Med Mol Morphol DOI 10.1007/s00795-015-0103-6
CASE REPORT
Pleomorphic leiomyosarcoma with a dedifferentiation-like appearance in the kidney: case report and literature review Shogo Tajima1 • Michihiko Waki1 • Masashi Fukuyama1
Received: 13 March 2015 / Accepted: 16 April 2015 Ó The Japanese Society for Clinical Molecular Morphology 2015
Abstract Although primary leiomyosarcoma of the kidney is extremely rare, it is the most common sarcoma of the kidney. Leiomyosarcoma with a large pleomorphic component is designated as pleomorphic leiomyosarcoma. The pleomorphic component is usually similar to undifferentiated high-grade pleomorphic sarcoma, although it variably expresses smooth muscle markers on immunohistochemistry. In the few reported cases of pleomorphic leiomyosarcoma of the kidney, cases with the pleomorphic component showing distinct nodularity similar to dedifferentiated leiomyosarcoma have not been described, to the best of our knowledge. Herein, we present a case of a 49-year-old woman with pleomorphic leiomyosarcoma in the kidney showing distinct nodularity of smooth muscle marker-expressing pleomorphic cells within a background of classic leiomyosarcoma. Along with the classification as a pleomorphic leiomyosarcoma, suggesting aggressive clinical behavior, the renal origin itself might also be a predictor of poor prognosis, as shown in a previous study. This case also involved concomitant distant metastases, already present during the initial detection of the renal tumor.
& Shogo Tajima [email protected] 1
Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
Keywords Kidney Pleomorphic leiomyosarcoma Dedifferentiation Metastasis Prognosis
Introduction Primary leiomyosarcoma is the most common sarcoma of the kidney but accounts for only 0.1 % of all invasive renal tumors [1, 2]. In classic leiomyosarcoma, small foci of pleomorphic cells are sometimes observed [3]. Leiomyosarcoma with a large pleomorphic component is designated as pleomorphic leiomyosarcoma [4]. The pleomorphic component is usually similar to undifferentiated high-grade pleomorphic sarcoma, although this variably expresses smooth muscle markers on immunohistochemistry (IHC) [3, 4]. On the other hand, dedifferentiated leiomyosarcoma, which is morphologically characterized by an abrupt transition from classic leiomyosarcoma to high-grade sarcoma, does not express any smooth muscle markers in the high-grade component [5]. To the best of our knowledge, dedifferentiated leiomyosarcoma has not been documented in the kidney. Overall, there have been few reported cases of pleomorphic leiomyosarcoma of the kidney [3]. Among pleomorphic leiomyosarcomas of the kidney, cases showing distinct nodularity of pleomorphic cells have not been described. Herein, we present a case of a 49-year-old woman with pleomorphic leiomyosarcoma in the kidney showing distinct nodularity of pleomorphic cells along with classic leiomyosarcoma outside the nodule. Although the expression of smooth muscle markers was low in the pleomorphic cells, markers expressed in classic leiomyosarcoma were also expressed in pleomorphic cells.
123
Med Mol Morphol
Clinical summary
Pathological findings
A 49-year-old woman was incidentally found to have a tumor and hydronephrosis in the right kidney by contrastenhanced computed tomography (CT), performed to examine numbness in her right leg. The renal tumor was located at the upper pole of the right kidney and bulged into the surrounding fat tissue. CT also revealed metastases of the renal tumor in the lung, liver, bone, and lymph nodes of the renal hilum. On fat-suppressed T2-weighted magnetic resonance imaging (MRI), the tumor had two components, a major component with low intensity and a minor component situated at the outer part of the tumor exhibiting moderate intensity with a low-intensity central area (Fig. 1a). On fat-suppressed contrast-enhanced images, the major component was mildly enhanced, but the minor component had a non-enhanced area at the center with a surrounding area showing similar enhancement to the major component (Fig. 1b). The major component displayed high intensity and the minor component (except for the central area with low intensity) displayed very high intensity on diffusion-weighted images (Fig. 1c). The renal tumor was 53 9 42 9 45 mm. The minor component was 28 9 22 9 18 mm. The liver metastases displayed similar signal intensity to the peripheral area of the minor component (Fig. 1a–c, arrows). On suspicion of renal cell carcinoma, a right nephrectomy was performed. The postoperative course was uneventful. At the time of writing, the patient is still alive with pre-existing metastatic tumors 3 months after the operation. No local recurrence has been found.
