Pilar González-Peramato

Sertoli cell dedifferentiation in human cryptorchidism and gender reassignment shows similarities between fetal environmental and adult medical treatment estrogen and antiandrogen exposure.

Studies over the last years show an increase in testicular cancer, hypospadias and cryptorchidism in industrial countries, leading to the concept of testicular dysgenesis syndrome (TDS). It is hypothesized that TDS is caused by estrogen and antiandrogen exposure during fetal life, accompanied by incomplete maturation of testicular Sertoli cells (SC). However, it is not known if SC disruption is a primary cause or a response to fetal Leydig cell testosterone production changes. To determine if SC differentiation is directly affected by estrogens, we compared SC maturation between adult gender reassignment cases exposed to estrogen and antiandrogen therapy, and those of typical TDS in adult cryptorchidism. We found similar expression of immature SC markers M2A antigen, inhibin bodies and Anti Mullerian Hormone, and the absence of maturation marker androgen receptor in SC of both types of patients. These data supports the occurrence of true SC dedifferentiation caused by estrogen exposure in adult humans. Our data also suggests that SC maturation is directly disrupted in TDS.

Fine Needle Aspiration Cytology of Solid Papillary Carcinoma of the Breast

BACKGROUND: Solid papillary carcinoma of the breast (SPCB) is a distinctive form of papillary carcinoma that tends to occur in older women and usually has a favorable prognosis. CASES: We report the cytologic and histologic findings in four cases of SPCB. All but one of the patients were elderly women (mean age, 66 years). Three patients presented with breast masses, and one patient presented with a breast mass and nipple discharge. Cytology demonstrated moderately to highly cellular smears with irregular groups of predominantly monolayered epithelium composed of small, polygonal or cuboidal cells with eosinophilic cytoplasm and rounded, eccentrically placed nuclei. Papillalike clusters with thin, fibrovascular cores were also observed. Immunocytochemical expression of synaptophysin was present in two cases. The diagnosis of SPBC was subsequently confirmed histologically and immunohistochemically. CONCLUSION: The FNA of SPCB displays some features that may be helpful in its correct identification preoperatively.

Primary intratesticular spindle cell tumors: interdigitating dendritic cell tumor and inflammatory myofibroblastic tumor.

Spindle cell neoplasms arising in the testis are uncommon; most cases belong to the category of gonadal stromal tumors, and the presence of distinctive clinical and pathological features usually lead to a definitive diagnosis. In some instances, however, the diagnosis of these tumors can be challenging and special techniques are needed. The present study reports 2 unusual cases of primary intratesticular tumors showing a striking morphology, characterized by spindle to stellate cells in a lymphoid background. The diagnosis of interdigitating dendritic cell tumor and inflammatory myofibroblastic tumor was established in the 2 cases, and their probable origin in cells of the accessory immune system is discussed. Although both tumors share similar histological features, their immunohistochemical profiles were decisive for a definitive diagnosis.

Surgical Treatment of Varicocele

Varicocele has a high prevalence in males, being diagnosed in 35 % of men who present with primary infertility. Surgical correction of varicocele is a therapeutic option to solve infertility in some couples seeking offspring. Indications for surgical correction of varicocele depend on whether patients are adults or adolescents. In adults, surgical treatment is indicated in patients with scrotal pain, palpable varicocele, abnormal semen analysis, or wanting to have offspring. In adolescents, surgical treatment should be considered in patients with decreased testicular size and significant alterations in semen parameters.

Rete Testis Dysgenesis as a Marker of Undescended Testis

Undescended testes in adults often show changes that may affect all its structures in varying degrees. The tunica albuginea is thin and poorly collagenized. The wall of the seminiferous tubules shows an abnormal constitution. The maturation of the seminiferous epithelium may be incomplete, and there are even seminiferous tubules without germ cells. Leydig cells have a tendency to distribute irregularly and form large clusters. The rete testis is not an exception, and its development can be altered, sometimes keeping its prepubertal appearance, others showing abnormal development. In the first case, the flattened cavities characteristic of mediastinal rete testis are not formed; in the second case a proliferation of small glands or papillae occurs which are lined by cuboidal or columnar epithelium rather than the flat squamous epithelium of normal rete. In these cases a differential diagnosis with both primary malignant lesions such as adenocarcinoma of the rete testis and secondary lesions such as metastatic adenocarcinoma from other locations should be established.

