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Case Report | Open Access

Primary Renal Leiomyosarcoma: Case Report and Review of the Literature

Sunil V Jagtap1, Shubham S. Jagtap2, kaushiki Varshney3, Yogesh Jadhav4, Pranjal Shah3

1Professor, Department of Pathology, Krishna Institute of Medical Sciences Deemed University, Karad, India.

2Assistant Lecturer, Department of Medicine, Krishna Institute of Medical Sciences Deemed University, Karad, India.

3Assistant Lecturer, Department of Pathology, Krishna Institute of Medical Sciences Deemed University, Karad, India.

4Assistant Professor, Department of Surgery, Krishna Institute of Medical Sciences Deemed University, Karad, India.

Correspondence: Sunil Vitthalrao Jagtap (Department of Pathology, Krishna Institute of Medical Sciences, Deemed University, karad 415110, Maharashtra, India; Email: drsvjagtap@gmail.com).

Annals of Urologic Oncology 2023, 6(1): 32-38. https://doi.org/10.32948/auo.2023.01.28

Received: 14 Jan 2023 | Accepted: 29 Jan 2023 | Published online: 09 Feb 2023

Abstract
Renal leiomyosarcoma is an extremely rare malignant tumor. On clinical presentation and radio imaging it is challenging to make an accurate preoperative diagnosis. In our case, a 59-year-old female presented with history of left-sided flank pain, intermittent hematuria and weight loss of 6 months duration. She was known case of hypertension and diabetes mellitus of 20 years and on regular treatment. On the abdomino-pelvis sonography showed an exophytic cortical mass lesion measuring 4.0 x 3.8 cm lesion. Magnetic resonance imaging abdomen and pelvis (plain) shows a well defined non encapsulated exophytic predominantly solid mass lesion measuring 4.3 x 4 x 4.5 cm is noted in the anterior cortex of left kidney at interpolar region. There was no evidence of any regionalor distant metastesis. Patient underwent left radical nephrectomy. On histopathology reported as renal leiomyosarcoma. Immuhistochemistry showed smooth muscle actin diffusely and desmin focally positive. We present this review of rare case of primary renal leiomyosarcoma for its clinical presentation, radiographic findings, and pathologic features.