The surgically resected specimen revealed an off-white tumor with a hemorrhagic area in the outer part of the tumor (Fig. 2a). On the cut surface, the tumor had an area of hemorrhage within the background of the off-white tumor. Around the area of hemorrhage, necrotic tumor tissue was observed (Fig. 2b). It was difficult to distinguish viable tumor tissue surrounding the necrotic tissue from the rest of the tumor tissue, in contrast to the clear distinction observed in MRI. Histopathologically, the tumor comprised two components. The boundary between these two components was well delineated. Necrosis was present in the center of one component (Fig. 3a). One component was composed of spindle cells with eosinophilic cytoplasm forming interlacing fascicles, accounting for 80 % of the whole tumor. These had moderately enlarged blunt-ended nuclei with hyperchromasia and indistinct nucleoli (Fig. 3b). The mitotic rate was up to 6 per 10 high-power fields (HPFs) (Fig. 3c). The other component consisted of pleomorphic tumor cells with frequently observed highly enlarged and bizarre nuclei presenting hyperchromasia and indistinct nucleoli, occupying 20 % of the whole tumor. Inflammatory cell infiltration, especially by lymphocytes, was prominent (Fig. 3d). The mitotic rate was up to 16 per 10 HPFs (Fig. 3e). The results of IHC are summarized in Table 1. Both the spindle and pleomorphic components were moderately positive for alpha smooth muscle actin (aSMA) (Fig. 4a, b). Both components were strongly positive for muscle
Fig. 1 Magnetic resonance imaging. a On fat-suppressed T2-weighted images, the tumor had two components. The major component showed low intensity and the minor component situated at the periphery of the tumor exhibited moderate intensity with a lowintensity central area. A liver metastasis was observed (arrow). b On fat-suppressed contrast-enhanced images, the major component was mildly enhanced. However, the minor component had a non-enhanced
area at its center, with the surrounding area showing enhancement similar to the major component. A liver metastasis was detected (arrow). c On diffusion-weighted images, the major component displayed high intensity and the minor component displayed very high intensity, except for a low-intensity central area. A liver metastasis was detected (arrow)
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Med Mol Morphol
Fig. 2 Gross findings of the surgically resected specimen. a A offwhite tumor was observed, with a hemorrhagic area (arrows) in the outer part of the tumor. b On the cut surface, the tumor had a hemorrhage area within a background of the off-white tumor. Around the area of hemorrhage, necrotic tumor tissue was observed (arrows)
specific actin (MSA), although some cells in the pleomorphic component did not show MSA immunostaining (Fig. 4c, d). Both components were negative for desmin (Fig. 4e, f). Both components were strongly immunopositive for caldesmon, although some cells in the pleomorphic component showed weak to moderate immunopositivity (Fig. 4g, h). Both components were negative for pan-cytokeratin, melanosome, and c-kit. The Ki-67 labeling indexes were 18.2 % (182 per 1000 counted cells) and 42.8 % (428 per 1000 counted cells) in the spindle cell component and the pleomorphic component, respectively. This tumor was classified as a pleomorphic leiomyosarcoma with a dedifferentiation-like appearance, placing emphasis on the distinct nodularity of the pleomorphic tumor cells. The surgical margin was free of tumor cells.