Metaplasias of the Testicular Tunica Vaginalis

The vaginal cavity is lined with a layer of mesothelial cells. It contains a small amount of fluid that allows the testis to move. This liquid is the product of a balance between production in the visceral tunic and reabsorption by the lymphatic vessels of the parietal tunic. Testis or epididymis infections, varicocele, trauma, and tumors favor the formation of a hydrocele, with the consequent change in the chemical composition of the fluid from the vaginal cavity. Chronic irritations are one of the most common causes of metaplastic processes. Different types of metaplasias are described in the tunica vaginalis: urothelial metaplasia, Mullerian metaplasia, mucinous metaplasia, squamous metaplasia, and gastric metaplasia. Urothelial metaplasia is the most frequent type and has been linked to Brenner paratesticular tumors. The Mullerian metaplasia can occur with a thickening of the tunica vaginalis, suggesting a tumor consisting of multiple cystic formations (cystic florid mullerianosis) whose epithelium is similar to the endosalpingiosis of the uterine tube. It is not known whether it is the precursor lesion of serous ovarian-like tumors described in paratesticular structures. The remaining forms of metaplasia are rare.

Reactive Mesothelial Hyperplasia Versus Mesothelioma

The tunica vaginalis, in response to certain stimuli, reacts the same as the pleura, pericardium, or peritoneum do. The reaction to injury determines that the mesothelial proliferation may exceed the normal regeneration resulting in a reactive mesothelial hyperplasia. The reactive mesothelial hyperplasia can be so florid that it may histologically mimic, even for an experienced pathologist, some malignant tumors such as mesothelioma or metastasis of an adenocarcinoma. The data provided by immunohistochemistry in the differential diagnosis with mesothelioma show that any antibody has a discriminatory specific value. More valuable is the demonstration of homozygous deletion of the 9p21 locus that is present, using FISH, in between 67 and 83 % of mesotheliomas and is not observed in reactive mesothelial hyperplasia. Electron microscopy does not provide useful data. Attention is drawn to the great diagnostic value of certain histological characteristics of the malignant mesothelioma, such as the presence of tubular, glandular, and papillary formations back to back in a little stroma, and how they infiltrate the underlying structures, the cytologic features of cells, and the presence of necrosis and invasion of vessels.

Testicular Changes in Elderly Men

The testes of the elderly show two types of lesions, some of them are directly related to aging, and the second type are lesions secondary to an associated pathology (endocrine, toxic, vascular, and obstruction of the spermatic pathway). Lesions directly related to aging are diffuse and affect all the testicular structures. Shortening and wall thickening of the seminiferous tubules occurs. Sertoli cells decrease in number and accumulate abundant lipids. The number of Ap and B spermatogonia decreases, and hypertrophic and multinucleated spermatogonia increase. The number of spermatocytes becomes reduced and megalospermatocytes increase. Multinucleated and misshapen spermatids are more abundant. Leydig cells decrease, and multinucleated cells appear in the interstitium of both Leydig cells and CD34-positive fibroblasts. These diffuse lesions are added with associated focal lesions secondary to obstructive processes localized in the epididymis (efferent ductule atrophy of an ischemic mechanism, inflammatory, or due to hormone deprivation) or in the testis itself through compression of the rete testis by dilated varicose veins.

Meaning of the Finding of Testicular and Paratesticular Calcifications

The systematic practice of ultrasounds in patients with testicular pathology has revealed, in many cases, the presence of both intratesticular and extratesticular calcifications. The combination of clinical data and ultrasound images with histological studies has allowed to know not only the characteristics of those calcifications but, what is more important, their relationship to different diseases. In this chapter ultrasound image has been taken as a starting point as it explores more tissue than histology. Calcifications are classified in testicular and paratesticular. Testicular calcifications are grouped into three sections: testicular microlithiasis, non-microlithiasis testicular calcification (macrocalcification), and tumor-associated calcification. The testicular microlithiasis is defined by the presence of concentric laminated calcifications up to 1 mm diameter (microliths) in the testicular parenchyma. Two types, classic (more than five microliths by ultrasound field) and limited (five or less microliths per ultrasound field) are distinguished. The macrocalcification is defined as any focus of “coarse” calcification that is larger than 1 mm and separated from any intratesticular mass, if any one is present. Paratesticular calcifications can be localized in the epididymis, testis and epididymis appendix, and tunica vaginalis or inside the intravaginal space. In each type of calcification, the most frequent pathology associated with it is studied.

Intratesticular and Paratesticular Patterns of Mesonephric Remnants

The study of surgical specimens of testes, epididymis, spermatic cords, and hernial sacs frequently permits to observe groups of glandular or tubular formations. Most often these formations resemble efferent ductules or the main duct or epididymis either by the characteristics of their epithelium or by the presence of a layer of surrounding smooth muscle. The correct interpretation of these structures prevents confusing them with normal structures of the spermatic pathways such as efferent ductules, epididymis or vas deferens, or, what is more serious, with a primary tumor or a metastasis. Immunohistochemical studies show a strongly positive expression for estrogen, androgen, and progesterone. Particularly interesting is the expression of CD10 in the apical edge that allows to consider them mesonephric remnants with varying degrees of differentiation. Special attention is devoted in this chapter to florid hyperplasia of intratesticular mesonephric remnants both for its rarity and for the differential diagnosis it can present with testicular tumors.