Key words renal leiomyosarcoma, mesenchymal tumors of kidney, sarcomatoid renal carcinoma, kidney tumors
Introduction
Renal Leiomyosarcoma (LMS) is an exceedingly uncommon tumor, accounting for 0.12% of renal malignancies [1]. It is challenging to make an accurate preoperative diagnosis related to its nonspecific diagnostic features on clinical and radiological findings. It is frequently diagnosed on histological examination. It may present similarly to other renal malignancies. On histologically LMS has to be differentiated from various mesenchymal tumors of kidney expecialy renal sarcomas. Grigon et al. suggested the following criteria should be met to make a diagnosis of primary renal sarcoma. The patient must not have or have had a sarcoma elsewhere to rule out metastasis, on gross morphological examination must be compatible with origin in the kidney rather than involvement due to retroperitoneal sarcoma, and sarcomatoid renal cell carcinoma must be excluded [2]. The generous renal tissue sampling and special techniques like  immunohistochemistry, molecular study, electron microscopy, etc are some time required  before the diagnosis of any primary renal  sarcoma. 
Case report
A 59-year-old female presented with hematuria, left-sided flank pain, gradual enlarging abdominal mass and weight loss of 6 months. Patient was known case of hypertension of last 25 years and diabetes mellitus since last 10 years and was on regular treatment. She was operated for cholecystectomy 25 year back. On per abdomen examination noted a soft, tender, palpable mass at left flank measuring about 6 x 6 cm. The abdomen was slightly distended. Clinically it was suspected of renal mass lesion. On examination, blood pressure was 210/140 mmHg, pulse 92/min, regular. No pedal or generalized oedema was noted. Other systemic examinations showed mild pleural and pericardial effusion. The laboratory investigations showed hematuria, mild protenuria, elevated C-reactive protein, leucocytosis and raised erythrocyte sedimentation rate. Renal biochemical profile showed raised blood urea-89mg/dl, serum creatinine-2.5mg/dl, while other  parameters i.e electrolytes serum potassium-4.1 mEq/L, serum sodium-136 mEq/L were normal. The liver profile, thyroid profile  and coagulation study  were  within normal limits at presentation.
On the abdomino-pelvis sonography, left kidney measured 7.8 x 4.0 cm with an exophytic cortical solid mass having partially cystic areas at midpolar to hilar region. The mass measured 4.0 x 3.8 cm with septations. Right kidney measured 7.2 x 4.0 cm which was normal in size, shape and architecture. Urinary bladder was mildly dilated. Uterus showed intramural fibroid measuring 1.2 cm in maximum diameter. On sonography impression given was left renal mass  suggestive of renal neoplasm with cyst and hematoma.
MRI Abdomen and pelvis (plain) showed a well defined non encapsulated exophytic predominantly solid mass lesion measuring 4.3 x 4 x 4.5 cm. It was located in the anterior cortex of left kidney at interpolar region (Figure 1A, B). It was isointense on T1, hypointense on T2. The lesion was seen in close proximity of left renal vein with hilar lymph node enlargement. The venous thrombosis was absent. A bone scan revealed the absence of bone metastasis. Her Right kidney was normal. Other systemic evaluations showed  there was no evidence of any metastasis or any other malignancy. Other organs- urinary bladder, ovaries, liver, gall bladder, spleen, adrenals appeared normal. On MRI reported as malignant neoplastic lesion of left kidney likely to be renal cell carcinoma and  advised histopathological correlation.
Patient underwent left radical nephrectomy. No adjuvant chemotherapy or radiotherapy was provided. Our patient recovered well after nephrectomy and advised  follow up.
We received specimen of left radical nephrectomy along with  left renal hilar lymph nodes. On gross examination specimen of left radical nephrectomy totally measured 12 x 10.5 x 4.5 cm. A solid  mass at mid pole of kidney extending to the renal pelvis was noted. The cut section revealed a large, well circumscribed, lobulated, greyish white firm, fleshy tumor mass with focal areas of hemorrhage and necrosis (Figure 2). Tumor was totally measured  5.1 x 4 x 3 cm and solid area measured 2.3 x 2 cm. Cystic area was filled with blood and largest cyst measured 2.8 x 2 cm. The three left renal hilar lymph nodes were dissected, the largest measured 2.0 x 1.0 x 0.3 cm and smallest lymph node measured 1.8 x 1 x 1 cm. The cut section of which was  unremarkable.
On microscopy multiple sections were studied showed tumor composed of interlacing fascicles, whirling pattern and in sheets of neoplastic cells exhibiting spindle shaped morphology, mildly pleomorphic hyperchromatic vesicular nuclei with occasional nucleoli and eosinophilic fibrillar cytoplasm (Figure 3, 4, 5). Tumor showed increased mitotic figures (12/10 hpf). Tumor was infiltrating adjacent renal parenchyma. An areas of hemorrhage, necrosis was also evident. Adjacent renal parenchyma showed chronic interstitial nephritis, focal cyst formation and vascular proliferation. Renal capsule, pelvis perinephric fat, renal vessels, hilar lymph nodes and ureter were free from tumor. Microscopic features were of Malignant spindle cell tumor, histomorphology diagnosed as Primary Renal Sarcoma - Leiomyosarcoma. In our case tumor differentiation was - score 1 mitotic count score 2 (12 mitoses per 10 hpf, tumor necrosis - score 2, Histologic grade-2 total score (5) as per French Federation of Cancer Centers Sarcoma Group. The special stains were done which showed, Van Gieson's and Masson's trichrome staining confirmed a smooth muscle origin. Pathological TNM staging was T2N0M0 with a negative resection margins. The immunohistochemistry for confirmation and typing was done, which showed smooth muscle actin diffusely and desmin focally positive. The patient was thoroughly investigated for any primary sarcoma elsewhere. The final diagnosis of primary renal LMS was given. On follow up patient was asymptomatic and there was no evidence of any metastasis.
Figure 1 A, B. MRI Abdomen and pelvis (plain) shows a well defined non encapsulated solid mass in the anterior cortex of left kidney at interpolar region.
Figure 2. Left radical nephrectomy cut section showing a large, well circumscribed, lobulated, greyish white, firm , fleshy tumor mass with areas of necrosis and haemorrahges.
Figure 3. Photographmicrograph showing neoplastic spindle cells arranged in interlacing fascicles having pleomorphic nuclei with blunt ends and eosinophilic cytoplasm (Haematoxyline and eosin stain x40).
Figure 4. Tumor composed of neoplastic spindle cells having  pleomorphic, hyperchromatic nuclei with occasional nucleoli and eosinophilic fibrillar cytoplasm (Haematoxyline and eosin stain x100).
Figure 5. Spindle shape tumor cells with high cellularity, pleomorphic, hyperchromatic nuclei with occasional nucleoli and eosinophilic cytoplasm (Haematoxyline and eosin stain x400).
Discussion
The various malignant renal tumors of mesenchymal origin includes leiomyosarcoma, fibrosarcoma, liposarcoma, rhabdomyosarcoma, solitary fibrous tumor, malignant fibrous histiocytoma, osteosarcoma, synovial sarcoma and angiosarcoma.
Renal LMS are rare tumors of the kidney that were first reported by Berry in 1919 [3]. They comprise 0.5% to 1.5% of all malignant renal tumors in adults [4]. Prior to 1997, only 11 cases were reported in the English literature [5]. Improved diagnostic methods make current reports more frequent.
Primary sarcomas are rare in the kidney and represent 1%-2% of all malignant renal tumors  with only 0.12% of renal malignancies confirmed as leiomyosarcoma [6]. On histological subtype of renal sarcomas of pure mesenchymal origin, LMS is the most common variant accounting to 50-60%, followed by fibrosarcoma and liposarcoma. The renal LMS appear to arise from renal capsule or smooth muscle tissue of the vessels or renal pelvic wall [7, 8].