Discussion Primary leiomyosarcoma of the kidney should be diagnosed with caution, since the majority of malignant tumors with spindle cell morphology are sarcomatoid carcinomas [6]. Sarcomatoid carcinoma is often immunopositive for keratins, whereas leiomyosarcoma is only very rarely
immunopositive for keratin [7]. When nuclear atypia in the spindle cells of renal leiomyosarcoma is not very prominent, angiomyolipoma with a monophasic smooth muscle cell-like component is included in the differential diagnosis, both of which express smooth muscle markers [8]. Angiomyolipoma is differentiated from leiomyosarcoma by the expression of melanocytic markers. In our case, lack of expression of cytokeratin and melanocytic markers, along with expression of the variable smooth muscle marker, confirmed that the tumor should be included in the category of leiomyosarcoma. Expression patterns of smooth muscle myosin heavy chain (MHC) isoforms, such as SM1, SM2, and SMemb (embryonic form of MHC), might be different between the spindle cell component and pleomorphic component. The spindle cell components is expected to express SM1 and SM2, and it might express SMemb focally and weakly, as shown in a previous study [9]. The pleomorphic component with higher proliferative activity than the spindle cell component might express SMemb more strongly than the spindle cell component because smooth muscle cells generally express SMemb when transforming into proliferative forms [10]. In the present study, we could not demonstrate this putative theory owing to the limitations of the study. As for pleomorphic leiomyosarcoma, areas of classic leiomyosarcoma are sometimes minute and may be unnoticed [3]. Approximately, one-third of histologically undifferentiated pleomorphic sarcomas exhibit myogenic differentiation. Most of these were shown to be pleomorphic leiomyosarcomas upon reassessment of morphology and examination by ancillary methods such as IHC and/or electron microscopy [11]. With respect to the diagnosis of pleomorphic leiomyosarcoma, a cutoff ratio of the pleomorphic component to entire tumor is at least 2:3, according to one study showing the aggressive behavior of pleomorphic leiomyosarcoma defined by this standard [4]. However, aggressive behavior has also been reported in four cases of leiomyosarcoma with a pleomorphic component comprising less than two-thirds of the entire tumor (between 40 and 60 %) [3]. A correlation between the extent of the pleomorphic component and prognosis might be unclear for pleomorphic leiomyosarcomas [5, 12]. In the present case, although the pleomorphic component comprised only 20 % of the entire tumor, a distinct nodular area with pleomorphic cells and aggressive behavior revealed by coexisting distant metastases were sufficient indicators of a diagnosis of pleomorphic leiomyosarcoma. According to one study of pleomorphic leiomyosarcoma, metastases were found in 48 % (11 of 23) of patients and 65 % (15 of 23) of patients died of the tumor [4]. In another study of pleomorphic and dedifferentiated
123
Med Mol Morphol
Fig. 3 Microscopic findings. a The tumor comprised of two components that were well delineated (double-headed arrow and dotted arrow). Necrosis was observed at the center of one component (asterisk) (912.5). b Spindle tumor cells with eosinophilic cytoplasm forming interlacing fascicles were observed. They had moderately enlarged blunt-ended nuclei with hyperchromasia and indistinct
nucleoli (9400). c A mitotic figure was observed (arrow) (9600). d Pleomorphic tumor cells were seen with frequently observed, highly enlarged and bizarre nuclei presenting hyperchromasia and indistinct nucleoli. Inflammatory cell infiltration, especially by lymphocytes, was prominent (9400). e Two mitotic figures were observed (arrows) (9600)
Table 1 Antibodies used in the present study and expression of the corresponding markers in the components of leiomyosarcoma via immunohistochemistry
leiomyosarcoma, 89 % (32 of 36) of patients developed metastases and 50 % (18 of 36) of patients died of the tumor [3]. These facts reflect the poor prognosis of pleomorphic leiomyosarcoma. For leiomyosarcoma originating in the kidney, distant metastases were found in 90 % (18 of 20) of patients and 75 % (15 of 20) of patients died of the tumor [13]. No correlation between the examined histologic features and tumor progression has been found in renal leiomyosarcoma. This is due to the poor prognosis of most cases, irrespective of morphologic features [13]. Therefore, it is necessary to carefully treat our patient, since the renal origin itself might predict a poor clinical course of leiomyosarcoma in addition to the morphological designation of pleomorphic leiomyosarcoma. In conclusion, we report a rare case of pleomorphic leiomyosarcoma with a distinct nodular formation of smooth muscle marker-expressing pleomorphic cells within a background of classic leiomyosarcoma. To the best of our knowledge, this morphology has not yet been
Antibodies
Clone
Source
Components of leiomyosarcoma Classic
Pleomorphic
aSMA
1A4
Dako
??
