Frozen section analysis of unusual small testicular tumor masses: report of 3 cases



Nonpalpable tumors of the testis are generally incidental findings on ultrasound examination. Most of these tumors are benign but some turn out to be germinal tumors at histology. Therefore, intraoperative histopathologic analysis of nonpalpable testicular lesions is pivotal for guiding a testis-sparing surgical approach.


We report clinical and pathologic characteristics of 3 small nodules of the testis with challenging histologic features at intraoperative frozen section examination and peculiar histology. One was a known testicular mass, undertreated for 5 years, whose enlargement worried the patient, while the other 2 were incidental findings during clinical testicular examination for non-neoplastic diseases.


The 3 cases reported are characterized by small size, which limited the accuracy of preoperative ultrasound diagnosis. Intraoperative frozen section examination was able to rule out a diagnosis of germ cell malignancy in all cases, but diagnosis was conclusive only at histology. Knowledge of unexpected rare testicular lesions is of great relevance at the time of frozen section examination in view of conservative surgical strategy.

Tumori 2016; 102(Suppl. 2): e106 - e109

Article Type: CASE REPORT



Francesca Giunchi, Francesco Vasuri, Maurizio Colecchia, Giorgio Gentile, Marco Garofalo, Riccardo Schiavina, Michelangelo Fiorentino

Article History


Financial support: No financial support was received for this submission.
Conflict of interest: None of the authors has conflict of interest with this submission.

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Tumors of the testis occur in most cases as palpable symptomatic masses, which turn out to be malignant germinal cell tumors in 80%-90% of the cases. Nonpalpable tumors are generally incidental findings discovered by ultrasound (US) examination of the testicle in asymptomatic patients (1). Incidental lesions are largely benign, with only 2 (22%) malignant lesions out of 9 incidentally discovered in approximately 1,600 scrotal US done for other indications (2). While malignant germ cell tumors need radical orchiectomy as standard treatment, smaller lesions at US can be treated conservatively with testicular-sparing surgery. Nevertheless, germ cell malignant tumors can be detected in early phases as small intratesticular nodules. Therefore, intraoperative histopathologic examination using frozen section examination (FSE) is mandatory in these cases to guide surgical decision-making (1).

We report clinical and pathologic characteristics of 3 small nodules of the testis with unusual histology at FSE.

Case 1

A 36-year-old man with a previously diagnosed and untreated small painless nodule of the left testicle presented 5 years later to our outpatient urologic clinic complaining of increasing size of the nodule. At US Doppler analysis, the nodule was hypoechoic, hypervascularized, and 1 centimeter in diameter. The remaining testicular parenchyma was normal, and no inguinal lymphoadenopathies were detected. Tumor serum markers were normal.

To exclude a malignant germ cell tumor, surgical exploration was performed, the nodule excised, and intraoperative FSE requested. The macroscopic appearance of the lesion was a reddish-brown nodule 1 centimeter in size, possibly a vascular lesion, with the recommendation for conservative surgery. At FSE analysis, the lesion was composed of a proliferative and reactive vascular network within a diffuse lymphocytic infiltrate (Fig. 1A). The morphologic features at FSE suggested conservative treatment awaiting permanent histologic examination (PHE). The differential diagnoses at FSE included lymphoproliferative disease, vascular lesion, teratoma, and splenic heterotopic tissue (namely spleno-gonadal fusion).

(A-D) Case 1. Splenic tissue with white and red pulp, surrounded by a capsule and residual seminiferous tubules; frozen (A) and permanent section (B, hematoxylin & eosin [HE] stain). Immunohistochemical pattern of CD20 (C, lymphoid follicles of the white pulp) and CD3 (D, periarteriolar T-lymphocytes). Magnification 2×. (E-H) Case 2. Unclassified sex cord/gonadal stromal tumor with prevalent spindle cell component and storiform arrangement of the tumoral spindle cells, frozen (E) and permanent section (F). Tumor cells are immunoreactive for smooth muscle actin (SMA) (G) and inhibin (H). Magnification 20×. (I-L) Case 3. Carcinoid tumor of the testis on frozen (I) and permanent section (J). Immunoreactivity for the somatostatin receptor SSTR2A (K) and synaptophysin (L). Magnification 20×.

At PHE, the lesion was composed of branching arteries lined by elongated, endothelial cells with bean-shaped nuclei and nuclear clefts. These abundant blood vessels were intermingled by large amounts of red blood cells, macrophages, lymphocytes, plasm cells, and granulocytes (all components of the splenic red pulp). Lymphoid tissue with hyperplastic follicles (resembling the splenic white pulp) was admixed with the vessels. These histologic features were consistent with splenic tissue (Fig. 1B). Immunohistochemical (IHC) analysis revealed immunoreactivity of the lymphoid cells for CD3 and CD20 (Fig. 1, C and D), definitively excluding a lymphoproliferative disease, while CD31 stained the rich vascular component. Inhibin and wide-spectrum keratins were negative. On the basis of the IHC, which revealed a clear partition between the white pulp (lymphatic follicles positive for CD3 and CD20) and a red pulp (CD31-positive vascular network), a final diagnosis of spleno-gonadal fusion was made.

