|LETTER TO THE EDITOR - DOCUMENTING A CASE
|Year : 2011 | Volume
| Issue : 3 | Page : 353-356
Solid alveolar rhabdomyosarcoma with spindle-shaped cells and epithelial differentiation of the mediastinum in a 68-year-old man: A case report and literature review
Yan Qi, Bin Chang, Lijuan Pang, Chunxia Liu, Feng Li
Department of Pathology and The Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Xinjiang, China
|Date of Web Publication||2-Nov-2011|
Department of Pathology, Shihezi University, School of Medicine, Xinjiang - 832 002
|How to cite this article:|
Qi Y, Chang B, Pang L, Liu C, Li F. Solid alveolar rhabdomyosarcoma with spindle-shaped cells and epithelial differentiation of the mediastinum in a 68-year-old man: A case report and literature review. J Can Res Ther 2011;7:353-6
|How to cite this URL:|
Qi Y, Chang B, Pang L, Liu C, Li F. Solid alveolar rhabdomyosarcoma with spindle-shaped cells and epithelial differentiation of the mediastinum in a 68-year-old man: A case report and literature review. J Can Res Ther [serial online] 2011 [cited 2013 Dec 13];7:353-6. Available from: http://www.cancerjournal.net/text.asp?2011/7/3/353/87009
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, and accounts for 4-8% of all malignancies diagnosed in children under the age of 15 years.  Most of the RMSs are located in the head and neck, genitourinary tract, retroperitoneum, upper and lower extremities, but rarely involve the lung, mediastinum or chest wall. Primary RMSs of the mediastinum are rare tumors, histologically most of them are embryonal RMSs, and to our knowledge fewer than 10 cases of alveolar RMS in the mediastinum have been reported so far. ,,,,, Here, we reported one case of solid variant of ARMS with spindle cells and epithelial differentiation, which was confirmed by PAX3-FKHR fusion transcripts and FKHR gene rearrangement detection.
A 68-year-old male presented with right thorax pain and simultaneous cough for 2 months, who subsequently developed dyspnea. Upon X-ray examination, a mass in the right thoracic cavity was found, which was adhered to the pleura [Figure 1]a. Computed tomography (CT) showed a 95 × 94 mm tumor in the right anterior mediastinum with demarcated boundary. Bronchus debouchment of the right superior lobe was compressed and narrowed [Figure 1]b. Surgery showed that the mediastinal tumor was extensively involved in the superior and middle lobes of the right lung, thymus, anterior chest wall and superior vena cava. After surgery, he did not receive further chemotherapy and radiotherapy. Unfortunately, the patient deteriorated with pulmonary metastasis and he died 45 months after the diagnosis.
|Figure 1: (a) Posteroanterior chest radiograph shows a mediastinal contour abnormality. (b) CT scan of the chest showing a 95 × 94 mm tumor in the right anterior mediastinum|
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On sectioning, the mediastinal tumor, measuring 9 × 9 × 4 cm, was tan-red-whitish in color and tended to be soft and fleshy appearance and consistency; foci of hemorrhage and necrosis were seen in some areas. The tumor had directly invaded the right lung, thymus and pleura. Microscopically, the tumor was characterized by solid, infiltrative lesion consisting of predominant spindle-shaped cells [Figure 2]a and epithelioid components [Figure 2]b with extensive necrosis. The former was mainly composed of spindle- or racquet-shaped cells with hyperchromatic nuclei and eosinophilic cytoplasm, frequent arranged in a herringbone growth pattern. Nests of round to oval epithelioid cells with abundant eosinophilic or pale-staining cytoplasm were surrounded by spindle cells and were florid growing near blood vessel. The neoplasm cell exhibited a high rate of mitotic activity (10-15/10 HPF). A transition between the epithelioid and spindle sarcomatous components was seen [Figure 2]c. In addition to the mixture of primitive or undifferentiated cells, scatter or focal neoplastic rhabdomyoblasts with hyperchromatic, eccentrically placed nuclei and ample, brightly eosinophilic cytoplasm were identified [Figure 2]d. Occationally, the nests of round or oval tumor cells with focal necrosis and little fibrosis reminisced about the irregular alveolar-like pattern of RMS.
|Figure 2: Microscopic appearances of the primary tumor. (a) The cells composing most of the tumor are characterized by a cellular proliferation of spindle cells forming long fascicles and often arranged in a herringbone growth pattern (×200). (b) Epithelioid cells showed nested pattern and cytoplasm is abundant and eosinophilic (×200). (c) A transitional region between the epithelioid and spindle sarcomatous components was seen (×400). (d) The main clue for the diagnosis- of rhabdomyosarcoma is the identifi cation of rhabdomyoblasts, which may be spindled/elongated or polygonal (×400)|
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Immunohistochemical studies showed diffuse positive cytoplasmic staining of the tumor cells with vimentin, CD99, NSE, CD34 and cytoplasmic staining with cytokeratin [Figure 3]a, CEA and desmin [Figure 3]b in focal epithelioid cells and few spindle cells. The nuclear expression of MyoD1 [Figure 3]c, myogenin [Figure 3]d were seen in scattered rhabdomyblasts, epithlioid cells and a few spindled tumor cells. The remaining antibodies (SMA, HMB45, S-100, EMA, CD117) were all negative.