??
MSA
HHF35
Dako
???
??
Desmin
D33
Dako
-
-
Caldesmon
h-CD
Dako
???
??
Pan-cytokeratin
AE1/AE3
Dako
-
-
Melanosome
HMB-45
Dako
-
-
c-kit
Polyclonal
Dako
-
-
Ki-67
MIB-1
Dako
LI: 18.2 %
LI: 42.8 %
Dako Dako, Glostrup, Denmark, aSMA alpha smooth muscle actin, MSA muscle-specific actin, ??? diffuse and strong, ?? intermediate between ??? and ?, ? focal and weak, - negative, LI labeling index
123
Med Mol Morphol
described in the renal context. Along with a classification as pleomorphic leiomyosarcoma, suggesting aggressive clinical behavior, the renal origin itself might be a predictor of poor prognosis. Conflict of interest
None.
References
Fig. 4 Immunohistochemical findings. a The spindle cell component was moderately positive for alpha smooth muscle actin (aSMA) (9400). b The pleomorphic component was moderately positive for aSMA (9400). c The spindle cell component was strongly positive for muscle-specific actin (MSA) (9400). d Some cells in the pleomorphic component were not immunostained for MSA (9400). e The spindle cell component was completely negative for desmin (9400). f The pleomorphic component was completely negative for desmin (9400). g The spindle cell component was strongly immunopositive for caldesmon (9400). h Some cells in the pleomorphic component showed weak to moderate immunopositivity for caldesmon (arrow) (9 400)
1. Kendal WS (2007) The comparative survival of renal leiomyosarcoma. Can J Urol 14(1):3435–3442 2. Moudouni SM, En-Nia I, Rioux-Leclerq N, Guille F, Lobel B (2001) Leiomyosarcoma of the renal pelvis. Scand J Urol Nephrol 35(5):425–427 3. Nicolas MM, Tamboli P, Gomez JA, Czerniak BA (2010) Pleomorphic and dedifferentiated leiomyosarcoma: clinicopathologic and immunohistochemical study of 41 cases. Hum Pathol 41(5):663–671. doi:10.1016/j.humpath.2009.10.005 4. Oda Y, Miyajima K, Kawaguchi K, Tamiya S, Oshiro Y, Hachitanda Y, Oya M, Iwamoto Y, Tsuneyoshi M (2001) Pleomorphic leiomyosarcoma: clinicopathologic and immunohistochemical study with special emphasis on its distinction from ordinary leiomyosarcoma and malignant fibrous histiocytoma. Am J Surg Pathol 25(8):1030–1038 5. Chen E, O’Connell F, Fletcher CD (2011) Dedifferentiated leiomyosarcoma: clinicopathological analysis of 18 cases. Histopathology 59(6):1135–1143. doi:10.1111/j.1365-2559.2011. 04070.x 6. de Peralta-Venturina M, Moch H, Amin M, Tamboli P, Hailemariam S, Mihatsch M, Javidan J, Stricker H, Ro JY, Amin MB (2001) Sarcomatoid differentiation in renal cell carcinoma: a study of 101 cases. Am J Surg Pathol 25(3):275–284 7. Brown DC, Theaker JM, Banks PM, Gatter KC, Mason DY (1987) Cytokeratin expression in smooth muscle and smooth muscle tumours. Histopathology 11(5):477–486 8. Yang L, Feng XL, Shen S, Shan L, Zhang HF, Liu XY, Lv N (2012) Clinicopathological analysis of 156 patients with angiomyolipoma originating from different organs. Oncol Lett 3(3):586–590. doi:10.3892/ol.2012.554 9. Sakurai S, Fukasawa T, Chong JM, Tanaka A, Fukayama M (1999) Embryonic form of smooth muscle myosin heavy chain (SMemb/MHC-B) in gastrointestinal stromal tumor and interstitial cells of Cajal. Am J Pathol 154(1):23–28. doi:10.1016/S00029440(10)65246-7 10. Zhang J, Wang L, Fu W, Wang C, Guo D, Jiang J, Wang Y (2013) Smooth muscle cell phenotypic diversity between dissected and unaffected thoracic aortic media. J Cardiovasc Surg (Torino) 54(4):511–521 11. Fletcher CD (1992) Pleomorphic malignant fibrous histiocytoma: fact or fiction? A critical reappraisal based on 159 tumors diagnosed as pleomorphic sarcoma. Am J Surg Pathol 16(3):213–228 12. 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 13. Miller JS, Zhou M, Brimo F, Guo CC, Epstein JI (2010) Primary leiomyosarcoma of the kidney: a clinicopathologic study of 27 cases. Am J Surg Pathol 34(2):238–242. doi:10.1097/PAS. 0b013e3181cad8c9
