- Case report
- Open access
- Published:
Myoid gonadal stromal tumor of the testis—the novel subtype of testicular gonadal stromal tumors: a case report and review of the literature
Journal of Medical Case Reports volume 18, Article number: 71 (2024)
Abstract
Background
Sex cord gonadal stromal tumors compose less than 10% of all testicular neoplasms and consist of a variety of histological subtypes. In 2016, the World Health Organization introduced a novel subtype, the myoid gonadal stromal tumor, that consists of spindle-shaped cells with immunohistologic features of muscle cells. Only few cases have been reported to date. Due to its rarity and owing to its only recent introduction, the current knowledge about myoid gonadal stromal tumor is limited, and particularly, appropriate clinical management is still ill-defined.
Case presentation
A 47-year-old man of Caucasian descent presented with nonspecific scrotal discomfort. A roundish and well demarcated hypoechoic mass of 8.5 mm in diameter was detected in the cranial region of the left testis. Serum tumor marker levels were within normal ranges. Testis-sparing surgery revealed a 9-mm whitish, hard mass with sharp surgical margin. Histologically, the neoplasm consisted of microfibrillar tissue with spindle-shaped cells harboring elongated nuclei. Immunohistochemical work-up disclosed expression of desmin, small muscle actin, and S100 protein giving evidence for the myogenic nature of the neoplastic cells. There was no indication of malignancy, neither histologically nor clinically. Follow-up of 1 year was uneventful.
Conclusion
A literature survey revealed 22 previous cases of myoid gonadal stromal tumor. The median age was 37 years, the median size of the neoplasm was 20 mm, and there was no side-preponderance. Myoid gonadal stromal tumor is not much different from other subtypes of gonadal stromal tumors nor from testicular gem cell tumors regarding age and laterality; however, tumor size is smaller in myoid gonadal stromal tumors than in germ cell tumors. Although rarely performed so far, testis-sparing surgery probably constitutes an appropriate treatment of this neoplasm. Myoid gonadal stromal tumor represents an emerging novel entity of benign testicular new growths that caregivers of patients with testicular tumors should be aware of.
Introduction
Testicular tumor is a rare disease with no more than 4100 cases arising annually in Germany [1]. Histologically, around 90% of testicular neoplasms comprise of germ cell tumors (GCTs), while the remainder is composed of a variety of rare neoplasms involving spermatocytic tumors, hematological neoplasms, sex cord gonadal stromal tumors, secondary malignancies, and others [2]. Sex cord gonadal stromal tumors comprise around 5–6% of all testicular neoplasms, most of which are of benign nature. Pathogenetically, these tumors are derived from tissue that originally formed the genital ridge during embryogenesis, which developed into the gonad by building the framework and seeding soil for the primordial germ cells invading from the yolk sac during the 4th to 6th week of gestation [3]. The most common neoplasm of this subgroup is the Leydig cell tumor, followed by several variants of Sertoli cell tumors [4, 5], Granulosa cell tumors [6, 7], mixed forms, tumors not otherwise specified (NOS), and extremely rare theca cell tumors [8]. Myoid gonadal stromal tumor (MGST) represents a newly recognized subtype among the sex cord gonadal stromal tumors. It is composed of cells sharing features of smooth muscle and of gonadal stroma as stated by the World Health Organization (WHO) expert team for classification of testicular tumors in 2016 [9]. The neoplasm is considered to derive from peritubular myofilaments or intertubular primitive mesenchymal cells. It is morphologically distinct from other sex cord gonadal stromal tumors [10], and it is characterized by spindle-shaped pale cells that are closely connected and surrounded by collagen layers [11]. Entrapping of seminiferous tubules by the neoplasm is considered to support the origin from peritubular structures. Immunohistochemical hallmarks are the expression of S100 protein, smooth muscle actin (SMA), and desmin.
