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Signet-ring stromal tumor of the testis: a case report and literature review
Human Pathology (2009) 40, 584–587
www.elsevier.com/locate/humpath
Case study
Signet-ring stromal tumor of the testis: a case report and literature review Chen Yun Kuo MD a , Mei Chin Wen MD a,b , John Wang MD, PhD a,b , Yee Jee Jan MD a,b,⁎ a
Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan College of Medicine and College of Nursing, Hungkuang University, Taichung, Taiwan
b
Received 24 April 2008; revised 7 July 2008; accepted 14 July 2008
Keywords: Signet-ring stromal tumor, SRST; Testis; Ovary
Summary Primary signet-ring stromal tumor of the testis is extremely rare. To our knowledge, only one case has been reported in the literature. Herein, we present a case of testicular signet-ring stromal tumor with positive immunostain for CD99, which has not been reported previously. We also review the literature and discuss the clinicopathological significance of this type of tumor. The most important differential diagnosis of signet-ring stromal tumor is metastatic signet-ring cell carcinoma because of its different management and prognosis. Fortunately, signet-ring stromal tumors have a well-defined growth pattern, bland histological features, no mucin production, and immunoreaction to vimentin rather than cytokeratin, all of which help pathologists to rule out metastatic adenocarcinoma. Although ovarian signet-ring stromal tumors are categorized in the fibroma/thecoma group of sex cord stromal tumors, the cell origin of signet-ring stromal tumors is still debatable. The histological criteria for predicting clinical behavior of signet-ring stromal tumors are not clear. Fortunately, however, all reported signet-ring stromal tumors are benign tumors with excellent prognosis, and they do not recur or metastasize. We consider signet-ring stromal tumor to be a special type of sex cord stromal tumor. © 2009 Elsevier Inc. All rights reserved.
1. Introduction
2. Case report
Ramzy [1] first described signet-ring stromal tumor (SRST) of the ovary in 1976. Since then, only 9 more ovarian cases have been reported [1-6]. Michal et al [7] reported the first case of testicular SRST in 2005. Herein, we present a case of testicular SRST. We also review the literature and discuss the clinicopathological significance of this type of tumor.
A 33-year-old man incidentally found a nodular mass in his left testis. Imaging studies revealed a T1 isosignal intensity and T2 hyposignal intensity nodular mass with strong enhancement at the left upper testicle and a hypoechoic and hypovascular mass with ring calcification and casting shadow on sonography. Serologically, neither human chorionic gonadotropin nor α-fetoprotein was elevated. The tumor was totally resected by partial orchiectomy with complete tumor excision thereafter. A tan-colored nodular mass, 0.7 cm in diameter, elastic in consistency with a homogeneous tan-gray cut surface, was excised. Microscopically, this tumor was well circumscribed with an inconspicuous fibrous capsule and
⁎ Corresponding author. Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan. E-mail address: [email protected] (Y. J. Jan). 0046-8177/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2008.07.012
Signet-ring stromal tumor of the testis surrounded by atrophic seminiferous tubules (Fig. 1A). The tumor was composed of epithelioid round cells arranged in single cells, cords, and nests separated by collagen bundles (Fig. 1B). These round cells had roundto-oval nuclei with distinct nucleoli and evenly dispersed fine chromatin. The cytoplasm was pale and granular with
585 variable-sized vacuoles. Many cells had single large cytoplasmic vacuoles that pushed the nuclei to the periphery and showed a signet-ring cell feature (Fig. 1C). Scattered eosinophilic globules could be seen in the cytoplasm (Fig. 1D). No tumor necrosis, nuclear atypia or mitotic figure was found.