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CASE REPORT
Pleomorphic leiomyosarcoma with a dedifferentiation-like appearance in the kidney: case report and literature review Shogo Tajima1 • Michihiko Waki1 • Masashi Fukuyama1
Received: 13 March 2015 / Accepted: 16 April 2015 Ó The Japanese Society for Clinical Molecular Morphology 2015
Abstract Although primary leiomyosarcoma of the kidney is extremely rare, it is the most common sarcoma of the kidney. Leiomyosarcoma with a large pleomorphic component is designated as pleomorphic leiomyosarcoma. The pleomorphic component is usually similar to undifferentiated high-grade pleomorphic sarcoma, although it variably expresses smooth muscle markers on immunohistochemistry. In the few reported cases of pleomorphic leiomyosarcoma of the kidney, cases with the pleomorphic component showing distinct nodularity similar to dedifferentiated leiomyosarcoma have not been described, to the best of our knowledge. Herein, we present a case of a 49-year-old woman with pleomorphic leiomyosarcoma in the kidney showing distinct nodularity of smooth muscle marker-expressing pleomorphic cells within a background of classic leiomyosarcoma. Along with the classification as a pleomorphic leiomyosarcoma, suggesting aggressive clinical behavior, the renal origin itself might also be a predictor of poor prognosis, as shown in a previous study. This case also involved concomitant distant metastases, already present during the initial detection of the renal tumor.
& Shogo Tajima [email protected] 1
Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
Keywords Kidney Pleomorphic leiomyosarcoma Dedifferentiation Metastasis Prognosis
Introduction Primary leiomyosarcoma is the most common sarcoma of the kidney but accounts for only 0.1 % of all invasive renal tumors [1, 2]. In classic leiomyosarcoma, small foci of pleomorphic cells are sometimes observed [3]. Leiomyosarcoma with a large pleomorphic component is designated as pleomorphic leiomyosarcoma [4]. The pleomorphic component is usually similar to undifferentiated high-grade pleomorphic sarcoma, although this variably expresses smooth muscle markers on immunohistochemistry (IHC) [3, 4]. On the other hand, dedifferentiated leiomyosarcoma, which is morphologically characterized by an abrupt transition from classic leiomyosarcoma to high-grade sarcoma, does not express any smooth muscle markers in the high-grade component [5]. To the best of our knowledge, dedifferentiated leiomyosarcoma has not been documented in the kidney. Overall, there have been few reported cases of pleomorphic leiomyosarcoma of the kidney [3]. Among pleomorphic leiomyosarcomas of the kidney, cases showing distinct nodularity of pleomorphic cells have not been described. Herein, we present a case of a 49-year-old woman with pleomorphic leiomyosarcoma in the kidney showing distinct nodularity of pleomorphic cells along with classic leiomyosarcoma outside the nodule. Although the expression of smooth muscle markers was low in the pleomorphic cells, markers expressed in classic leiomyosarcoma were also expressed in pleomorphic cells.