Secondary to both its rarity and only very recent recognition as its own entity, the clinical features of MGST are still poorly understood, and no clear recommendations for treatment are available. Here, we report another case of MGST. In addition, a literature survey was performed to look for previously reported cases by searching the electronic data bases PubMed and Google Scholar and by hand-searching reference lists of previous reports. We discuss the clinical features of MGST in comparison with other testicular tumor entities.
Case presentation
A patient of Caucasian descent, aged 47 years, presented with unspecific left-sided scrotal discomfort lasting for several weeks. The right testicle had been excised for unknown reasons, presumably for undescended testis with congenital hernia, in early childhood. The patient was unmarried and childless. He reported a sedentary lifestyle due to his profession as a software-developer. Physical examination did not disclose any major pathological finding except for obesity (body mass index 33.1 kg/m2). The right sided scrotal contents was empty. The left testicle was normal sized but very touch sensitive; thus, a proper palpation was not feasible. Sonographically, a well demarcated hypoechoic roundish mass of 8.5 mm in diameter was detected (Fig. 1). Color-coded Duplex sonographic signals were present within the mass. Laboratory workup showed serum tumor markers alpha fetoprotein, beta human chorionic gonadotropin, and lactate dehydrogenase within normal limits; the same applied to white blood count, hemoglobin, retention parameters, and liver enzymes. Serum testosterone level was subnormal with 1.75 ng/ml [reference limits (RL) 2.4–7.8 ng/ml] at normal luteinizing hormone level [6.80 IU/l (RL 1.14–8.75 IU/l)]. Spermatogenetic parameters revealed seriously impaired fertility with a follicle stimulating hormone level of 18.71 IU/l (RL 0.95–11.95 IU/l) and an inhibin B of 10 ng/l (RL 120–400 ng/l). Based on the finding of a well-vascularized intratesticular mass upon ultrasonography, a testicular tumor was suspected. Accordingly, inguinal surgical exposure was performed with cord clamping and frozen-section-guided testis sparing excision (TSS) of the mass along with two marginal testicular biopsies, as recently advocated in a major review article [12].
On gross pathologic examination, the excised nodule consisted of a hard homogeneous mass of white-greyish color, sized 9 mm, with sharply demarcated surgical margin (Fig. 2). The adjacent testicular parenchyma was of normal brownish color and normal granular structure. Upon histological examination, the mass was homogeneously composed of microfibrillar tissue consisting of spindle-shaped cells with elongated nuclei (Fig. 3a). Immunohistologic examination revealed expression of desmin, SMA, and S100 but no expression of SOX10, inhibin, and calretinin (Fig. 3a–d). KI-67 proliferation index was < 1%. The marginal biopsies revealed atrophic testicular tissue with arrested spermatogenesis and focal Leydig cell hyperplasia but no germ cell neoplasia in situ. The final diagnosis was myoid gonadal stromal tumor.
The postoperative course was uneventful. Since no signs of malignancy had been found histologically and because computed tomography of chest and abdomen had not disclosed any abnormalities, no further treatment was administered. The patient was well and without local and distant recurrence 1 year after surgery.
Discussion
Following the formal recognition of myoid gonadal stromal tumors as its own entity by the WHO in 2016 [9], several cases published earlier in literature were retrospectively identified as neoplasms fulfilling the definition of MGST. The first case description is credited to Evans in 1977 [13]. The term myoid gonadal stromal stromal tumor was coined by Weidner in 1991 [14]. Additionally, another two cases with peritubular myofilament expression were documented by Greco et al. in 1984 [15].
To the best of our knowledge, a few more than 20 cases of myoid gonadal stromal tumors have been reported in literature to date. As stated earlier, a number of cases documented earlier would probably match the morphological definition of MGST outlined by the WHO in 2016 [9, 16], but in the absence of unequivocal pathohistological guidelines at the time of reporting and due to the lack of immunohistological techniques, these early cases will stay buried in literature. The cases reported thus far, along with their clinical features, are listed in Table 1 [10, 11, 13,14,15,16,17,18,19,20,21,22,23,24,25,26]. The median age of reported cases of MGST is 37 years with an interquartile range of 24 to 45 years. The median tumor size is 20 mm, with an interquartile range of 13–30 mm. There appears to be no side preponderance; because of 16 cases with information on laterality, 8 were right sided and 8 left sided. With respect to surgical treatment, all but one had full orchiectomy, while one had TSS; one case was without information.