Seven months after surgery, the patient is alive and in good general condition. No residual disease was detectable at physical and US examination.

Case 2

A 51-year-old man with a testicular nodule discovered after a routine clinical checkup came to our urologic outpatient clinic. The physical examination confirmed the presence of a nodule in the upper left testis with no superficial lymph node enlargement. The patient was asymptomatic. At Doppler US examination, the nodule was hypoechoic and 0.8 centimeter in diameter. The remaining testicular parenchyma was normal. Tumor serum markers were normal. The nodule was excised at exploratory surgery and intraoperative FSE was requested. At gross examination, the lesion was a whitish well-circumscribed nodule of 0.7 centimeter in diameter. The lesion at FSE displayed the morphologic appearance of a spindle-cell mesenchymal proliferation, with no necrosis and with low mitotic rate (which excluded high-grade mesenchymal malignancy; Fig. 1E). The main differential diagnoses at frozen section included tumors of the fibroma-thecoma group, leiomyoma, solitary fibrous tumor, and unclassified sex cord stromal tumor. Conservative surgery was recommended awaiting PHE.

At PHE, the tumor was composed of densely packed spindle cells arranged in long fascicles with a focal storiform growth pattern, without nuclear pleomorphism, mitotic activity, or necrosis (Fig. 1F). At IHC analysis, the neoplastic cells were positive for vimentin, smooth-muscle actin (SMA, Fig. 1G), and focally for inhibin (Fig. 1H), whereas wide-spectrum keratins, S-100, MART-1, WT1, and CD117, were negative. The proliferative index (Ki67) was 5%. Based on the histologic features, the absence of necrosis, and the IHC profile, the diagnosis of unclassified sex cord/gonadal stromal tumor with prevalent spindle cell component was made. Given the general benign behavior of these neoplasms, the testis was preserved. Follow-up was carried out with US examination at 6 months and 12 months, both negative for local relapse.

Case 3

A 41-year-old man presented in December 2012 to our urology outpatient clinic complaining of low urinary tract symptoms and chronic pain to the right testis. The right testis was regular at physical examination without superficial lymph node enlargement. Doppler US revealed a hypoechoic, not hypervascularized, 5-millimeter nodule at the upper testicular pole. The remaining testicular parenchyma was normal. Tumor serum markers were normal. The patient underwent surgical exploration of the testis through inguinal access. After the excision of the nodule, FSE was requested. Grossly, the lesion was a reddish mass 0.6 centimeter in diameter. Due to the presence of nests and acini of monomorphous round cells (Fig. 1I), the intraoperative histologic diagnosis was “suspect for sex cord/gonadal stromal tumor, more likely Sertoli cell tumor,” to be confirmed on permanent sections. Hyperplastic Sertoli cell nodule and teratoma were the other 2 differential diagnoses at FSE. A conservative surgical approach was decided due to the small size of the lesion, awaiting PHE.

At PHE, the tumor architecture revealed nests and pseudoacini made of round cells, with high nuclear/cytoplasmic ratio, eosinophilic granular cytoplasms, finely granular “salt-and-pepper” chromatin, and small nucleoli. These nuclear features were not well identifiable at FSE, and raised the suspicion of a well-differentiated endocrine tumor. Some perivascular rosettes were observed as well. Necrosis, nuclear polymorphism, or atypical mitoses were absent. The suspicion of neuroendocrine tumor was confirmed by positive IHC for wide-spectrum cytokeratins, chromogranin A, synaptophysin, CD56, serotonin, and the somatostatin receptor SSTR2A (Fig. 1, J-L). Smooth-muscle actin was positive in the tumor stroma. Immunohistochemistry for inhibin, WT1, and CD117 were negative. The proliferative index (Ki67) was <5%.

A diagnosis of neuroendocrine tumor (or carcinoid tumor) localized to the testis was made. As a further comment to the diagnosis, the positivity for SMA and the absence of a primitive extragonadal endocrine localization favored a primitive germinal origin, i.e., “highly specialized monodermal teratoma,” in line with the AFIP guidelines (3).

The patient was advised to undergo radical orchiectomy for oncologic safety but he refused. An intensive follow-up was started with positron emission tomography using (68)Ga-DOTATATE that turned out negative for pathologic uptake. The patient is healthy after 6 months and was advised to undergo a long-term follow-up protocol (at least 10 years) with US examination every 6 months and a chest-abdomen computed tomography scan yearly.