123
Med Mol Morphol
Clinical summary
Pathological findings
A 49-year-old woman was incidentally found to have a tumor and hydronephrosis in the right kidney by contrastenhanced computed tomography (CT), performed to examine numbness in her right leg. The renal tumor was located at the upper pole of the right kidney and bulged into the surrounding fat tissue. CT also revealed metastases of the renal tumor in the lung, liver, bone, and lymph nodes of the renal hilum. On fat-suppressed T2-weighted magnetic resonance imaging (MRI), the tumor had two components, a major component with low intensity and a minor component situated at the outer part of the tumor exhibiting moderate intensity with a low-intensity central area (Fig. 1a). On fat-suppressed contrast-enhanced images, the major component was mildly enhanced, but the minor component had a non-enhanced area at the center with a surrounding area showing similar enhancement to the major component (Fig. 1b). The major component displayed high intensity and the minor component (except for the central area with low intensity) displayed very high intensity on diffusion-weighted images (Fig. 1c). The renal tumor was 53 9 42 9 45 mm. The minor component was 28 9 22 9 18 mm. The liver metastases displayed similar signal intensity to the peripheral area of the minor component (Fig. 1a–c, arrows). On suspicion of renal cell carcinoma, a right nephrectomy was performed. The postoperative course was uneventful. At the time of writing, the patient is still alive with pre-existing metastatic tumors 3 months after the operation. No local recurrence has been found.
The surgically resected specimen revealed an off-white tumor with a hemorrhagic area in the outer part of the tumor (Fig. 2a). On the cut surface, the tumor had an area of hemorrhage within the background of the off-white tumor. Around the area of hemorrhage, necrotic tumor tissue was observed (Fig. 2b). It was difficult to distinguish viable tumor tissue surrounding the necrotic tissue from the rest of the tumor tissue, in contrast to the clear distinction observed in MRI. Histopathologically, the tumor comprised two components. The boundary between these two components was well delineated. Necrosis was present in the center of one component (Fig. 3a). One component was composed of spindle cells with eosinophilic cytoplasm forming interlacing fascicles, accounting for 80 % of the whole tumor. These had moderately enlarged blunt-ended nuclei with hyperchromasia and indistinct nucleoli (Fig. 3b). The mitotic rate was up to 6 per 10 high-power fields (HPFs) (Fig. 3c). The other component consisted of pleomorphic tumor cells with frequently observed highly enlarged and bizarre nuclei presenting hyperchromasia and indistinct nucleoli, occupying 20 % of the whole tumor. Inflammatory cell infiltration, especially by lymphocytes, was prominent (Fig. 3d). The mitotic rate was up to 16 per 10 HPFs (Fig. 3e). The results of IHC are summarized in Table 1. Both the spindle and pleomorphic components were moderately positive for alpha smooth muscle actin (aSMA) (Fig. 4a, b). Both components were strongly positive for muscle
Fig. 1 Magnetic resonance imaging. a On fat-suppressed T2-weighted images, the tumor had two components. The major component showed low intensity and the minor component situated at the periphery of the tumor exhibited moderate intensity with a lowintensity central area. A liver metastasis was observed (arrow). b On fat-suppressed contrast-enhanced images, the major component was mildly enhanced. However, the minor component had a non-enhanced
area at its center, with the surrounding area showing enhancement similar to the major component. A liver metastasis was detected (arrow). c On diffusion-weighted images, the major component displayed high intensity and the minor component displayed very high intensity, except for a low-intensity central area. A liver metastasis was detected (arrow)