Fig. 1 A, The tumor is well-circumscribed with an inconspicuous fibrous capsule and surrounded by atrophic seminiferous tubules (hematoxylin-eosin [H&E] stain ×40). B, Tumor is composed of epithelioid round cells in vague cords and small nests separated by collagen fibers, mimicking a metastatic adenocarcinoma (H&E stain ×100). C, Tumor cells have round-to-oval nuclei with small distinct nucleoli and fine, regularly dispersed chromatin. Pale granular cytoplasm with variable-sized vacuoles pushed nuclei to the periphery and displayed a signet-ring feature (H&E stain ×400). D, A few intracytoplasmic eosinophilic hyaline globules can be seen. These eosinophilic globules resemble extracellular collagen bundles (H&E stain ×1000). E and F, Tumor cells were immunoreactive for vimentin (E) and CD99 (F).
Excellent Excellent Excellent Excellent Excellent 1y 4.7 y 1 mo 3y 2 mo
Excellent Excellent 2m 2y
1.5 y
Left 5 Right 3.5 Right 13 Right 1 Left 0.7 Ovary Ovary Ovary Testis Testis Michal et al Kuo et al
2003 8 2004 9 10 2005 11 2008 12 Su et al Vang et al
8.9 2.5 Ovary N/A Ovary Left Cashell et al
6 2000 7
8.5 N/A Ovary N/A 5
Abbreviations: BSO, bilateral salpingo-oophorectomy; HS, hysterectomy; IHC, immunohistochemical; N/A, not available; PO, partial orchiectomy; RSO, right salpingo-oophorectomy; SMA, smooth muscle actin.
N/A Vimentin Vimentin Vimentin Monophasic Biphasic Monophasic Monophasic
None None None Cystic teratoma in ipsilateral ovary None Abdominal pain Abdominal pain Pelvic mass N/A Right 8 Left 9 Left 13 N/A 5 Ovary Ovary Ovary Ovary Ramzy 1976 1 Suarez et al 1993 2 Dickersin et al 1995 3 4
Histology Combined tumor Size Symptom (cm) No. Organ Side Year Author
Summary of clinical and histopathological features of SRST Table 1
A clinicopathological summary of all SRSTs reported in the literature is listed in Table 1. Clinically, patients with SRSTs of the ovary have abdominal pain, pelvic mass, or weight loss [1-6]. Testicular SRSTs are asymptomatic [7]. All SRSTs are unilateral and confined to the ovary or testis [1-7]. Except for 1 SRST reported in conjunction with Brenner tumor [4] and 1 SRST associated with cystic teratoma [3], all other reported SRSTs were solitary tumors. Grossly, SRSTs of the ovary are larger (mean size, 7.6 cm) than those of the testis (mean size, 0.9 cm). All SRSTs show benign behavior with excellent prognosis, and they do not recur or metastasize. Histopathologically, two distinct patterns of SRSTs are commonly observed. Some tumors are monophasic, composed of round, epithelioid cells separated by fibrous septa [1,3,4,7], and others show biphasic growth of round epithelioid cells and spindle cells [2,3,5,6]. All SRSTs have characteristic cytoplasmic vacuoles with an obvious signet-ring feature. These clear vacuoles contain no mucin or glycogen. One reported case was positive for neutral lipids in vacuolated and spindle cells by Oil red O staining [3]. Several cases revealed eosinophilic intracytoplasmic globules [1-3,6]. Immunohistochemically, all cases stained positive for vimentin [2-4,6,7]. Tumor cells also were variably positive for keratin, smooth muscle actin, or inhibin [3,4]. Immunohistochemical markers for sex-cord stromal neoplasms, such as calretinin, inhibin, CD99, and CD56, were stained in our case, but tumor cells were only immunoreactive for CD99. Ultrastructural studies for ovarian SRSTs reveal the diverse pathogenesis of the signet-ring feature. Ramzy found proteinaceous material both inside the vacuoles and in the intercellular matrix, which was moderately electrondense and flocculent with some fibrillary structures. He postulated that the signet-ring cell stromal tumor probably represents a separate tumor entity rather than a variant of the sclerosing stromal tumor [1]. Suarez et al [2] observed the intracytoplasmic eosinophilic globules and suggested these vacuoles were caused by globule elimination. Dickersin et al [3] studied 4 cases and concluded than there were 3 different
