Med Mol Morphol DOI 10.1007/s00795-015-0108-1
CASE REPORT
Paratesticular dedifferentiated liposarcoma with prominent myxoid stroma: report of a case and review of the literature Shogo Tajima1 • Kenji Koda2
Received: 31 March 2015 / Accepted: 8 May 2015 Ó The Japanese Society for Clinical Molecular Morphology 2015
Abstract Paratesticular sarcoma is rare, but liposarcoma is its most common type. Paratesticular liposarcoma sometimes presents as dedifferentiated liposarcoma. Both high-grade and low-grade dedifferentiation have been reported. Herein, we presented a unique case of a 64-year-old man with low-grade dedifferentiated liposarcoma with prominent myxoid stroma. Well-differentiated liposarcoma components extended along the spermatic cord. The constituent cells of the dedifferentiated component were peculiar in that, they were relatively uniform cells with atypia and did not have pleomorphism to such an extent that it mimicked myxofibrosarcoma. This myxoid component was confidently differentiated from myxoid liposarcoma with the help of immunohistochemical analysis using CDK4 and MDM2. These two markers were also expressed in the well-differentiated component. It could therefore be confirmed that this sarcoma is dedifferentiated liposarcoma but is not mixed-type liposarcoma comprising well-differentiated liposarcoma and myxoid liposarcoma.
& Shogo Tajima [email protected] 1
Department of Pathology, Shizuoka Saiseikai General Hospital, 1-1-1 Oshika, Suruga-ku, Shizuoka 422-8021, Japan
2
Department of Pathology, Fujieda Municipal General Hospital, Shizuoka, Japan
Keywords Spermatic cord Paratesticular liposarcoma Dedifferentiated liposarcoma Myxoid stroma CDK4 MDM2
Introduction Paratesticular tumors account for 2–3 % of all scrotal tumors. They originate from the spermatic cord, testicular tunica, or epididymis [1–4]. Paratesticular liposarcomas had been reported as single case studies or as components of larger series, until Montgomery et al. reported 30 paratesticular LPSs [5]. Among them, 19 cases were of well-differentiated liposarcoma (WDL), and 10 cases were of dedifferentiated liposarcoma (DDL). Only one case involved a myxoid liposarcoma. Myxoid liposarcoma is a subtype of liposarcoma and the terminology for liposarcoma with myxoid stroma, which we describe in this report, is different from that for myxoid liposarcoma [6]. There are two patterns of dedifferentiation: high-grade and low-grade dedifferentiation. High-grade dedifferentiation is recognizable as high-grade pleomorphic spindle cell sarcoma with abundant mitoses [7]. Low-grade dedifferentiation presents as a region absent of lipogenic differentiation, having cellularity in excess of that of sclerosing WDL, appearing similar to that of low-grade fibrosarcoma [8]. DDL occasionally shows prominent myxoid stroma, resulting in confusion with other myxoid sarcomas [9]. When DDL with low-grade dedifferentiation shows prominent myxoid stroma, it can lead to diagnostic difficulties, particularly if co-existing WDL is overlooked. Herein, we present a case of paratesticular liposarcoma originating from the spermatic cord. It showed low-grade dedifferentiation accompanied by prominent myxoid stroma.