Analysis on the clinical examination data
Clinical  Presentation

On clinical presentation the symptoms are nonspecific and often overlap with other renal pathologies. The mean age at presentation is 50-60 years with a female preponderance. The cases may present with classic triad of symptoms as an abdominal mass, flank pain, and haematuria. Rare cases presenting with spontaneous retroperitoneal hemorrhage and hypotension have been reported. The cases of renal leiomyosarcoma presents clinically and radiographically as to the common renal malignancies. On radio imaging  computed tomography of renal sarcomas usually reveals a solid infiltrating mass as other  common renal malignancies [9].

Radio imaging evaluation

Advances in the imaging techniques have created great improvements in the diagnosis of renal cell carcinoma, however, renal is rare and does LMS not have known specific imaging characteristics. The computed tomography(CT) demonstrate imaging features usually reveals a solid infiltrating mass which is often very difficult to indistinguishable from renal sarcomas [10]. Due to this limitation, CT image-guided percutaneous renal mass biopsy is strongly recommended for histopathological diagnosis of the tumor with a high degree of diagnostic accuracy.
On CT renal sarcomas appearance is variable from solid masses, low attenuating to cystic. The renal LMS appear as expansile, heterogeneously-enhancing, and well-circumscribed solid masses that usually project exophytically from the kidney [11]. Large renal LMS may present as multilocular cystic masses with peripheral enhancement [9, 12].

Pathological findings

Usually renal LMS are larger in size when detected. Miller et al. observed the mean tumor size was 13.4?cm having a range from 4 to 26 cm [13]. The 60% of tumors are located on the right kidney.
On gross morphology, the tumor is well-circumscribed. On cut surface tumor show fleshy, grey white, whorled appearance with areas of haemorrhage necrosis and cystic degeneration.
The diagnosis is usually post-operative and requires a thorough sampling of the tumor. The careful evaluation for the site of tumor origin, histopathological type, its subtypes and to rule out an epithelial component especially to sarcomatoid renal cell carcinoma should be done. The common malignant renal neoplasms of  pure mesenchymal origin are LMS, fibrosarcoma and liposarcoma.
On microscopically, LMS show characteristics of smooth muscle tumor. The neoplastic cells are arranged in sheaths and fascicles of spindle shaped cells having blunt ended nuclei and mild to moderate amount of eosinophilic cytoplasm. The features of malignancy are tumor necrosis, nuclear pleomorphic nucleli, and increased mitotic figures (more than 1 mitoses/10 HPF).

