Arne Heilo

Gonadal Function and Fertility in Patients with Bilateral Testicular Germ Cell Malignancy

OBJECTIVE To evaluate gonadal function and fertility in patients with bilateral testicular cancer (TC). METHODS In 1999, 63 patients with bilateral invasive TC or carcinoma in situ (CIS) in the contralateral testis completed a mailed questionnaire evaluating their fatherhood (Cases). Their gonadal function had also been assessed after the first orchiectomy for TC before further treatment. The results were compared with those from 174 patients with unilateral TC (Controls). RESULTS In Cases the post-orchiectomy serum levels of FSH and LH were above those of the Controls (p<0.001). Serum testosterone was similar, whereas sperm concentrations were lower in Cases (p<0.001). In Cases with metachronous invasive TC the level of serum FSH was associated with the interval between the two diagnoses. After the first orchiectomy, 10 of 25 Cases (40%) initiated a pregnancy, in 4 Cases by assisted fertilization. In the Control group 74% of the patients who attempted fatherhood succeeded (p=0.002). CONCLUSIONS After unilateral orchiectomy for TC elevated serum FSH and/or oligospermia represent a high-risk factor of metachronous bilateral TC or synchronous CIS. At least one-third of these patients attempting fatherhood are successful after the first orchiectomy. Assisted fertilization is often necessary and the overall paternity rate is below that of patients with unilateral TC.

Regional Lymph Node Metastases

Regional lymph node metastases are a common finding in papillary and medullary carcinomas, but they are very rare in follicular carcinoma because this tumor usually spreads hematogenically. Lymph node affection is often seen in thyroid lymphomas, and reactive lymph nodes are found in thyroiditis. Reactive lymph nodes are usually enlarged, but metastatic infiltration does not necessarily cause enlargement. Thus, lymph node size is not a reliable criterion in the differential diagnosis [6,23].

Follicular Variant of Papillary Thyroid Carcinoma

Morphologically,follicular variant of papillary thyroid carcinoma (FVPTC) may appear partially or completely encapsulated and can be misdiagnosed as follicular adenoma or follicular carcinoma pathologically and on (ultrasound) examination. They can be hyper-, iso-, hypoechoic, or mixed with an uneven hypoechoic capsule that is hypervascular with a “spoke-and-wheellike” appearance. Some have sharply marginated areas of different echogenicity within the tumor, a feature we introduce as geographic echo pattern (see page 9). If microcalcifications are found inside the tumor, FVPTC is more likely the diagnosis.These encapsulated FVPTC are often solitary. If they are not encapsulated, they often look like an ordinary PTC both pathologically and on US examination [17].

Nodular or Colloid Goiter, Hyperplasia, and Cysts

These thyroid nodules are often described as hyperplastic, adenomatous, or colloid. Most cystic thyroid lesions are hyperplastic nodules that have undergone extensive liquefactive degeneration. The common features of a nodular goiter are multinodular inhomogeneous, well-circumscribed solid, semi-solid or mostly cystic tumors. Some are hyperechoic compared with the echogenicity of the normal thyroid tissue, some are isoechoic, and still others hypoechoic. The hyper- and isoechoic nodules are often partially circumscribed by a thin hypoechoic halo. The nodules may contain coarse calcifications within the tumor, or peripheral “eggshell” calcifications. The cystic areas are often purely anechoic, but they may also be hypoechoic or show fluid-fluid levels due to intracystic bleeding, often with avascular internal debris. Many, even tiny cysts, contain small, strongly hyperechoic foci, often with “comet tail” artifacts. These foci represent crystallized colloid. Some cysts have intracystic avascular septae and/or papillary solid tissue protruding from the wall. Some cystic nodules have a spongy or honeycomb-like appearance. The vascularity varies a lot when evaluated on color Doppler imaging. Sometimes only spreading, faint vascularity is observed throughout the nodule, but often there is strong vascularity inside the nodule combined with a distinct peripheral border flow.