Positive IHC stains
3. Discussion
Monophasic Vimentin, keratins (AE1.3/AE3, N/A CAM5.2, wide spectrum), SMA N/A None Biphasic Vimentin, SMA N/A Weight loss Mixed with Brenner Monophasic Vimentin, SMA, inhibin A HS and BSO tumor Abdominal pain None Biphasic N/A BSO Pelvic mass None Monophasic Vimentin Oophorectomy Abdominal pain None Biphasic Vimentin HS and BSO N/A None Monophasic Vimentin Tumor excision Asymptomatic None Monophasic Vimentin, CD99 PO
16 mo 2y 17.4 y 2y HS and RSO Oophorectomy HS and BSO N/A
Treatment
Follow-up Prognosis
These vacuoles revealed neither mucin nor glycogen content on mucicarmine and periodic acid-Schiff stains. Immunohistochemically, the tumor cells reacted to vimentin (Fig. 1E) and CD99 (Fig. 1F) but were negative for AE1/ AE3, epithelial membrane antigen, estrogen receptor, progesterone receptor, calretinin, placenta-like alkaline phosphatase, inhibin-α, smooth muscle actin, desmin, S100 protein, bcl-2, CD246, CD31, CD34, CD56, and CD68. No recurrence or metastasis of this tumor was noted after 1 month follow-up.
Excellent
C. Y. Kuo et al. Excellent Excellent Excellent Excellent
586
Signet-ring stromal tumor of the testis mechanisms of signet-ring cell formation: generalized edema of cytoplasmic matrix, dilation of mitochondria in mitochondria-rich cells, and invagination of the cell membrane by the extracellular matrix. Cashell et al [4] found that many vacuoles were surrounded by a single membrane, but a few vacuoles were formed by swollen mitochondria. None of these cases showed desmosome or basement membrane formation supporting the mesenchymal origin. Based on histological, immunohistochemical, and ultrastructural study, SRSTs of the ovary are categorized in the fibroma/thecoma group of sex-cord stromal tumors by the World Health Organization [8]. We believe the SRST of the testis is identical to its ovarian counterpart and belongs to the category of sex cord stromal tumor [9,10]; however, whether it should be classified as one type of fibroma/ thecoma is still debatable. The Sertoli cell tumor often has cytoplasmic vacuoles and a nested and cord-like pattern, and the immunohistochemical studies of our case are consistent with Sertoli cell tumor. In our opinion, SRST is probably a specific variant of Sertoli cell tumor with unique histological features and distinct clinical behavior. It is important to differentiate SRST from other sex-cord stromal tumors and have a clear criterion to define SRST because other sex cord stromal tumors may have similar signet-ring cells. In one study, the proportion of signet-ring cell components in ovarian SRST ranged from 20% to 70% [6]. Irving et al [11] claimed that the term “SRST” is best reserved for tumors consisting of a significant proportion of signet-ring cells. The differential diagnosis of SRST and metastatic signetring cell carcinoma is crucial because both types of tumors have a distinct prognosis and treatment. Although rarer than metastasis to the ovary, metastatic signet-ring cell carcinomas to the testicles have been reported [12]. The welldefined growth patterns, mild cellular pleomorphism, and zero-to-low mitotic rate all indicate the benign nature of SRSTs. Unlike signet-ring cell carcinomas, SRSTs do not secrete mucin. The immunoreaction to vimentin rather than cytokeratin or epithelial membrane antigen also helps rule out metastatic carcinoma [6]. In the testis and ovary, adenomatoid tumors may consist of well-defined fibrous nodules with epithelioid tumor cells arranged in single cells, cords, and nests separated by collagen bundles. However, tumor cells of adenomatoid tumors have a glandular or tubular structure and react to mesothelial cell