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Case report A 64-year-old man presented with swelling of the rightside scrotum. He had first noticed it 1 month prior. Physical examination revealed no abnormality in any other part of the body. All laboratory tests were within the normal range. On ultrasonography, a mass was detected inside the right-side scrotum. Subsequently, magnetic resonance imaging was performed. On T1-weighted images, the mass had low signal intensity (Fig. 1a); on T2-weighted images, the mass had high signal intensity (Fig. 1b). After contrast enhancement, the mass became well enhanced (Fig. 1c, d). Due to a suspicion of malignancy, computed tomography was conducted and it revealed no metastatic lesion. A radical orchiectomy and high cord ligation were performed. The surgically resected specimen revealed a mass with a myxoid appearance, which measured 36 9 31 9 28 mm. Along the spermatic cord, slightly discolored fatty tissue with some tiny off-white areas were observed, which measured 55 mm in its maximal dimension (Fig. 2). Macroscopically, the surgical margin of the spermatic cord seemed to be negative. Histopathologically, the myxoid mass corresponded to DDL. The spermatic cord was surrounded by lipoma-like WDL (Fig. 3a). The border between the WDL and DDL was well delineated (Fig. 3b). In the WDL, minor collagenous areas were interspersed among major adipocytic areas. Atypical spindled cells with hyperchromatic and
Fig. 1 Magnetic resonance imaging. a On T1-weighted images, the mass showing low signal intensity (arrow). Asterisk: testis. b On T2weighted image, the mass showing high signal intensity (arrow). Asterisk: testis. (c, d) (c) Axial; (d) sagittal. Contrast enhancement showing a well-enhanced mass (arrows). Asterisks: testis
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enlarged nuclei were scattered in the collagenous areas (Fig. 3c). Lipoblasts were only occasionally observed in the WDL. In the DDL, spindle to oval tumor cells were proliferating within a background of prominent myxoid stroma. Their nuclei were hyperchromatic but not pleomorphic and they were relatively uniform (Fig. 3d); all tumor cells in the DDL exhibited these characteristics. No lipoblast was found in the DDL. The dedifferentiation observed in this tumor was thus diagnosed as low-grade dedifferentiation. At the surgical margin of the spermatic cord, there were atypical spindled cells intermingled with adipocytic areas (Fig. 3e). Immunohistochemically, spindled cells and some adipocytes in the WDL co-expressed cyclin dependent kinase 4 (CDK4; DCS-31, 1:200; Biosource International, Camarillo, CA) (Fig. 4a) and mouse double minute 2 (MDM2; IF2, 1:100; Zymed Laboratories, South San Francisco, CA) (Fig. 4b). Spindle to oval tumor cells in the DDL also co-expressed CDK4 (Fig. 4c) and MDM2 (Fig. 4d). At the surgical margin of the spermatic cord, atypical spindled cells and some adipocytes were immunopositive for CDK4 (Fig. 4e). In the WDL, tumor cells with adipocytic differentiation were immunopositive for S-100 protein (polyclonal, 1:100; Dako, Glostrup, Denmark), whereas spindled tumor cells in the WDL and whole tumor cells in the DDL were immunonegative for S-100 protein. All tumor cells were immunonegative for CD34 (QBEnd 10, 1:100; Dako). The Ki-67 (MIB-1, 1:100; Dako) labeling indexes for the WDL and DDL were 3.2 and 21.8 %, respectively. The diagnosis of DDL, grade 2, was made according to the FNCLCC (French Fe´de´ration Nationale des Centres de
Fig. 2 Macroscopic findings. A mass with myxoid appearance, which measures 36 9 31 9 28 mm, is observed (arrow). Along the spermatic cord, slightly discolored fatty tissue with some small offwhite areas is visible (maximal dimension, 55 mm). Arrowhead: testis
Med Mol Morphol
Fig. 4 Immunohistochemical findings. a Tumor cells in the WDL expressing CDK4 (9400). b Tumor cells in the WDL expressing MDM2 (9400). c Tumor cells in the DDL expressing CDK4 (9400). d Tumor cells in the DDL expressing MDM2 (9400). e At the surgical margin of the spermatic cord, atypical spindled cells are immunopositive for CDK4 (9200). CDK4 cyclin dependent kinase 4, MDM2 mouse double minute 2
Fig. 3 Microscopic findings using hematoxylin and eosin staining. a Histopathologically, the myxoid mass corresponds to DDL. The spermatic cord is surrounded by WDL (912.5). b The border between the WDL and DDL was well delineated (9200). c Higher magnification of the boxed area in the WDL from (a) Collagenous areas are interspersed among adipocytic areas. Atypical spindled cells with hyperchromatic and enlarged nuclei are scattered in the collagenous areas (9400). d Higher magnification of the boxed area in the DDL from (a) corresponding to one of the most cellular areas in this DDL. Spindle to oval tumor cells are proliferating within a background of prominent myxoid stroma. Their nuclei are hyperchromatic but not pleomorphic; they are relatively uniform (9400). e At the surgical margin of the spermatic cord, there are atypical spindled cells (left side) (9200). WDL well-differentiated liposarcoma, DDL dedifferentiated liposarcoma
Lutte Contre le Cancer) system [10, 11]. Considering the histopathological analysis and immunohistochemistry, the surgical margin (cut end of spermatic cord) was positive due to the presence of WDL. The postoperative course was uneventful and localized radiation therapy was planned for the patient. At the time of writing this report, 2 months have passed since the operation was performed, and there have not been any signs of recurrence.