With 47 years of age, our case belongs to one of the oldest patients with MGST, since only four of the hitherto reported cases were older. With respect to tumor size, the present case is one of the smallest. Only one of the reported cases had a smaller size (6 mm) [23]. Thus, the clinical features of our case are different from average characteristics of MGST but still within reported ranges. With respect to treatment, our patient underwent TSS. This conservative surgical approach had been performed in only one previous case [23]. In our case, the main reason for TSS was the tumor location in a solitary testis.
Table 2 provides a comparison of the clinical features of MGST as abstracted from Table 1 with those of three other types of gonadal stromal tumors [5, 6, 27] and of testicular GCTs [28, 29].
It becomes clear that MGST does well to compare with other benign tumors, such as Leydig cell tumors or Sertoli cell tumors, regarding median age, tumor size, and laterality. Also, germ cell tumors, seminomas, and nonseminomas are likewise not much different from MGST with respect to patient age. However, testicular GCTs apparently present with somewhat larger tumor sizes of 30–35 mm than MGSTs (median 20 mm). The rather small size of MGSTs may relate to the very slow growth rate as documented by the KI-67 index of < 1% opposed to KI-67 proliferation rates of 80–95% in GCTs.
Only the group of other malignant testicular neoplasms, such as malignant testicular lymphoma or secondary neoplasms (metastases), comprise markedly larger tumor sizes and older patient ages.
Histological diagnosis of MGST firstly relies on the presence of spindle-shaped cells presenting in a microfibrillar pattern. Secondly, immunohistological workup is needed to detect expression of S100 protein, smooth muscle actin (SMA), and desmin. The latter represents a specific intermediate filament protein that is essential for the structural integrity and function of muscle cells [30]. This immunohistochemical marker provided the final evidence for the myogenic differentiation of the mesenchymal cells that are present in this neoplasm. In contrast to most other gonadal stromal tumors [8], inhibin and calretinin are not necessarily expressed in MGST.
Preoperative diagnosis of MSGST is hardly possible because no specific symptoms prevail. Moreover, ultrasonographic findings are not specific for MGST. However, as shown in the present patient and several previously published cases, the testicular mass in MGST is usually roundish with clear margins. This finding is usually compatible with a benign tumor, particularly if the mass is small [31, 32]. TSS guided by frozen section examination can safely be performed in MGST, although the final diagnosis of this rare neoplasm will certainly be established only upon final immunohistochemical examination. In benign tumors, conservative surgery is principally feasible because no precursor cells of GCT (germ cell neoplasia in situ) are present in these testes, and thus, local recurrences are extremely rare. Testis-sparing surgery is particularly beneficial because testosterone deficiencies can be prevented in the later course. Therefore, this type of surgery is advocated by contemporary guidelines in all benign testicular neoplasms, unless the mass is multifocal or larger than 2 cm [33, 34]. In very small masses (< 5 mm), even surveillance without upfront surgery may be considered [35]. In view of the present knowledge about MGST, there is only little doubt about the benign nature of this neoplasm, and thus, a conservative surgical procedure is clearly justified.
Because of the rarity of benign testicular tumors, contemporary guidelines do not give clear recommendations regarding follow-up. Based on the cumulative experience regarding the clinical management of benign testicular tumors, an annual follow-up examination, including scrotal sonography, appears reasonable [33, 36].
Conclusion
Myoid gonadal stromal tumors represent an emerging new entity of benign testicular gonadal stromal tumors. Immunohistological hallmarks are the expression of desmin, smooth muscle actin, and S100 protein. The clinical characteristics are not much different from those of other benign testicular neoplasms. Testis-sparing surgery appears to be the treatment of choice.