markers. Although very rare, epithelioid hemangioendotheliomas of the testis have been reported [13]. Histologically, epithelioid hemangioendotheliomas show solid nests and short cords of rounded or slightly spindled endothelial cells with intracytoplasmic lumens or vacuoles. This feature mimics signet-ring cells. Unlike SRSTs, intracytoplasmic lumens of epithelial hemangioendotheliomas usually contain erythrocytes, and these epithelioid endothelial cells express endothelial markers such as CD31 and CD34. In the testis, although the distinction of Leydig cell tumors and SRSTs is not critical because both tumors lack
587 malignant features, Leydig cell tumors should be included in the differential diagnosis because Leydig cell tumors with lipomatous changes consisting of vacuolated or foamy cells resemble signet-ring cells [9]. The Reinke crystals, lipid content of vacuoles, and intense immunoreactivity for inhibin of Leydig cell tumors are different from SRSTs. Luteinized thecomas histologically have luteinized cells with vacuolated cytoplasm dispersed among the spindle-shaped cells and may be confused with SRSTs. Unlike thecoma, most SRSTs are negative for inhibin immunohistochemically and contain no lipids in vacuoles. Partial orchiectomy with complete tumor excision may be adequate treatment for SRSTs. In our case, neither recurrence nor metastasis was noted after partial orchiectomy and preservation of the residual normal testis, which may be important for fertility. However, because ovarian SRSTs are clinically symptomatic and larger at presentation, they may require oophorectomy.
References [1] Ramzy I. Signet-ring stromal tumor of ovary. Histochemical, light, and electron microscopic study. Cancer 1976;38:166-72. [2] Suarez A, Palacios J, Burgos E, Gamallo C. Signet-ring stromal tumor of the ovary: a histochemical immunohistochemical and ultrastructural study. Virchows Arch A Pathol Anat Histopathol 1993; 422:333-6. [3] Dickersin GR, Young RH, Scully RE. Signet-ring stromal and related tumors of the ovary. Ultrastruct Pathol 1995;9:401-19. [4] Cashell AW, Jerome WG, Flores E. Signet ring stromal tumor of ovary occurring in conjunction with Brenner tumor. Gynecol Oncol 2000;77: 323-6. [5] Su RM, Chang KC, Chou CY. Signet-ring stromal tumor of the ovary: a case report. Int J Gynecol Cancer 2003;13:90-3. [6] Vang R, Bague S, Tavassoli FA, Prat J. Signet-ring stromal tumor of the ovary: clinicopathologic analysis and comparison with Krukenberg tumor. Int J Gynecol Pathol 2004;23:45-51. [7] Michal M, Hes O, Kazakov DV. Primary signet-ring stromal tumor of the testis. Virchows Arch 2005;447:107-10. [8] Tavassoli FA, Mooney E, Gersell DJ, et al. Sex cord-stromal tumours. In: Tavassoli FA, Devilee P, editors. World Health Organization classification of tumours: tumours of the breast and female genital organs. Lyon: IARC Press; 2003. p. 146-61. [9] Sesterhenn IA, Cheville J, Woodward PJ, et al. Sex cord / gonadal stromal tumours. In: Eble JN, et al, editor. World Health Organization classification of tumours: tumours of the urinary system and male genital organs. Lyon: IARC Press; 2004. p. 250-8. [10] Sex cord-stromal tumors. In: Ulbright TM, Amin MB, Young RH, editors. Atlas of tumor pathology. Tumors of the testis, adnexa, spermatic cord, and scrotum. Washington, D.C.: Armed Forces Institute of Pathology; 1999. p. 193-233. [11] Irving JA, McCluggage WG. Ovarian spindle cell lesions: a review with emphasis on recent developments and differential diagnosis. Adv Anat Pathol 2007;14:305-19. [12] Niesel T, Bohm J, Paul R, Breul J, Hartung R. Rare metastases of signet ring cell carcinomas to the scrotum: report of two cases. Urology 1996;47:769-71. [13] Tsolos C, Polychronidis A, Sivridis E, Kelidis G, Simopoulos C. Epithelioid hemangioendothelioma of the testis. J Urol 2001;166: 1834.
