Clear Cell Sarcoma

What is clear cell sarcoma?

Clear cell sarcoma is a rarely occurring soft tissue malignancy with a chromosomal translocation, t(12;22)(q13;q12), or a consequential EWSR1-ATF1 combination of gene.

Furthermore, the cancerous growth developing in the GI tract may have a variation of combination gene including EWSR1-CREB1. The clinical presentation is quite similar as soft tissue sarcoma or melanoma, like melanocytic differentiation, but the genetic event is unique in clear cell carcinoma.

Similar to soft tissue sarcomas, Clear cell sarcoma also has a tendency to primarily develop in the deep soft tissue, without skin invasion, and has priority for pulmonary or lymph node metastasis.

Clear cell carcinoma is more prevalent in white skinned North American in comparison with black or fair skinned African Americans or Asians without having any gender specification.

The clear cell sarcoma can develop in childhood to in older age (the range of age limit mostly stands between 7 – 83 years, mean age is 27 years of age). Only 2% incidence rate is predominantly occurring in kids less older than 10 years. ^(1,2)

Symptoms & Signs

1. Very minimal, almost 1% involvement is related to the soft tissue tumors. The size of the tumor of the clear cell sarcoma is less than 5 cm, but have tendency to invade deep tissue and lesion may extend from juxtaposed to fascia, tendons, or aponeuroses.
2. The mostly affected sites are ankle and foot; other involved sites are the bones, male genital organ, kidney, gastrointestinal tract and other abdominal organ covered anterior side with a peritoneum layer (retroperitoneum).
3. The primary location of the Clear cell sarcoma is in the skeleton system and tumors are metastatic in nature. The clinical presentation of clear cell sarcoma and melanoma is so similar that this often creates diagnostic confrontation.

Diagnosis

Imaging findings

Different imaging technologies like radiographs, computed tomography and magnetic resonance helps to identify the specific signs of clear cell sarcoma, which include rare findings of calcifications inside the tumor, the tumor is shaped as distinct homogenous mass, similar color intensity (isointense) or mild lighter color than the surrounding tissue (hyperintense)identified in the muscle. In some cases, foci of hypointensity may occur, equivalent to melanin. ^(1,2)

Laboratory findings

Clear cell carcinoma is looked like a tan-gray, solid, confined mass in naked eye. Under the microscope, the tumor is extremely indistinguishable and arbitrarily structured. Dissection of the tumor shows, presence of fascia,  intense fibrous connective tissue of tendons, and aponeuroses.

The clear cell manifestation is due to the amassing of glycogen. The nature of metastasis or growth rate of the tumor occurs in slow-growing manners. Extended multi-nucleated gigantic cell masses are usually present; some distinct necrotic tissue areas and pigmentation with melanin may be detected.

Cytological findings

Approximately 90% of clear cell sarcoma cases identify the mutual translocation of t(12;22)(q13;q12). Repeal transcriptase polymerase chain reaction (RT-PCR), and fluorescent in situ hybridization (FISH) is identified in chromosome analysis.

EWSR1/ATF1 fusion and EWSR1/CREB1 fusion are responsible for the translocation t(2;22)(q32.3;q12). Current evidence revealed that the fusion protein of EWSR1/ATF1 is competent of attaching to and trigger the melanocyte-specific microphthalmia-associated transcription factor (MiTF), in the existence of the sox10 transcription factor, consequences in appearance of the melanocytic phenotype and control the development/endurance of clear cell sarcoma cells. ^(1,2,3,4)

Treatment

Surgical intervention

Traditionally surgical resection is often used to correct the clear cell carcinoma. If whole tumor growth can be rectified by surgical removal, then usually adjuvant treatments are not required.

Sometimes amputation of limbs may need to proceed, because of the vascular or neural involvement. In marginal or intralesional expurgation recurrence rate is high, therefore adjuvant radiation therapy is referred to recover local tumor progression.

The different chemotherapueutic agent may be prescribed to control the metastasis, cisplatin alone or combination therapy like cisplatin with caffeine-assisted chemotherapy or doxorubicin with caffeine-assisted chemotherapy may obtain a tumor reaction.

Single doxorubicin chemotherapeutic agents unable to bring effective response against tumor metastasis. Some cases, injection of interferon alpha 2B is given via intralesional and effective result is obtained.

Extension of regional metastasis often involve lymph node and affect distant organs including bones and lungs. Sometime lymphadenectomy is also applied, though the effectiveness is unclear. It is always advisable to recommend lymphadenectomy after confirmation of the specific regional lymph node participation through cytological investigation and fine needle aspiration (FNA) methods.

Lymphoscintigraphy and blue dye application is usually applied for lymphatic mapping and SLNB (sentinel lymph node biopsy) assisting in guiding the stage of advancement of regional extension of metastasis and directing the scope of surgery and choice for adjuvant therapy. ^(1,2,3,4)

Prognosis

The survival rate of clear cell sarcoma at the early age of onset, including 5, 10 and 20 years has an extended from 67% to 10%. In these cases the recurrence rate is high, almost 84%. At the 29 years age metastasis may diagnose.

The effectiveness of the treatment and outcome of the therapy depends upon tumor size, location, DNA content, mitoses, necrosis, and resection margins.

Usually less than 5cm size of the tumor is not metastatic in nature or recurrence rate is rare, whereas more than 5cm tumor has metastasis property. Involvement of the lymph node has pitiable prognosis. ⁽²⁾

References

1. Hisaoka M, Ishida T, Kuo TT, Matsuyama A, Imamura T, Nishida K, Kuroda H, Inayama Y, Oshiro H, Kobayashi H, Nakajima T, Fukuda T, Ae K, Hashimoto H.; Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases; Am J Surg Pathol. 2008 Mar;32(3):452-60. doi: 10.1097/PAS.0b013e31814b18fb; Retrieve from: http://www.ncbi.nlm.nih.gov/pubmed/18300804

2. AF Mavrogenis, G Bianchi, NA Stavropoulos, PJ Papagelopoulos, and P Ruggieri ; Clinicopathological features, diagnosis and treatment of clear cell sarcoma/melanoma of soft parts; Hippokratia. 2013 Oct-Dec; 17(4): 298–302. Retrieve from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097407/

3. Nirupma Lal and Atin Singhai; Clear cell sarcoma of kidney: A rare entity; Indian J Med Paediatr Oncol. 2011 Jul-Sep; 32(3): 157–159.; doi: 10.4103/0971-5851.92817; Retrieve from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342723/

4. O. Hocar, A. Le Cesne, S. Berissi, P. Terrier, S. Bonvalot, D. Vanel, A. Auperin, C. Le Pechoux, B. Bui, J. M. Coindre, and C. Robert; Clear Cell Sarcoma (Malignant Melanoma) of Soft Parts: A Clinicopathologic Study of 52 Cases; Dermatology Research and Practice; Volume 2012 (2012), Article ID 984096, 8 pages; Retrieve from: http://www.hindawi.com/journals/drp/2012/984096/

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