Histopathological diagnosis and Differential diagnosis

According to the classification by the French Federation of Cancer Centers Sarcoma Group (FNCLCC) the pathological diagnosis and grade of the tumor was evaluated. The grade was scored based in the level of differentiation, presence of mitosis, and necrosis in each high power field [14]. The most of the renal LMS had significantly higher mitotic activity at the time of diagnosis(mean 8.6 mitoses/10 hpf), with most being FNCLCC grade 2 [15].
On histopathology the LMS has to be differentiated from sarcomatoid renal cell carcinoma, leiomyoma and renal angiomyolipoma [16, 17]. Retroperitoneal LMS, involving the kidney should be ruled out before making the diagnosis of primary renal LMS.
The low-grade LMS requires to be distinguished from a leiomyoma. In leiomyoma shows the fascicular arrangement of benign smooth muscles with no atypia the tumor cells lack of cytologic atypia and there is no necrosis. The mitotic activity is low i.e  0-1 mitoses/10 hpf.
In sarcomatoid variant of renal cell carcinoma shows a mixture of both epithelial and sarcomatoid components. The sarcomatous tumor cells are highly pleomorphic, with high mitotic activity. In tumor carefully look for any foci of classic renal cell carcinoma. Also the tumor morphologically lacks the alternating fascicles. Immunohistochemical positivity  for Keratin and EMA expression.
The epithelioid angiomyolipoma, a variant of angiomyolipoma, histologically can be mistaken for a LMS. The histological finding of mature adipose tissue with thick hyalinized blood vessels favors angiomyolipoma.
The other differential is primary monophasic synovial sarcoma of the kidney. It shows neoplastic spindle cells with hypercellular fascicular pattern, scant intervening stroma along with focal staghorn, branching vascular pattern. Also the fibrosarcoma and malignant peripheral nerve sheath tumor remains differential diagnosis.

Immunohistochemistry analysis

Leiomyosarcomas on immunohistochemical analysis showed that the tumor cells were diffusely positive for smooth muscle actin. Also express positivity for calponin, desmin, and H-caldesmon. Tumor are negative for cytokeratin, S-100 protein, and HMB45, CD117 and S-100.
In the sarcomatoid renal cell carcinoma, the epithelial markers CKAE1/AE3, EMA stain positive while the like smooth muscle actin, H-caldesmon, and desmin are negative [6, 18].
The Ki-67 proliferation index, and p16 and p53 tumor suppressor proteins are over-expressed in LMS, so it could be used as a prognostic marker.

Treatment for renal LMS

The currently recommended treatment for resectable tumors is complete surgical excision of the tumor with negative margins. Radical nephrectomy is the treatment of choice for primary  renal LMS [19]. The early and complete resection of the tumor  improve the overall prognosis. There is no consensus on the role of neoadjuvant or adjuvant radio/chemotherapy in the management of renal LMS [20]. Demir A, et al. observed that significant proportion of aggressive LMS that tend to recur locally, radical nephrectomy is a superior option that provides better oncologic control [21]. If the surgeon anticipates a grossly incomplete resection, intraoperative radiation therapy results in excellent local control and survival, with acceptable morbidity. Sharma et al. prescribed chemotherapy with mesna, adriamycin, ifosphamide and dacarbazine regimen and sandwich radiotherapy with a dose of 44 Gy/22#/4.5 weeks to the renal bed and adjoining lymphatics [22].
Novak M et al, stated that the neoadjuvant radiotherapy is generally administered while it is not indicated postoperatively in R0 (tumor resection with negative macro and microscopic margins) adjuvant chemotherapy is recommended in cases of R2 resections (tumors with positive macro and microscopic resection margins) as well as in unresectable and metastatic disease [20]. The regular follow-up  play important role in the treatment of renal LMS.