www.elsevier.com/locate/humpath
Case study
Signet-ring stromal tumor of the testis: a case report and literature review Chen Yun Kuo MD a , Mei Chin Wen MD a,b , John Wang MD, PhD a,b , Yee Jee Jan MD a,b,⁎ a
Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan College of Medicine and College of Nursing, Hungkuang University, Taichung, Taiwan
b
Received 24 April 2008; revised 7 July 2008; accepted 14 July 2008
Keywords: Signet-ring stromal tumor, SRST; Testis; Ovary
Summary Primary signet-ring stromal tumor of the testis is extremely rare. To our knowledge, only one case has been reported in the literature. Herein, we present a case of testicular signet-ring stromal tumor with positive immunostain for CD99, which has not been reported previously. We also review the literature and discuss the clinicopathological significance of this type of tumor. The most important differential diagnosis of signet-ring stromal tumor is metastatic signet-ring cell carcinoma because of its different management and prognosis. Fortunately, signet-ring stromal tumors have a well-defined growth pattern, bland histological features, no mucin production, and immunoreaction to vimentin rather than cytokeratin, all of which help pathologists to rule out metastatic adenocarcinoma. Although ovarian signet-ring stromal tumors are categorized in the fibroma/thecoma group of sex cord stromal tumors, the cell origin of signet-ring stromal tumors is still debatable. The histological criteria for predicting clinical behavior of signet-ring stromal tumors are not clear. Fortunately, however, all reported signet-ring stromal tumors are benign tumors with excellent prognosis, and they do not recur or metastasize. We consider signet-ring stromal tumor to be a special type of sex cord stromal tumor. © 2009 Elsevier Inc. All rights reserved.
1. Introduction
2. Case report
Ramzy [1] first described signet-ring stromal tumor (SRST) of the ovary in 1976. Since then, only 9 more ovarian cases have been reported [1-6]. Michal et al [7] reported the first case of testicular SRST in 2005. Herein, we present a case of testicular SRST. We also review the literature and discuss the clinicopathological significance of this type of tumor.
A 33-year-old man incidentally found a nodular mass in his left testis. Imaging studies revealed a T1 isosignal intensity and T2 hyposignal intensity nodular mass with strong enhancement at the left upper testicle and a hypoechoic and hypovascular mass with ring calcification and casting shadow on sonography. Serologically, neither human chorionic gonadotropin nor α-fetoprotein was elevated. The tumor was totally resected by partial orchiectomy with complete tumor excision thereafter. A tan-colored nodular mass, 0.7 cm in diameter, elastic in consistency with a homogeneous tan-gray cut surface, was excised. Microscopically, this tumor was well circumscribed with an inconspicuous fibrous capsule and
⁎ Corresponding author. Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan. E-mail address: [email protected] (Y. J. Jan). 0046-8177/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2008.07.012
Signet-ring stromal tumor of the testis surrounded by atrophic seminiferous tubules (Fig. 1A). The tumor was composed of epithelioid round cells arranged in single cells, cords, and nests separated by collagen bundles (Fig. 1B). These round cells had roundto-oval nuclei with distinct nucleoli and evenly dispersed fine chromatin. The cytoplasm was pale and granular with
585 variable-sized vacuoles. Many cells had single large cytoplasmic vacuoles that pushed the nuclei to the periphery and showed a signet-ring cell feature (Fig. 1C). Scattered eosinophilic globules could be seen in the cytoplasm (Fig. 1D). No tumor necrosis, nuclear atypia or mitotic figure was found.