Discussion Paratesticular sarcoma is rare, but liposarcoma is its most common type, followed by leiomyosarcoma, rhabdomyosarcoma, undifferentiated pleomorphic sarcoma, and
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fibrosarcoma [1–4, 12, 13]. DDL with prominent myxoid stroma has been well documented [9], but its origin in the paratesticular region has not been well described in the English literature. Unique in this case is the composition of the DDL with relatively monotonous tumor cells showing non-high-grade and uniform nuclei in addition to prominent myxoid stroma; previously reported DDLs with prominent myxoid stroma were composed of somewhat pleomorphic cells reminiscent of myxofibrosarcoma [9]. Paratesticular liposarcoma tends to be somewhat difficult to differentiate from lipomas of the spermatic cord, which account for most fatty masses in the spermatic cord [14]. However, liposarcomas are usually larger than lipomas. In addition, paratesticular liposarcoma sometimes presents as DDL [5]. The differential diagnoses for lowgrade dedifferentiation, as seen in this case of liposarcoma, are benign and low-grade mesenchymal tumors. The general differential diagnosis of adult spindle cell tumors in the paratesticular region includes low-grade myxofibrosarcoma, low-grade leiomyosarcoma, fibrous mesothelioma, and various benign fibrous tumors including fibromatosis [5]. According to Montgomery et al., paratesticular liposarcoma most commonly develops from the spermatic cord, followed by the testicular tunica, and only rarely arises from the epididymis [5]. In their study of 30 cases of paratesticular liposarcoma, 10 cases were DDLs. Among them, five cases showed high-grade dedifferentiation and the remaining five cases exhibited low-grade dedifferentiation. In DDL, cases with dedifferentiated areas harboring prominent myxoid stroma can be encountered [9]. In such cases, tumor cells in the dedifferentiated area show more or less pleomorphic nuclei and are somewhat similar to myxofibrosarcoma. This pleomorphism is an important clue for differentiating DDL from myxoid liposarcoma, the constituent cells of which are relatively homogenous in appearance. Without such pleomorphism, as was observed in our case, the possibility of mixed-type liposarcoma, such as co-existing WDL and myxoid liposarcoma, cannot easily be ruled out; mixed-type liposarcoma is a combined tumor composed of different histological subtypes of liposarcoma [15]. Approximately 5 % of liposarcomas are categorized as mixed-type liposarcoma [16–18]. In our case, tumor cells in the dedifferentiated area showed a rather monotonous appearance. This observation suggests that the possibility of mixed-type liposarcoma, especially co-existence of myxoid liposarcoma, should be ruled out. Immunohistochemical analysis using CDK4 and MDM2 is of great help when differentiating DDL from myxoid liposarcoma. Both WDL and DDL have supernumerary ring and/or giant chromosomes, composed of amplicons of the 12q13-15 region, which lead to amplification of several genes including CDK4 and MDM2 [19–22]. The resultant
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overexpression of CDK4 and MDM2 proteins can be immunohistochemically demonstrated in both WDL and DDL. On the other hand, their expression is usually not detected in myxoid liposarcoma [23]. In our case, the prominently myxoid dedifferentiated area with relatively monotonous tumor cells revealed expression of both CDK4 and MDM2; the WDL also showed their expression. It is thus valid to interpret the myxoid area in our case as a low-grade dedifferentiation component of DDL rather than to recognize it as myxoid liposarcoma. The surgical margin is prone to be positive in cases of paratesticular liposarcoma. This propensity is mainly due to anatomical limitations during resection [24]. In our case, the surgical margin is microscopically positive with the aid of immunohistochemical analysis using CDK4, even though it seemed negative macroscopically. Regarding detection of tumor cells of WDL, CDK4 is more sensitive and specific than MDM2 [23] and CDK4 would be helpful when encountering equivocal atypical cells on morphological analysis alone. Postoperative radiation therapy is often conducted in cases with a positive surgical margin, since local recurrence rates are high [24]. Adjuvant chemotherapy remains controversial for liposarcoma [25]. In conclusion, this is a unique case of paratesticular DDL with prominent myxoid stroma, which matched the concept of low-grade dedifferentiation, and included relatively uniform atypical cells without pleomorphism to such an extent that it mimicked myxofibrosarcoma. This myxoid component was confidently differentiated from myxoid liposarcoma with the help of immunohistochemical analysis using CDK4 and MDM2. Conflict of interest
None.