Availability of data and materials
Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. All clinical data presented in the manuscript are available from the corresponding author upon reasonable request.
Abbreviations
- MGST:
-
Myoid gonadal stromal tumor
- GCT:
-
Germ cell tumor
- IU:
-
International units
- IQR:
-
Inter quartile range
- NOS:
-
Not otherwise specified
- RL:
-
Reference limit
- SMA:
-
Small muscle actin
- TSS:
-
Testis-sparing surgery
- WHO:
-
World Health Organization
References
Brandt MP, Gust KM, Bon D, Tsaur I, Thomas C, Neisius A, Haferkamp A, Herrmann E, Bartsch G. Trend analysis and regional tumor incidence in Germany for testicular cancer between 2003 and 2014. Andrology. 2019;7(4):408–14.
Mikuz G. Update on the pathology of testicular tumors. Anal Quant Cytopathol Histpathol. 2015;37(1):75–85.
Young RH. Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems. Mod Pathol. 2005;18(Suppl 2):S81–98.
Angerer M, Wülfing C, Gübitz R, Harms A, Dieckmann KP. Unilateral, small, benign, late-onset, large-cell calcifying sertoli cell tumor: a case report. Cureus. 2023;15(7): e41614. https://doi.org/10.7759/cureus.41614.
Grogg J, Schneider K, Bode PK, Kranzbühler B, Eberli D, Sulser T, Lorch A, Beyer J, Hermanns T, Fankhauser CD. Sertoli cell tumors of the testes: systematic literature review and meta-analysis of outcomes in 435 patients. Oncologist. 2020;25(7):585–90.
Dieckmann KP, Bertolini J, Wülfing C. Adult granulosa cell tumor of the testis: a case report with a review of the literature. Case Rep Urol. 2019;5:7156154. https://doi.org/10.1155/2019/7156154.
Grogg JB, Schneider K, Bode PK, Kranzbühler B, Eberli D, Sulser T, Beyer J, Lorch A, Hermanns T, Fankhauser CD. Risk factors and treatment outcomes of 239 patients with testicular granulosa cell tumors: a systematic review of published case series data. J Cancer Res Clin Oncol. 2020;146(11):2829–41. https://doi.org/10.1007/s00432-020-03326-3.
Bremmer F, Behnes CL, Radzun HJ, Bettstetter M, Schweyer S. Sex cord gonadal stromal tumors. Pathologe. 2014;35(3):245–51 (Article in German).
Idrees MT, Ulbright TM, Oliva E, Young RH, Montironi R, Egevad L, Berney D, Srigley JR, Epstein JI, Members of the International Society of Urological Pathology Testicular tumor Panel. The World Health Organization 2016 classification of testicular non-germ cell tumors: a review and update from the International Society of Urological Pathology Testis Consultation Panel. Histopathology. 2017;70(4):513–21.
Kao CS, Ulbright TM. Myoid gonadal stromal tumor: a clinicopathologic study of three cases of a distinctive testicular tumor. Am J Clin Pathol. 2014;142(5):675–82. https://doi.org/10.1309/AJCPGSCD1DGNZ0QO.
Renne SL, Valeri M, Tosoni A, Bertolotti A, Rossi R, Renne G, Colecchia M. Myoid gonadal tumor. Case series, systematic review, and Bayesian analysis. Virchows Arch. 2021;478(4):727–34. https://doi.org/10.1007/s00428-020-02957-8.
García Rojo E, Giannarini G, García Gómez B, Feltes Ochoa JA, Guerrero Ramos F, Alonso Isa M, Brime Menendez R, Saenz Calzada DM, Justo Quintas J, Fraile A, et al. Organ-sparing surgery for testicular germ cell tumors: a current perspective. Medicina. 2023;59(7):1249. https://doi.org/10.3390/medicina59071249.
Evans HL. Unusual gonadal stromal tumor of the testis. Case report with ultrastructural observations. Arch Pathol Lab Med. 1977;101(6):317–20.