Fig. 1 A, The tumor is well-circumscribed with an inconspicuous fibrous capsule and surrounded by atrophic seminiferous tubules (hematoxylin-eosin [H&E] stain ×40). B, Tumor is composed of epithelioid round cells in vague cords and small nests separated by collagen fibers, mimicking a metastatic adenocarcinoma (H&E stain ×100). C, Tumor cells have round-to-oval nuclei with small distinct nucleoli and fine, regularly dispersed chromatin. Pale granular cytoplasm with variable-sized vacuoles pushed nuclei to the periphery and displayed a signet-ring feature (H&E stain ×400). D, A few intracytoplasmic eosinophilic hyaline globules can be seen. These eosinophilic globules resemble extracellular collagen bundles (H&E stain ×1000). E and F, Tumor cells were immunoreactive for vimentin (E) and CD99 (F).
Excellent Excellent Excellent Excellent Excellent 1y 4.7 y 1 mo 3y 2 mo
Excellent Excellent 2m 2y
1.5 y
Left 5 Right 3.5 Right 13 Right 1 Left 0.7 Ovary Ovary Ovary Testis Testis Michal et al Kuo et al
2003 8 2004 9 10 2005 11 2008 12 Su et al Vang et al
8.9 2.5 Ovary N/A Ovary Left Cashell et al
6 2000 7
8.5 N/A Ovary N/A 5
Abbreviations: BSO, bilateral salpingo-oophorectomy; HS, hysterectomy; IHC, immunohistochemical; N/A, not available; PO, partial orchiectomy; RSO, right salpingo-oophorectomy; SMA, smooth muscle actin.
N/A Vimentin Vimentin Vimentin Monophasic Biphasic Monophasic Monophasic
None None None Cystic teratoma in ipsilateral ovary None Abdominal pain Abdominal pain Pelvic mass N/A Right 8 Left 9 Left 13 N/A 5 Ovary Ovary Ovary Ovary Ramzy 1976 1 Suarez et al 1993 2 Dickersin et al 1995 3 4
Histology Combined tumor Size Symptom (cm) No. Organ Side Year Author
Summary of clinical and histopathological features of SRST Table 1
A clinicopathological summary of all SRSTs reported in the literature is listed in Table 1. Clinically, patients with SRSTs of the ovary have abdominal pain, pelvic mass, or weight loss [1-6]. Testicular SRSTs are asymptomatic [7]. All SRSTs are unilateral and confined to the ovary or testis [1-7]. Except for 1 SRST reported in conjunction with Brenner tumor [4] and 1 SRST associated with cystic teratoma [3], all other reported SRSTs were solitary tumors. Grossly, SRSTs of the ovary are larger (mean size, 7.6 cm) than those of the testis (mean size, 0.9 cm). All SRSTs show benign behavior with excellent prognosis, and they do not recur or metastasize. Histopathologically, two distinct patterns of SRSTs are commonly observed. Some tumors are monophasic, composed of round, epithelioid cells separated by fibrous septa [1,3,4,7], and others show biphasic growth of round epithelioid cells and spindle cells [2,3,5,6]. All SRSTs have characteristic cytoplasmic vacuoles with an obvious signet-ring feature. These clear vacuoles contain no mucin or glycogen. One reported case was positive for neutral lipids in vacuolated and spindle cells by Oil red O staining [3]. Several cases revealed eosinophilic intracytoplasmic globules [1-3,6]. Immunohistochemically, all cases stained positive for vimentin [2-4,6,7]. Tumor cells also were variably positive for keratin, smooth muscle actin, or inhibin [3,4]. Immunohistochemical markers for sex-cord stromal neoplasms, such as calretinin, inhibin, CD99, and CD56, were stained in our case, but tumor cells were only immunoreactive for CD99. Ultrastructural studies for ovarian SRSTs reveal the diverse pathogenesis of the signet-ring feature. Ramzy found proteinaceous material both inside the vacuoles and in the intercellular matrix, which was moderately electrondense and flocculent with some fibrillary structures. He postulated that the signet-ring cell stromal tumor probably represents a separate tumor entity rather than a variant of the sclerosing stromal tumor [1]. Suarez et al [2] observed the intracytoplasmic eosinophilic globules and suggested these vacuoles were caused by globule elimination. Dickersin et al [3] studied 4 cases and concluded than there were 3 different