123
Med Mol Morphol
Fig. 2 Gross findings of the surgically resected specimen. a A offwhite tumor was observed, with a hemorrhagic area (arrows) in the outer part of the tumor. b On the cut surface, the tumor had a hemorrhage area within a background of the off-white tumor. Around the area of hemorrhage, necrotic tumor tissue was observed (arrows)
specific actin (MSA), although some cells in the pleomorphic component did not show MSA immunostaining (Fig. 4c, d). Both components were negative for desmin (Fig. 4e, f). Both components were strongly immunopositive for caldesmon, although some cells in the pleomorphic component showed weak to moderate immunopositivity (Fig. 4g, h). Both components were negative for pan-cytokeratin, melanosome, and c-kit. The Ki-67 labeling indexes were 18.2 % (182 per 1000 counted cells) and 42.8 % (428 per 1000 counted cells) in the spindle cell component and the pleomorphic component, respectively. This tumor was classified as a pleomorphic leiomyosarcoma with a dedifferentiation-like appearance, placing emphasis on the distinct nodularity of the pleomorphic tumor cells. The surgical margin was free of tumor cells.
Discussion Primary leiomyosarcoma of the kidney should be diagnosed with caution, since the majority of malignant tumors with spindle cell morphology are sarcomatoid carcinomas [6]. Sarcomatoid carcinoma is often immunopositive for keratins, whereas leiomyosarcoma is only very rarely
immunopositive for keratin [7]. When nuclear atypia in the spindle cells of renal leiomyosarcoma is not very prominent, angiomyolipoma with a monophasic smooth muscle cell-like component is included in the differential diagnosis, both of which express smooth muscle markers [8]. Angiomyolipoma is differentiated from leiomyosarcoma by the expression of melanocytic markers. In our case, lack of expression of cytokeratin and melanocytic markers, along with expression of the variable smooth muscle marker, confirmed that the tumor should be included in the category of leiomyosarcoma. Expression patterns of smooth muscle myosin heavy chain (MHC) isoforms, such as SM1, SM2, and SMemb (embryonic form of MHC), might be different between the spindle cell component and pleomorphic component. The spindle cell components is expected to express SM1 and SM2, and it might express SMemb focally and weakly, as shown in a previous study [9]. The pleomorphic component with higher proliferative activity than the spindle cell component might express SMemb more strongly than the spindle cell component because smooth muscle cells generally express SMemb when transforming into proliferative forms [10]. In the present study, we could not demonstrate this putative theory owing to the limitations of the study. As for pleomorphic leiomyosarcoma, areas of classic leiomyosarcoma are sometimes minute and may be unnoticed [3]. Approximately, one-third of histologically undifferentiated pleomorphic sarcomas exhibit myogenic differentiation. Most of these were shown to be pleomorphic leiomyosarcomas upon reassessment of morphology and examination by ancillary methods such as IHC and/or electron microscopy [11]. With respect to the diagnosis of pleomorphic leiomyosarcoma, a cutoff ratio of the pleomorphic component to entire tumor is at least 2:3, according to one study showing the aggressive behavior of pleomorphic leiomyosarcoma defined by this standard [4]. However, aggressive behavior has also been reported in four cases of leiomyosarcoma with a pleomorphic component comprising less than two-thirds of the entire tumor (between 40 and 60 %) [3]. A correlation between the extent of the pleomorphic component and prognosis might be unclear for pleomorphic leiomyosarcomas [5, 12]. In the present case, although the pleomorphic component comprised only 20 % of the entire tumor, a distinct nodular area with pleomorphic cells and aggressive behavior revealed by coexisting distant metastases were sufficient indicators of a diagnosis of pleomorphic leiomyosarcoma. According to one study of pleomorphic leiomyosarcoma, metastases were found in 48 % (11 of 23) of patients and 65 % (15 of 23) of patients died of the tumor [4]. In another study of pleomorphic and dedifferentiated