References 1. Lioe TF, Biggart JD (1993) Tumours of the spermatic cord and paratesticular tissue. A clinicopathological study. Br J Urol 71(5):600–606 2. Varzaneh FE, Verghese M, Shmookler BM (2002) Paratesticular leiomyosarcoma in an elderly man. Urology 60(6):1112 3. Sogani PC, Grabstald H, Whitmore WF Jr (1978) Spermatic cord sarcoma in adults. J Urol 120(3):301–305 4. Russo P, Brady MS, Conlon K, Hajdu SI, Fair WR, Herr HW, Brennan MF (1992) Adult urological sarcoma. J Urol 147(4):1032–1036 discussion 1036–1037 5. Montgomery E, Fisher C (2003) Paratesticular liposarcoma: a clinicopathologic study. Am J Surg Pathol 27(1):40–47 6. Antonescu CR, Elahi A, Humphrey M, Lui MY, Healey JH, Brennan MF, Woodruff JM, Jhanwar SC, Ladanyi M (2000) Specificity of TLS-CHOP rearrangement for classic myxoid/ round cell liposarcoma: absence in predominantly myxoid welldifferentiated liposarcomas. J Mol Diagn 2(3):132–138. doi:10. 1016/S1525-1578(10)60628-9 7. Evans HL (1979) Liposarcoma: a study of 55 cases with a reassessment of its classification. Am J Surg Pathol 3(6):507–523
Med Mol Morphol 8. Henricks WH, Chu YC, Goldblum JR, Weiss SW (1997) Dedifferentiated liposarcoma: a clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation. Am J Surg Pathol 21(3):271–281 9. Sioletic S, Dal Cin P, Fletcher CD, Hornick JL (2013) Welldifferentiated and dedifferentiated liposarcomas with prominent myxoid stroma: analysis of 56 cases. Histopathology 62(2):287–293. doi:10.1111/j.1365-2559.2012.04348.x 10. Guillou L, Coindre JM, Bonichon F, Nguyen BB, Terrier P, Collin F, Vilain MO, Mandard AM, Le Doussal V, Leroux A, Jacquemier J, Duplay H, Sastre-Garau X, Costa J (1997) Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol 15(1):350–362 11. Trojani M, Contesso G, Coindre JM, Rouesse J, Bui NB, de Mascarel A, Goussot JF, David M, Bonichon F, Lagarde C (1984) Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system. Int J Cancer 33(1):37–42 12. Khoubehi B, Mishra V, Ali M, Motiwala H, Karim O (2002) Adult paratesticular tumours. BJU Int 90(7):707–715 13. Soosay GN, Parkinson MC, Paradinas J, Fisher C (1996) Paratesticular sarcomas revisited: a review of cases in the British Testicular Tumour Panel and Registry. Br J Urol 77(1):143–146 14. Montgomery E, Buras R (1999) Incidental liposarcomas identified during hernia repair operations. J Surg Oncol 71(1):50–53 15. Mentzel T, Palmedo G, Hantschke M, Woziwodzki J, Beck C (2008) Mixed-type liposarcoma: clinicopathological, immunohistochemical, and molecular analysis of a case arising in deep soft tissues of the lower extremity. Virchows Arch 453(2):197–201. doi:10.1007/s00428-008-0624-7 16. Irie T, Hatori M, Watanabe M, Ehara S, Kokubun S (2003) Radiologically and histologically mixed liposarcoma: a report of two biphasic cases. Jpn J Clin Oncol 33(9):482–485 17. Anand Rajan KD, Subbarao KC, Agarwala S, Gupta SD (2010) Mediastinal liposarcoma of mixed type in childhood: a report of a