Prognosis

Dhamne SA et al. reported that the small tumor size (<5 cm), low histologic grade, and renal-limited disease are some favorable prognostic factors for LMS [23]. Kendal et al. reported the favorable prognostic markers are size < 4 cm, low grade, absence of nodal metastasis, and radical surgical treatment having favorable survival outcomes in the largest renal LMS cohort [1]. Novak M et al. observed that the renal LMS frequently metastasizes to distant body organs via hematogenous spread and carries an overall poor prognosis with a median overall survival of 25 months [20]. The distant metastases were identified in 90% of the patient primary LMS of the kidney in Miller et al study [13].
The study by Novak M et al. observed that the distant  metastasis  occurred in 30% of patients, local in 4.5%, while 15% of the patients experienced combined local recurrence and distant metastasis [20].
In Indians, renal primary leiomyosarcomas are represented mostly as case reports in the literature or as components of series of renal sarcomas as we summarized of recent cases in table 1 [24-37]. As primary renal leiomyosarcoma is an exceedingly uncommon tumor, advances in the techniques will be helpful for  improvements in the diagnosis and future plans.
Table 1. Summary of primary renal leiomyosarcoma in Indians (by Dr S V Jagtap , 2023).
S No. Author et al /Reference Year Patient Age (Years) Gender Main Clinical symptoms Renal Side Radioimaging USG/CT/MRI Gross Tumor Size (cm) Surgery Adjuveant Rx
1 Jagtap SV present study 2023 59 F hematuria, left-sided flank pain Left Renal Mass RCC 4.3x 4 x 4.5 Radical Nephrectomy No
2 Karri M [24] 2022 48 F Flank pain Right Renal Mass with peritoneal metastasis 7x5x4 Radical Nephrectomy No
3 Nandi S [25] 2021 68 F Abdominal pain Right Renal Mass 8x8x7 Radical Nephrectomy No
4 Jagtap SV [8] 2021 68 M Abdominal pain Hematuria Right Renal pelvis mass 3x1.9x2.4 Radical Nephrectomy No
5 Beigh A [26] 2018 35 M Flank Pain Right Renal Mass 12x5.5x4 Radical Nephrectomy No
6 65 F Hematuria Left Renal Mass 5x4x2.5 Radical Nephrectomy No
7 55 F Flank pain Left Renal Mass 7x4x2.4 Radical Nephrectomy No
8 64 M Flank pain Left Renal Mass 4x3x1 Radical Nephrectomy No
9 Kundu R [27] 2019 65 F Abdominal pain Left RCC 8x7x8 Radical Nephrectomy No
10 Malik A [28] 2017 50 F Flank pain Left RCC 8x4x2 Nephrectomy
11 Vasudevan S [29] 2016 57 F Flank pain Right RCC 22x15x10 Radical No
12 Rupali B [30] 2015 39 M Abdominal lump Left Renal Mass 16x14x12 Partial Nephrectomy No
13 Narula V [31] 2015 39 F Abdominal lump Right Renal Mass 11x7x6 Radical Nephrectomy No
14 Srivastav P [32] 2015 50 F Flank pain Left RCC - - -
15 Suresh B [33] 2014 65 F Abdominal lump Right Renal Mass 18x8x7 Nephrectomy No
16 Dhawan S [6] 2012 62 F Abdominal pain Left Retroperitoneal sarcoma 10x9x8 Radical Nephrectomy No
17 Suresh K [37] 2011 65 M Flank pain Right Renal mass - Radical Nephrectomy No
18 Bhat GS [34] 2011 68 M Abdominal pain Right Renal mass 5.6x5.1x5 Radical Nephrectomy No
19 Venkatesh K [35] 2010 55 F Abdominal mass Left Renal mass 20x16x12 Radical Nephrectomy No
20 Choudhury M [36] 2009 65 F Abdominal lump Right Renal exophytic mass 15x11x8 Radical Nephrectomy No
21 Dhamne S [23] 2009 60 M Increased frequency mituration Right Renal hilum pelvis mass 10x8x5.6 Radical Nephrectomy No
22 Sharma D [22] 2007 - - Flank pain Left RCC - Radical Nephrectomy Adjvent chemo and radiotherapy
RCC: Renal Cell Carcinoma, USG: ultrasonography, CT: computed tomography, MRI: Magnetic resonance imaging, Adjuvant Rx: Adjuvant treatment, M: male, F: female.
Conclusion
Primary leiomyosarcoma of the kidney is a rare renal mesenchymal tumor. These tumors does not have known specific imaging characteristics, so they should be differentiated from other renal malignancies on histopathological evaluation. The rarity of cases and absence of long-term follow up requires definitive treatment protocols.
Declaration

Acknowledgements

None.


Ethical policy

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. Approval from institutional ethical committee was taken.


Availability of data and materials

All data generated or analysed during this study are included in this publication.


Author contributions

SVJ carried out review of various articles and texts and them compiling, proof reading, editing and final drafting of manuscript. All authors contributed to the conception, case study, analysis, interpretation, drafting the work and substantively revising it.


Competing interests

All authors declare no competing interests.


Funding

None.

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Cite this article: Jagtap SV, Jagtap SS, Varshney K, Jadhav Y, Shah P: Primary Renal  Leiomyosarcoma: Case Report and Review of the Literature. Ann Urol Oncol 2022; 6(1): 32-38. https://doi.org/10.32948/auo.2023.01.28

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