Weidner N. Myoid gonadal stromal tumor with epithelial differentiation (? testicular myoepithelioma). Ultrastruct Pathol. 1991;15(4–5):409–16. https://doi.org/10.3109/01913129109016248.
Greco MA, Feiner HD, Theil KS, Mufarrij AA. Testicular stromal tumor with myofilaments: ultrastructural comparison with normal gonadal stroma. Hum Pathol. 1984;15(3):238–43. https://doi.org/10.1016/S0046-8177(84)80186-0.
Colecchia M, Bremmer F, Pini GM. News in the classification of WHO 2022 testicular tumors. Pathologica. 2023;115(1):3–7. https://doi.org/10.32074/31591-32951X-32825.
Miettinen M, Salo J, Virtanen I. Testicular stromal tumor: ultrastructural, immunohistochemical, and gel electrophoretic evidence of epithelial differentiation. Ultrastruct Pathol. 1986;10(6):515–28. https://doi.org/10.3109/01913128609007209.
Allen PR, King AR, Sage MD, Sorrell VF. A benign gonadal stromal tumor of the testis of spindle fibroblastic type. Pathology. 1990;22(4):227–9. https://doi.org/10.3109/00313029009086667.
Nistal M, Puras A, Perna C, Guarch R, Paniagua R. Fusocellular gonadal stromal tumor of the testis with epithelial and myoid differentiation. Histopathology. 1996;29(3):259–64. https://doi.org/10.1111/j.1365-2559.1996.tb01400.x.
Renshaw AA, Gordon M, Corless CL. Immunohistochemistry of unclassified sex cord-stromal tumors of the testis with a predominance of spindle cells. Mod Pathol. 1997;10(7):693–700.
Magro G, Gurrera A, Gangemi P, Saita A, Greco P. Incompletely differentiated (unclassified) sex cord/gonadal stromal tumor of the testis with a “pure” spindle cell component: report of a case with diagnostic and histogenetic considerations. Pathol Res Pract. 2007;203(10):759–62. https://doi.org/10.1016/j.prp.2007.05.011.
Du S, Powell J, Hii A, Weidner N. Myoid gonadal stromal tumor: a distinct testicular tumor with peritubular myoid cell differentiation. Hum Pathol. 2012;43(1):144–9. https://doi.org/10.1016/j.humpath.2011.04.017.
Ercolino A, Manes F, Vasuri F, Bianchi L, Garofalo M, Piazza P, Corcioni B, Schiavina R, Golfieri R, Fiorentino M, et al. A case report of myoid gonadal stromal tumor treated with testis sparing surgery. Transl Androl Urol. 2022;11(10):1458–65. https://doi.org/10.21037/tau-22-179.
D’Abbronzo G, Ronchi A, Belfiore MP, Mantia E, Feroce F, Pignata S, Perdonà S, Franco R. Myoid gonadal stromal tumor, a case report with review of the literature. Indian J Pathol Microbiol. 2022;65(2):444–7. https://doi.org/10.4103/0377-4929.343206.
Madendere S, Kılıç M, Yıldırım H, Ekemen S, Yıldız DK, Balbay MD. Preoperative magnetic resonance imaging cannot predict the presence of a rare myoid gonadal stromal testicular tumor: a case report. Urol Int. 2023;107:823–6. https://doi.org/10.1159/000531121.
Elousrouti LT, Gouzi I, Hammas N, Chbani L, Tazi F, Fareh MH, Elfatemi H. Myoid gonadal stromal tumor: a new case report with a review of the literature. Int J Surg Pathol. 2023. https://doi.org/10.1177/10668969231160256.
Ruf CG, Sanatgar N, Isbarn H, Ruf B, Simon J, Fankhauser CD, Dieckmann KP. Leydig-cell tumor of the testis: retrospective analysis of clinical and therapeutic features in 204 cases. World J Urol. 2020;38(11):2857–62. https://doi.org/10.1007/s00345-020-03079-1.