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case with unusual histologic features. Indian J Pathol Microbiol 53(3):525–528. doi:10.4103/0377-4929.68297 Mentzel T, Fletcher CD (1997) Dedifferentiated myxoid liposarcoma: a clinicopathological study suggesting a closer relationship between myxoid and well-differentiated liposarcoma. Histopathology 30(5):457–463 Nilbert M, Rydholm A, Mitelman F, Meltzer PS, Mandahl N (1995) Characterization of the 12q13-15 amplicon in soft tissue tumors. Cancer Genet Cytogenet 83(1):32–36 Dei Tos AP, Doglioni C, Piccinin S, Sciot R, Furlanetto A, Boiocchi M, Dal Cin P, Maestro R, Fletcher CD, Tallini G (2000) Coordinated expression and amplification of the MDM2, CDK4, and HMGI-C genes in atypical lipomatous tumours. J Pathol 190(5):531–536. doi:10.1002/(SICI)1096-9896(200004)190: 5\531:AID-PATH579[3.0.CO;2-W Pedeutour F, Forus A, Coindre JM, Berner JM, Nicolo G, Michiels JF, Terrier P, Ranchere-Vince D, Collin F, Myklebost O, Turc-Carel C (1999) Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes Cancer 24(1):30–41 Pilotti S, Della Torre G, Lavarino C, Sozzi G, Minoletti F, Vergani B, Azzarelli A, Rilke F, Pierotti MA (1998) Molecular abnormalities in liposarcoma: role of MDM2 and CDK4-containing amplicons at 12q13-22. J Pathol 185(2):188–190. doi:10.1002/ (SICI)1096-9896(199806)185:2\188:AID-PATH53[3.0.CO;2-2 Thway K, Flora R, Shah C, Olmos D, Fisher C (2012) Diagnostic utility of p16, CDK4, and MDM2 as an immunohistochemical panel in distinguishing well-differentiated and dedifferentiated liposarcomas from other adipocytic tumors. Am J Surg Pathol 36(3):462–469. doi:10.1097/PAS.0b013e3182417330 Catton C, Jewett M, O’Sullivan B, Kandel R (1999) Paratesticular sarcoma: failure patterns after definitive local therapy. J Urol 161(6):1844–1847 Sarcoma Meta-analysis Collaboration (SMAC) (2000) Adjuvant chemotherapy for localised resectable soft tissue sarcoma in adults. Cochrane Database Syst Rev (4):CD001419. doi:10.1002/ 14651858.CD001419
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CASE REPORT
Paratesticular dedifferentiated liposarcoma with prominent myxoid stroma: report of a case and review of the literature Shogo Tajima1 • Kenji Koda2
Received: 31 March 2015 / Accepted: 8 May 2015 Ó The Japanese Society for Clinical Molecular Morphology 2015
Abstract Paratesticular sarcoma is rare, but liposarcoma is its most common type. Paratesticular liposarcoma sometimes presents as dedifferentiated liposarcoma. Both high-grade and low-grade dedifferentiation have been reported. Herein, we presented a unique case of a 64-year-old man with low-grade dedifferentiated liposarcoma with prominent myxoid stroma. Well-differentiated liposarcoma components extended along the spermatic cord. The constituent cells of the dedifferentiated component were peculiar in that, they were relatively uniform cells with atypia and did not have pleomorphism to such an extent that it mimicked myxofibrosarcoma. This myxoid component was confidently differentiated from myxoid liposarcoma with the help of immunohistochemical analysis using CDK4 and MDM2. These two markers were also expressed in the well-differentiated component. It could therefore be confirmed that this sarcoma is dedifferentiated liposarcoma but is not mixed-type liposarcoma comprising well-differentiated liposarcoma and myxoid liposarcoma.