123
Med Mol Morphol
Fig. 3 Microscopic findings. a The tumor comprised of two components that were well delineated (double-headed arrow and dotted arrow). Necrosis was observed at the center of one component (asterisk) (912.5). b Spindle tumor cells with eosinophilic cytoplasm forming interlacing fascicles were observed. They had moderately enlarged blunt-ended nuclei with hyperchromasia and indistinct
nucleoli (9400). c A mitotic figure was observed (arrow) (9600). d Pleomorphic tumor cells were seen with frequently observed, highly enlarged and bizarre nuclei presenting hyperchromasia and indistinct nucleoli. Inflammatory cell infiltration, especially by lymphocytes, was prominent (9400). e Two mitotic figures were observed (arrows) (9600)
Table 1 Antibodies used in the present study and expression of the corresponding markers in the components of leiomyosarcoma via immunohistochemistry
leiomyosarcoma, 89 % (32 of 36) of patients developed metastases and 50 % (18 of 36) of patients died of the tumor [3]. These facts reflect the poor prognosis of pleomorphic leiomyosarcoma. For leiomyosarcoma originating in the kidney, distant metastases were found in 90 % (18 of 20) of patients and 75 % (15 of 20) of patients died of the tumor [13]. No correlation between the examined histologic features and tumor progression has been found in renal leiomyosarcoma. This is due to the poor prognosis of most cases, irrespective of morphologic features [13]. Therefore, it is necessary to carefully treat our patient, since the renal origin itself might predict a poor clinical course of leiomyosarcoma in addition to the morphological designation of pleomorphic leiomyosarcoma. In conclusion, we report a rare case of pleomorphic leiomyosarcoma with a distinct nodular formation of smooth muscle marker-expressing pleomorphic cells within a background of classic leiomyosarcoma. To the best of our knowledge, this morphology has not yet been
Antibodies
Clone
Source
Components of leiomyosarcoma Classic
Pleomorphic
aSMA
1A4
Dako
??
??
MSA
HHF35
Dako
???
??
Desmin
D33
Dako
-
-
Caldesmon
h-CD
Dako
???
??
Pan-cytokeratin
AE1/AE3
Dako
-
-
Melanosome
HMB-45
Dako
-
-
c-kit
Polyclonal
Dako
-
-
Ki-67
MIB-1
Dako
LI: 18.2 %
LI: 42.8 %
Dako Dako, Glostrup, Denmark, aSMA alpha smooth muscle actin, MSA muscle-specific actin, ??? diffuse and strong, ?? intermediate between ??? and ?, ? focal and weak, - negative, LI labeling index
123
Med Mol Morphol
described in the renal context. Along with a classification as pleomorphic leiomyosarcoma, suggesting aggressive clinical behavior, the renal origin itself might be a predictor of poor prognosis. Conflict of interest
None.
References
Fig. 4 Immunohistochemical findings. a The spindle cell component was moderately positive for alpha smooth muscle actin (aSMA) (9400). b The pleomorphic component was moderately positive for aSMA (9400). c The spindle cell component was strongly positive for muscle-specific actin (MSA) (9400). d Some cells in the pleomorphic component were not immunostained for MSA (9400). e The spindle cell component was completely negative for desmin (9400). f The pleomorphic component was completely negative for desmin (9400). g The spindle cell component was strongly immunopositive for caldesmon (9400). h Some cells in the pleomorphic component showed weak to moderate immunopositivity for caldesmon (arrow) (9 400)
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