Positive IHC stains
3. Discussion
Monophasic Vimentin, keratins (AE1.3/AE3, N/A CAM5.2, wide spectrum), SMA N/A None Biphasic Vimentin, SMA N/A Weight loss Mixed with Brenner Monophasic Vimentin, SMA, inhibin A HS and BSO tumor Abdominal pain None Biphasic N/A BSO Pelvic mass None Monophasic Vimentin Oophorectomy Abdominal pain None Biphasic Vimentin HS and BSO N/A None Monophasic Vimentin Tumor excision Asymptomatic None Monophasic Vimentin, CD99 PO
16 mo 2y 17.4 y 2y HS and RSO Oophorectomy HS and BSO N/A
Treatment
Follow-up Prognosis
These vacuoles revealed neither mucin nor glycogen content on mucicarmine and periodic acid-Schiff stains. Immunohistochemically, the tumor cells reacted to vimentin (Fig. 1E) and CD99 (Fig. 1F) but were negative for AE1/ AE3, epithelial membrane antigen, estrogen receptor, progesterone receptor, calretinin, placenta-like alkaline phosphatase, inhibin-α, smooth muscle actin, desmin, S100 protein, bcl-2, CD246, CD31, CD34, CD56, and CD68. No recurrence or metastasis of this tumor was noted after 1 month follow-up.
Excellent
C. Y. Kuo et al. Excellent Excellent Excellent Excellent
586
Signet-ring stromal tumor of the testis mechanisms of signet-ring cell formation: generalized edema of cytoplasmic matrix, dilation of mitochondria in mitochondria-rich cells, and invagination of the cell membrane by the extracellular matrix. Cashell et al [4] found that many vacuoles were surrounded by a single membrane, but a few vacuoles were formed by swollen mitochondria. None of these cases showed desmosome or basement membrane formation supporting the mesenchymal origin. Based on histological, immunohistochemical, and ultrastructural study, SRSTs of the ovary are categorized in the fibroma/thecoma group of sex-cord stromal tumors by the World Health Organization [8]. We believe the SRST of the testis is identical to its ovarian counterpart and belongs to the category of sex cord stromal tumor [9,10]; however, whether it should be classified as one type of fibroma/ thecoma is still debatable. The Sertoli cell tumor often has cytoplasmic vacuoles and a nested and cord-like pattern, and the immunohistochemical studies of our case are consistent with Sertoli cell tumor. In our opinion, SRST is probably a specific variant of Sertoli cell tumor with unique histological features and distinct clinical behavior. It is important to differentiate SRST from other sex-cord stromal tumors and have a clear criterion to define SRST because other sex cord stromal tumors may have similar signet-ring cells. In one study, the proportion of signet-ring cell components in ovarian SRST ranged from 20% to 70% [6]. Irving et al [11] claimed that the term “SRST” is best reserved for tumors consisting of a significant proportion of signet-ring cells. The differential diagnosis of SRST and metastatic signetring cell carcinoma is crucial because both types of tumors have a distinct prognosis and treatment. Although rarer than metastasis to the ovary, metastatic signet-ring cell carcinomas to the testicles have been reported [12]. The welldefined growth patterns, mild cellular pleomorphism, and zero-to-low mitotic rate all indicate the benign nature of SRSTs. Unlike signet-ring cell carcinomas, SRSTs do not secrete mucin. The immunoreaction to vimentin rather than cytokeratin or epithelial membrane antigen also helps rule out metastatic carcinoma [6]. In the testis and ovary, adenomatoid tumors may consist of well-defined fibrous nodules with epithelioid tumor cells arranged in single cells, cords, and nests separated by collagen bundles. However, tumor cells of adenomatoid tumors have a glandular or tubular structure and react to mesothelial cell