& Shogo Tajima [email protected] 1
Department of Pathology, Shizuoka Saiseikai General Hospital, 1-1-1 Oshika, Suruga-ku, Shizuoka 422-8021, Japan
2
Department of Pathology, Fujieda Municipal General Hospital, Shizuoka, Japan
Keywords Spermatic cord Paratesticular liposarcoma Dedifferentiated liposarcoma Myxoid stroma CDK4 MDM2
Introduction Paratesticular tumors account for 2–3 % of all scrotal tumors. They originate from the spermatic cord, testicular tunica, or epididymis [1–4]. Paratesticular liposarcomas had been reported as single case studies or as components of larger series, until Montgomery et al. reported 30 paratesticular LPSs [5]. Among them, 19 cases were of well-differentiated liposarcoma (WDL), and 10 cases were of dedifferentiated liposarcoma (DDL). Only one case involved a myxoid liposarcoma. Myxoid liposarcoma is a subtype of liposarcoma and the terminology for liposarcoma with myxoid stroma, which we describe in this report, is different from that for myxoid liposarcoma [6]. There are two patterns of dedifferentiation: high-grade and low-grade dedifferentiation. High-grade dedifferentiation is recognizable as high-grade pleomorphic spindle cell sarcoma with abundant mitoses [7]. Low-grade dedifferentiation presents as a region absent of lipogenic differentiation, having cellularity in excess of that of sclerosing WDL, appearing similar to that of low-grade fibrosarcoma [8]. DDL occasionally shows prominent myxoid stroma, resulting in confusion with other myxoid sarcomas [9]. When DDL with low-grade dedifferentiation shows prominent myxoid stroma, it can lead to diagnostic difficulties, particularly if co-existing WDL is overlooked. Herein, we present a case of paratesticular liposarcoma originating from the spermatic cord. It showed low-grade dedifferentiation accompanied by prominent myxoid stroma.
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Case report A 64-year-old man presented with swelling of the rightside scrotum. He had first noticed it 1 month prior. Physical examination revealed no abnormality in any other part of the body. All laboratory tests were within the normal range. On ultrasonography, a mass was detected inside the right-side scrotum. Subsequently, magnetic resonance imaging was performed. On T1-weighted images, the mass had low signal intensity (Fig. 1a); on T2-weighted images, the mass had high signal intensity (Fig. 1b). After contrast enhancement, the mass became well enhanced (Fig. 1c, d). Due to a suspicion of malignancy, computed tomography was conducted and it revealed no metastatic lesion. A radical orchiectomy and high cord ligation were performed. The surgically resected specimen revealed a mass with a myxoid appearance, which measured 36 9 31 9 28 mm. Along the spermatic cord, slightly discolored fatty tissue with some tiny off-white areas were observed, which measured 55 mm in its maximal dimension (Fig. 2). Macroscopically, the surgical margin of the spermatic cord seemed to be negative. Histopathologically, the myxoid mass corresponded to DDL. The spermatic cord was surrounded by lipoma-like WDL (Fig. 3a). The border between the WDL and DDL was well delineated (Fig. 3b). In the WDL, minor collagenous areas were interspersed among major adipocytic areas. Atypical spindled cells with hyperchromatic and
Fig. 1 Magnetic resonance imaging. a On T1-weighted images, the mass showing low signal intensity (arrow). Asterisk: testis. b On T2weighted image, the mass showing high signal intensity (arrow). Asterisk: testis. (c, d) (c) Axial; (d) sagittal. Contrast enhancement showing a well-enhanced mass (arrows). Asterisks: testis
