factor. It remains to be seen whether CCSLGT will emerge as a potential late complication of the presumed irradiation component of the treatment for hepatoblastoma or other pediatric neoplasms or whether this case simply represents an unrelated second malignancy in a patient who had increased susceptibility to neoplasia compared to the general population. Documentation of any CCSLGT is nevertheless important due to its extreme rarity, particularly when occurring in patients with relevant past medical histories, so that we can come closer to establishing its cause. While effective treatments are not yet available for this highly aggressive neoplasm, future targeted therapies that inhibit the function of the
The authors have no conflict of interests or funding to disclose.
The authors are grateful to Drs. David Gonzalez and Lisa Thompson and Mrs. Dorte Wren (Molecular Diagnostics, Royal Marsden Hospital and The Institute of Cancer Research, Sutton, Surrey) for carrying out RT-PCR and Mr. John Swansbury and Dr. Toon Min (Haematology Cytogenetics, Royal Marsden Hospital and The Institute of Cancer Research, Sutton, Surrey) for FISH studies. They acknowledge support from the NIHR RM/ICR Biomedical Research Centre.