Dieckmann KP, Isbarn H, Grobelny F, Dumlupinar C, Utschig J, Wülfing C, Pichlmeier U, Belge G. Testicular neoplasms: primary tumor size is closely interrelated with histology, clinical staging, and tumor marker expression rates—a comprehensive statistical analysis. Cancers (Basel). 2022;14(21):5447. https://doi.org/10.3390/cancers14215447.
Dieckmann KP, Richter-Simonsen H, Kulejewski M, Ikogho R, Zecha H, Anheuser P, Pichlmeier U. Testicular germ-cell tumors: a descriptive analysis of clinical characteristics at first presentation. Urol Int. 2018;100(4):409–19.
Paulin D, Li Z. Desmin: a major intermediate filament protein essential for the structural integrity and function of muscle. Exp Cell Res. 2004;301(1):1–7. https://doi.org/10.1016/j.yexcr.2004.1008.1004.
Bertolotto M, Muça M, Currò F, Bucci S, Rocher L, Cova MA. Multiparametric US for scrotal diseases. Abdom Radiol. 2018;43(4):899–917. https://doi.org/10.1007/s00261-018-1510-7.
Ager M, Donegan S, Boeri L, Mayor de Castro J, Donaldson JF, Omar MI, Dimitropoulos K, Tharakan T, Janisch F, Muilwijk T, et al. Radiological features characterising indeterminate testes masses; a systematic review and meta-analysis. BJU Int. 2022;131(3):288–300. https://doi.org/10.1111/bju.15869.
Staudacher N, Tulchiner G, Bates K, Ladurner M, Kafka M, Aigner F, Pichler R, Horninger W. Organ-sparing surgery in testicular tumor: is this the right approach for lesions ≤ 20 mm? J Clin Med. 2020;9(9):E2911. https://doi.org/10.3390/jcm9092911.
Kliesch S, Schmidt S, Wilborn D, Aigner C, Albrecht W, Bedke J, Beintker M, Beyersdorff D, Bokemeyer C, Busch J, et al. Management of germ cell tumors of the testes in adult patients: German clinical practice guideline, part II—recommendations for the treatment of advanced, recurrent, and refractory disease and extragonadal and sex cord/stromal tumors and for the management of follow-up, toxicity, quality of life, palliative care, and supportive therapy. Urol Int. 2021;105(3–4):181–91.
Bertolotto M, Campo I, Pavan N, Buoite Stella A, Cantisani V, Drudi FM, Cova MA, Derchi LE. What is the malignant potential of small (<2 cm), nonpalpable testicular incidentalomas in adults? A systematic review. Eur Urol Focus. 2023;9(2):361–70. https://doi.org/10.1016/j.euf.2022.10.001.
Raison N, Warrington J, Alnajjar HM, Muneer A, Ahmed K. The role of partial orchidectomy in the management of small testicular tumors: fertility and endocrine function. Andrology. 2020;8(5):988–95.
Acknowledgements
The authors are grateful to the patient for giving his permission to analyze and publish details of his clinical case.
Funding
The present work did not receive any funding.
Author information
Authors and Affiliations
Contributions
Conceptualization: KPD and MA; methodology: KPD, MA, and CW; formal analysis and investigation: LT and AH; writing—first draft: KPD and LT; writing—review and editing: KPD, LT, MA, AH, and CW; supervision: CW. All authors have approved the submitted version of the manuscript. All authors have agreed both to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in literature.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
As the identity of the patient reported herein remained fully undisclosed, no formal ethical approval was required. All activities related to this report were conducted in accordance with the Declaration of Helsinki of the World Medical Association, amended by the 64th General Assembly in October 2013.
Consent for publication
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Competing interests
The authors declare that they have no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Dieckmann, KP., Tharun, L., Angerer, M. et al. Myoid gonadal stromal tumor of the testis—the novel subtype of testicular gonadal stromal tumors: a case report and review of the literature. J Med Case Reports 18, 71 (2024). https://doi.org/10.1186/s13256-024-04393-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s13256-024-04393-7