Ultrasound Features of Thyroid Lesions

There are many different features indicating a certain benign or malignant tumor type, but many of these are overlapping signs. Combining several features is considered to give the best result. Ultrasound features of benign lesions are often described as a diffusely enlarged gland, a well-circumscribed inhomogeneous hyper- or isoechoic solid lesion, a semi-solid or predominantly cystic lesion, multinodular lesions, and so forth. US features suggestive of malignant thyroid tumors have been described as follows: microcalcifications, hypoechogenicity, a taller than wide lesion, predominantly solid composition, irregular borders, absence of peripheral halo, intranodular hypervascularity, and regional lymphadenopathy [4,8,9]. No US feature has both a high sensitivity and a high positive predictive value for thyroid carcinoma. The different malignant tumors have to some degree a different appearance on US.

Physical and Technical Essentials

There are confusing, and to a certain degree misleading, discrepancies between different countries, different medical centers, anddifferent specialties in the terminology concerning the sampling of specimens for cytology and histology. In the United States, samplingof specimens for cytology and histology are called biopsy: fine needle aspiration biopsy (FNAB or FNA biopsy), which gives a specimen for cytology, and coarse or core needle biopsy (CNB), which gives a specimen for histology. In Europe, most often anotherterminology is used: fine needle aspiration cytology (FNAC or FNAC cytology), cutting biopsy (CB), core needle biopsy (CNB),or just biopsy. Large needle biopsy (LNB) is also used by some authors. Some regard an 18-gauge needle as a fine needle.

Papillary Thyroid Carcinoma

Papillary thyroid carcinomas (PTCs) are solid, usually hypoechoic tumors with inhomogeneous echo structure. They usually have irregular margins and often contain discrete echogenic foci, ie, microcalcifications. They may be solitary or multifocal. In our experience the vascularity varies from avascular to strongly vascularized. In our opinion, the ultrasound findings with highest accuracy for PTC show low echogenicity, microcalcifications, irregular margins, and neck lymph node metastases [4,6–10]. Uncommon features include hyperechoic or mixed echo texture, cysts, hypovascularity, and coarse or peripheral calcifications [18].

Medullary Thyroid Carcinoma

Medullary thyroid carcinoma (MTC) is typically located at the junction of the upper third and the lower two thirds of the thyroid lobes [6]. MTC consists of sheets of spindle-shaped, round or polygonal C cells separated by fibrous stroma [19]. The tumors are usually solitary, strongly hypoechoic, and sharply circumscribed with a homogeneous echo pattern, except for centrally located calcifications that may be of the micro type. They may, however, be more coarse than the calcifications found in papillary carcinomas [6,10]. The same type of calcifications are often found in regional lymph node metastases [(6,7].

Oncocytic Nodule/Hürtle Cell Tumors

Formerly oncocytic lesions were regarded as a definite entity, but this classification is no longer used. Cytopathologists define oncocytic cells as follows: “Oncocytic follicular cells in the thyroid, known as Hurtle cells, are characterized by large size, polygonal to square shape, distinct cell borders, voluminous granular and eosinophilic cytoplasm, and a large, often hyperchromatic nucleus with prominent cherry pink macronucleoli”. The proliferation of oncocytes gives rise to hyperplastic and neoplastic nodules. Oncocytic cells may behave as follicular carcinomas including capsular and vascular invasion, or they may behave as papillary carcinomas showing papillary architecture.

Lymphoma and Plasmacytoma

A lymphoma may affect the whole gland, but is often found only on one side. The regional lymph nodes are often affected as well. In about 70% of cases lymphoma arises from a preexisting chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis) [6,7,20]. The tumor is strongly hypoechoic, often well marginated, but usually causes enlargement of the affected lobe. The echo pattern varies from micronodular to homogeneous. Thyroid lymphomas are usually poorly vascularized, but may also show blood vessels with chaotic distribution [6]. The micronodular lymphomas may resemble Hashimoto’s thyroiditis, and may also be surrounded by thyroiditis.