markers. Although very rare, epithelioid hemangioendotheliomas of the testis have been reported [13]. Histologically, epithelioid hemangioendotheliomas show solid nests and short cords of rounded or slightly spindled endothelial cells with intracytoplasmic lumens or vacuoles. This feature mimics signet-ring cells. Unlike SRSTs, intracytoplasmic lumens of epithelial hemangioendotheliomas usually contain erythrocytes, and these epithelioid endothelial cells express endothelial markers such as CD31 and CD34. In the testis, although the distinction of Leydig cell tumors and SRSTs is not critical because both tumors lack
587 malignant features, Leydig cell tumors should be included in the differential diagnosis because Leydig cell tumors with lipomatous changes consisting of vacuolated or foamy cells resemble signet-ring cells [9]. The Reinke crystals, lipid content of vacuoles, and intense immunoreactivity for inhibin of Leydig cell tumors are different from SRSTs. Luteinized thecomas histologically have luteinized cells with vacuolated cytoplasm dispersed among the spindle-shaped cells and may be confused with SRSTs. Unlike thecoma, most SRSTs are negative for inhibin immunohistochemically and contain no lipids in vacuoles. Partial orchiectomy with complete tumor excision may be adequate treatment for SRSTs. In our case, neither recurrence nor metastasis was noted after partial orchiectomy and preservation of the residual normal testis, which may be important for fertility. However, because ovarian SRSTs are clinically symptomatic and larger at presentation, they may require oophorectomy.
References [1] Ramzy I. Signet-ring stromal tumor of ovary. Histochemical, light, and electron microscopic study. Cancer 1976;38:166-72. [2] Suarez A, Palacios J, Burgos E, Gamallo C. Signet-ring stromal tumor of the ovary: a histochemical immunohistochemical and ultrastructural study. Virchows Arch A Pathol Anat Histopathol 1993; 422:333-6. [3] Dickersin GR, Young RH, Scully RE. Signet-ring stromal and related tumors of the ovary. Ultrastruct Pathol 1995;9:401-19. [4] Cashell AW, Jerome WG, Flores E. Signet ring stromal tumor of ovary occurring in conjunction with Brenner tumor. Gynecol Oncol 2000;77: 323-6. [5] Su RM, Chang KC, Chou CY. Signet-ring stromal tumor of the ovary: a case report. Int J Gynecol Cancer 2003;13:90-3. [6] Vang R, Bague S, Tavassoli FA, Prat J. Signet-ring stromal tumor of the ovary: clinicopathologic analysis and comparison with Krukenberg tumor. Int J Gynecol Pathol 2004;23:45-51. [7] Michal M, Hes O, Kazakov DV. Primary signet-ring stromal tumor of the testis. Virchows Arch 2005;447:107-10. [8] Tavassoli FA, Mooney E, Gersell DJ, et al. Sex cord-stromal tumours. In: Tavassoli FA, Devilee P, editors. World Health Organization classification of tumours: tumours of the breast and female genital organs. Lyon: IARC Press; 2003. p. 146-61. [9] Sesterhenn IA, Cheville J, Woodward PJ, et al. Sex cord / gonadal stromal tumours. In: Eble JN, et al, editor. World Health Organization classification of tumours: tumours of the urinary system and male genital organs. Lyon: IARC Press; 2004. p. 250-8. [10] Sex cord-stromal tumors. In: Ulbright TM, Amin MB, Young RH, editors. Atlas of tumor pathology. Tumors of the testis, adnexa, spermatic cord, and scrotum. Washington, D.C.: Armed Forces Institute of Pathology; 1999. p. 193-233. [11] Irving JA, McCluggage WG. Ovarian spindle cell lesions: a review with emphasis on recent developments and differential diagnosis. Adv Anat Pathol 2007;14:305-19. [12] Niesel T, Bohm J, Paul R, Breul J, Hartung R. Rare metastases of signet ring cell carcinomas to the scrotum: report of two cases. Urology 1996;47:769-71. [13] Tsolos C, Polychronidis A, Sivridis E, Kelidis G, Simopoulos C. Epithelioid hemangioendothelioma of the testis. J Urol 2001;166: 1834.