We report on 3 rare lesions of the testis >1 centimeter in size. Case 1 was a known testicular mass, undertreated for 5 years, whose enlargement worried the patient. The other 2 lesions were incidental findings during clinical testicular examination for non-neoplastic diseases. Presurgical assessment of the lesions was not conclusive in any of the cases, leading to intraoperative FSE. Intraoperative histology was not conclusive due to the rarity of the lesions but led to conservative surgical strategy in all cases in the absence of true malignant features. The FSE of testicular masses is often challenging, particularly for nondedicated genitourinary pathologists, and may imply important legal implications. We demonstrate that a conservative surgical approach guided by responsible pathologic examination should be explored in challenging or rare diseases.

Splenogonadal fusion (SGF) is a rare benign malformation in which the spleen is abnormally connected to the gonad. To date, fewer than 200 cases have been reported. Most cases of SGF are seen in the first 2 decades of life, although some are not discovered until adulthood or even at autopsy (4, 5). The etiology of SGF remains unclear but it may result from the early fusion of the spleen and the gonad during embryonic development, as a result of inflammation or adhesion at the time of split. The commonest presentation is testicular swelling. Germ cell tumors associated with SGF are extremely rare and to date only 4 cases have been reported (6). These were all adult patients with undescended testis or a history of orchiopexy. No direct relationship between SGF and the development of testicular cancer have been reported (6). The presence at FSE of follicular-type inflammation mixed with vascular structures and benign cellular features should always raise the suspicion of SGF.

Incompletely differentiated sex cord/gonadal stromal tumor (SCST) is a rare neoplasm of the testis (>1% of all testicular neoplasms), composed predominantly of spindle cells and intermixed epithelioid or Leydig cells (7). It is important to differentiate these tumors from other sex-cord testicular neoplasms, particularly the other types of unclassified SCST. The IHC profile is important: in the SCST mixed type, the neoplastic cells are negative for keratins and reactive for SMA, S100 protein, and inhibin (3). Our case showed the same phenotype with the exception of S100, which was negative, while the immunoreactivity for inhibin allowed us to establish the sex-cord origin (7). Notably, our case showed a preponderance of the spindle-cell component, without a clear Leydig or Sertoli differentiation. To our knowledge, only 5 similar cases have been described so far and their histogenesis is unclear (7). There are no reports of malignant behavior of incompletely differentiated SCST. Only one reported case showed high mitotic activity, cellularity, nuclear pleomorphism, and necrosis, but the patient was healthy after 5 years (8). Nonetheless, experience with these tumors is limited and the guidelines for management and treatment of these lesions have not been defined. Therefore, the finding at FSE of a spindle cell lesion >1 centimeter without necrosis or high mitotic count should always suggest conservative treatment.

The carcinoid tumor of the testis is another rare lesion, accounting for >1% of all testicular neoplasms. These tumors are classified into 3 groups: primary testicular neoplasms (like our case), carcinoid differentiation within a mature teratoma, and metastases from an extratesticular neuroendocrine tumor (9). Only 65 cases of primary carcinoid of the testis have been described so far. Primary carcinoid of the testis does not occur in a specific age group and most of the cases do not become clinically relevant until metastatic spread or carcinoid syndrome (10% of the cases) occurs. Primary testicular neuroendocrine tumors may originate from the same progenitor cells of Leydig cells or germ cells (10). Approximately 10% of carcinoids tend to slowly metastasize even after 10 years or more (9). Radical orchiectomy is curative for testicular-confined carcinoid but long-term biochemical and radiologic follow-up is required (9). Differential diagnosis at FSE is challenging in these cases but the presence of unequivocal endocrine features or other teratomatous elements should always guide towards radical orchiectomy regardless of the size of the lesion.

The 3 cases reported are characterized by their small size, which limited the accuracy of US preoperative diagnosis. The intraoperative FSE was able to rule out a diagnosis of germ cell malignancy in all cases, but diagnosis was conclusive only at permanent histology.

The knowledge of unexpected rare testicular neoplasms is helpful in surgical decision-making in case of small testicular proliferations. When applicable, the second opinion of a dedicated genitourinary pathologist at the time of FSE should be always pursued. In doubtful cases and in the absence of truly malignant features or germ cell histologic patterns, a conservative surgical strategy should be followed.


Financial support: No financial support was received for this submission.
Conflict of interest: None of the authors has conflict of interest with this submission.
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  •  Pathology Service, Addarii Institute of Oncology, S-Orsola-Malpighi Hospital, Bologna - Italy
  •  Department of Pathology, Fondazione IRCCS Nazionale Tumori, Milan - Italy
  •  Department of Urology, University of Bologna, S-Orsola-Malpighi Hospital, Bologna - Italy

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