|Figure 3: (a) Immunostaining for cytokeratin shows positive cytoplasm in epithelioid cells (Envision method 1:100) ×400. (b) Immunostaining of Desmin, displaying cytoplasm positive (Envision method 1:100) ×200. (c) Immunostaining of MyoD1 displaying positive nuclei (Envision method 1:50) ×400. Immunostaining for myogenin displaying positive nuclei (Envision method 1:25) ×400|
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PAX-FKHR fusion transcripts were detected by RT-PCR. Amplification of a 147-bp fragment of PAX3-FKHR transcript resulting from (2;13) (q35;q14) was positive and confirmed by sequencing in this case [Figure 4]. Dual-color interphase FISH showed that the tumor cell nucleus with the FKHR translocation had one pair of separated green and red FISH signals, while the normal cell nucleus without FKHR translocation had green and red FISH signals in juxtaposition (fusion) [Figure 5].
|Figure 4: Evidence of PAX3-FKHR fusion transcripts by RT-PCR. a, Lane 1, DNA ladder; lane 2, positive sample with PAX3-FKHR fusion transcript (147bp); lane 3, present case with PAX3-FKHR fusion transcript (147bp); lane4, negative sample. b, The PAX3-FKHR transcript breakpoints between PAX3 and FKHR were confi rmed by automated sequencing of the RT-PCR products|
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|Figure 5: Results of hybridization of the Vysis FKHR (13q14) dual color breakpoint probes. The cells of (a) a negative control indicate intact copies of FKHR gene; the alveolar rhabdomyosarcoma case shows one fusion, one orange and one green signal pattern indicative of a rearrangement of one copy of the FKHR gene region (b)|
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RMSs can be subdivided into three variants according to the histological and genetic features: embryonal, alveolar and pleomorphic RMS. Cases in which the alveolar pattern is poorly developed are referred to as the "solid" variant of ARMS and are particularly difficult to diagnose. Cytogenetic and molecular biological studies have revealed that about 70%-90% of ARMSs have specific chromosomal translocations t (2;13)(q35;q14) and t (1;13)(p36;q14) resulting in the fusion transcripts PAX3-FKHR and PAX7-FKHR, respectively, and play a critical role in the diagnosis of ARMS.
RMSs may occur at any site, but primary tumors are more commonly located in head and neck (42%), urogenital tract (34%), and extremities (11%). Alveolar tumors tend to occur primarily in the trunk and extremities, whereas embryonal tumors are more often found in the head and neck or genitourinary and paratesticular sites. Primary RMSs of the mediastinum are rare tumors and often associated with germ cell, teratomatous or malignant epithelial components. , Previously, there had been about 20 reports that described mediastinal RMSs, most of these which were embryonal or pleomorphic RMSs, fewer than 10 cases were alveolar RMSs, and only the four cases of solid variant ARMS, ,, were composed of small round cells or undifferentiated tumor cells without epithelial or spindle cell differentiation described. We present here, for the first time, one case of solid variant of ARMS composed of predominant spindle sarcomatous cells and epithelioid components with focal rhabdomyoblastic differentiation in the mediastinum in a 68-year-old man, which was confirmed by PAX3-FKHR fusion transcripts and FKHR gene rearrangement detection.
Tumors of the mediastinum represent a wide diversity of disease states. The diagnosis of RMS is established only after sarcoma-like primary lung malignancies and metastatic disease have been excluded. The clinical presentations and imaging findings are not characteristic for the tumors classification. Morphology and immunohistochemistry are helpful for recognizing RMS. Histologically, the main clue for the diagnosis of RMS is the identification of plump spindle or polygonal-shaped rhabdomyoblasts with abundant eosinophilic cytoplasm and hyperchromatic, eccentrically placed enlarged nuclei. Immunophenotypic markers such as myogenin, MyoD1, desmin, and sarcomeric actin were very useful for diagnosis of RMSs. However, mediastinal ARMS, especially the solid form of this tumor that lack an alveolar pattern entirely and are composed of densely packed groups or masses of tumor cells resembling the round cell areas of embryonal RMS or with epithelial differentiation and spindle cells should be distinguished from the other RMS subtypes (such as spindle cell RMS), and includes a variety of other sarcomas which are synovial sarcoma, Ewing's sarcoma, and poorly differentiated carcinosarcoma, germ cell tumors with rhabdomyosarcomaous differentiation and malignant peripheral nerve sheath tumors (malignant Triton tumor). Accurate diagnosis can now be aided by identifying specific genotypic criteria using cytogenetics, interphase fluorescence in situ hybridization and reverse transcription PCR for detection of PAX3-FKHR fusion transcripts and FKHR gene rearrangement.
Little is known about the mechanism of epithelial differentiation in RMSs. Churg  (1978) proposed that the commonly believed correspondence of ARMS to the myotube stage of muscle differentiation is incorrect; if anything, the overall pattern of the tumor is epithelioid, and may correspond to the organization of mesenchymal cells at the stage of somite differentiation. In our case, electron micrographs showed primitive mesenchymal cells located in the region where positive staining of cytokeratin and MyoD1 occurred. Therefore we suppose that the epithelial component in ARMS was derived from the sarcomatous component through the function of differentiation of mesenchymal stem cells, which may be caused by abnormal expression of Pax3.
| > Acknowledgments|| |
We sincerely thank Dr. Yanfeng Zhong for technical assistance with the electronic microscope, Professor Tiancai Lu and Wenhao Hu for helpful discussions and pathological review of the clinical cases and Dr. Philip Allen for diagnostic guidance.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]