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enlarged nuclei were scattered in the collagenous areas (Fig. 3c). Lipoblasts were only occasionally observed in the WDL. In the DDL, spindle to oval tumor cells were proliferating within a background of prominent myxoid stroma. Their nuclei were hyperchromatic but not pleomorphic and they were relatively uniform (Fig. 3d); all tumor cells in the DDL exhibited these characteristics. No lipoblast was found in the DDL. The dedifferentiation observed in this tumor was thus diagnosed as low-grade dedifferentiation. At the surgical margin of the spermatic cord, there were atypical spindled cells intermingled with adipocytic areas (Fig. 3e). Immunohistochemically, spindled cells and some adipocytes in the WDL co-expressed cyclin dependent kinase 4 (CDK4; DCS-31, 1:200; Biosource International, Camarillo, CA) (Fig. 4a) and mouse double minute 2 (MDM2; IF2, 1:100; Zymed Laboratories, South San Francisco, CA) (Fig. 4b). Spindle to oval tumor cells in the DDL also co-expressed CDK4 (Fig. 4c) and MDM2 (Fig. 4d). At the surgical margin of the spermatic cord, atypical spindled cells and some adipocytes were immunopositive for CDK4 (Fig. 4e). In the WDL, tumor cells with adipocytic differentiation were immunopositive for S-100 protein (polyclonal, 1:100; Dako, Glostrup, Denmark), whereas spindled tumor cells in the WDL and whole tumor cells in the DDL were immunonegative for S-100 protein. All tumor cells were immunonegative for CD34 (QBEnd 10, 1:100; Dako). The Ki-67 (MIB-1, 1:100; Dako) labeling indexes for the WDL and DDL were 3.2 and 21.8 %, respectively. The diagnosis of DDL, grade 2, was made according to the FNCLCC (French Fe´de´ration Nationale des Centres de
Fig. 2 Macroscopic findings. A mass with myxoid appearance, which measures 36 9 31 9 28 mm, is observed (arrow). Along the spermatic cord, slightly discolored fatty tissue with some small offwhite areas is visible (maximal dimension, 55 mm). Arrowhead: testis
Med Mol Morphol
Fig. 4 Immunohistochemical findings. a Tumor cells in the WDL expressing CDK4 (9400). b Tumor cells in the WDL expressing MDM2 (9400). c Tumor cells in the DDL expressing CDK4 (9400). d Tumor cells in the DDL expressing MDM2 (9400). e At the surgical margin of the spermatic cord, atypical spindled cells are immunopositive for CDK4 (9200). CDK4 cyclin dependent kinase 4, MDM2 mouse double minute 2
Fig. 3 Microscopic findings using hematoxylin and eosin staining. a Histopathologically, the myxoid mass corresponds to DDL. The spermatic cord is surrounded by WDL (912.5). b The border between the WDL and DDL was well delineated (9200). c Higher magnification of the boxed area in the WDL from (a) Collagenous areas are interspersed among adipocytic areas. Atypical spindled cells with hyperchromatic and enlarged nuclei are scattered in the collagenous areas (9400). d Higher magnification of the boxed area in the DDL from (a) corresponding to one of the most cellular areas in this DDL. Spindle to oval tumor cells are proliferating within a background of prominent myxoid stroma. Their nuclei are hyperchromatic but not pleomorphic; they are relatively uniform (9400). e At the surgical margin of the spermatic cord, there are atypical spindled cells (left side) (9200). WDL well-differentiated liposarcoma, DDL dedifferentiated liposarcoma
Lutte Contre le Cancer) system [10, 11]. Considering the histopathological analysis and immunohistochemistry, the surgical margin (cut end of spermatic cord) was positive due to the presence of WDL. The postoperative course was uneventful and localized radiation therapy was planned for the patient. At the time of writing this report, 2 months have passed since the operation was performed, and there have not been any signs of recurrence.
Discussion Paratesticular sarcoma is rare, but liposarcoma is its most common type, followed by leiomyosarcoma, rhabdomyosarcoma, undifferentiated pleomorphic sarcoma, and
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fibrosarcoma [1–4, 12, 13]. DDL with prominent myxoid stroma has been well documented [9], but its origin in the paratesticular region has not been well described in the English literature. Unique in this case is the composition of the DDL with relatively monotonous tumor cells showing non-high-grade and uniform nuclei in addition to prominent myxoid stroma; previously reported DDLs with prominent myxoid stroma were composed of somewhat pleomorphic cells reminiscent of myxofibrosarcoma [9]. Paratesticular liposarcoma tends to be somewhat difficult to differentiate from lipomas of the spermatic cord, which account for most fatty masses in the spermatic cord [14]. However, liposarcomas are usually larger than lipomas. In addition, paratesticular liposarcoma sometimes presents as DDL [5]. The differential diagnoses for lowgrade dedifferentiation, as seen in this case of liposarcoma, are benign and low-grade mesenchymal tumors. The general differential diagnosis of adult spindle cell tumors in the paratesticular region includes low-grade myxofibrosarcoma, low-grade leiomyosarcoma, fibrous mesothelioma, and various benign fibrous tumors including fibromatosis [5]. According to Montgomery et al., paratesticular liposarcoma most commonly develops from the spermatic cord, followed by the testicular tunica, and only rarely arises from the epididymis [5]. In their study of 30 cases of paratesticular liposarcoma, 10 cases were DDLs. Among them, five cases showed high-grade dedifferentiation and the remaining five cases exhibited low-grade dedifferentiation. In DDL, cases with dedifferentiated areas harboring prominent myxoid stroma can be encountered [9]. In such cases, tumor cells in the dedifferentiated area show more or less pleomorphic nuclei and are somewhat similar to myxofibrosarcoma. This pleomorphism is an important clue for differentiating DDL from myxoid liposarcoma, the constituent cells of which are relatively homogenous in appearance. Without such pleomorphism, as was observed in our case, the possibility of mixed-type liposarcoma, such as co-existing WDL and myxoid liposarcoma, cannot easily be ruled out; mixed-type liposarcoma is a combined tumor composed of different histological subtypes of liposarcoma [15]. Approximately 5 % of liposarcomas are categorized as mixed-type liposarcoma [16–18]. In our case, tumor cells in the dedifferentiated area showed a rather monotonous appearance. This observation suggests that the possibility of mixed-type liposarcoma, especially co-existence of myxoid liposarcoma, should be ruled out. Immunohistochemical analysis using CDK4 and MDM2 is of great help when differentiating DDL from myxoid liposarcoma. Both WDL and DDL have supernumerary ring and/or giant chromosomes, composed of amplicons of the 12q13-15 region, which lead to amplification of several genes including CDK4 and MDM2 [19–22]. The resultant
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overexpression of CDK4 and MDM2 proteins can be immunohistochemically demonstrated in both WDL and DDL. On the other hand, their expression is usually not detected in myxoid liposarcoma [23]. In our case, the prominently myxoid dedifferentiated area with relatively monotonous tumor cells revealed expression of both CDK4 and MDM2; the WDL also showed their expression. It is thus valid to interpret the myxoid area in our case as a low-grade dedifferentiation component of DDL rather than to recognize it as myxoid liposarcoma. The surgical margin is prone to be positive in cases of paratesticular liposarcoma. This propensity is mainly due to anatomical limitations during resection [24]. In our case, the surgical margin is microscopically positive with the aid of immunohistochemical analysis using CDK4, even though it seemed negative macroscopically. Regarding detection of tumor cells of WDL, CDK4 is more sensitive and specific than MDM2 [23] and CDK4 would be helpful when encountering equivocal atypical cells on morphological analysis alone. Postoperative radiation therapy is often conducted in cases with a positive surgical margin, since local recurrence rates are high [24]. Adjuvant chemotherapy remains controversial for liposarcoma [25]. In conclusion, this is a unique case of paratesticular DDL with prominent myxoid stroma, which matched the concept of low-grade dedifferentiation, and included relatively uniform atypical cells without pleomorphism to such an extent that it mimicked myxofibrosarcoma. This myxoid component was confidently differentiated from myxoid liposarcoma with the help of immunohistochemical analysis using CDK4 and MDM2. Conflict of interest
None.
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