Incidentally detected liver metastasis of well-differentiated follicular carcinoma of the thyroid, mimicking ectopic thyroid

A case of incidentally detected liver metastasis of follicular carcinoma of the thyroid, histologically mimicking ectopic thyroid, is described. The patient was a 48-year-old woman. A 2-cm mass was incidentally detected in the left lobe of the liver by abdominal computed tomography (CT) scan. Partial liver resection was performed for diagnosis and treatment. Histologically, the liver nodule was composed of small-to-large follicles containing colloid material. The lining epithelium was flat or cuboidal and showed no cellular or nuclear atypia. Immunohistochemical studies for thyroid-specific proteins, thyroglobulin (Tg), triiodothyronine (T3) and thyroxine (T4), suggested that the nodule was of thyroid origin. Therefore, a differential diagnosis of metastasis of well-differentiated thyroid cancer, ectopic thyroid tissue and teratoma was made. The patient had a history of subtotal thyroidectomy performed 8 years ago due to a thyroid tumor. The original surgical specimens of the thyroid tumor were diagnosed as follicular adenoma. Additional sections of the specimen were reviewed and an area of convincing vascular invasion was found that was suggestive of follicular carcinoma. Subsequent whole-body examination failed to find other metastases. It was determined that the liver tumor was metastasized from well-differentiated follicular carcinoma of the thyroid.     

Supradiaphragmatic ectopic adrenocorticotropic hormone-secreting adenoma

A 22-year-old woman with Cushing's syndrome, caused by an extremely rare suprasellar ectopic pituitary adenoma, is presented. Magnetic resonance imaging and computed tomography revealed a well-circumscribed mass in the right suprasellar region. Endocrinological tests showed elevated s-adrenocorticotropic hormone level and hypercortisolemia. The tumor was totally removed by right subfrontal approach. At the time of the operation, the tumor was in continuity with the distal pituitary stalk but not with the pituitary gland. The diaphragma sellae was intact. Histologic diagnosis of the tumor specimen was confirmed as a pituitary adenoma. After surgical removal of the tumor, continued improvement in the patient's laboratory results and disappearance of her endocrine symptoms strongly indicated the absence of adenoma cells in the pituitary gland or stalk. Six years post-surgery, there was no evidence of recurrence in the patient's clinical and laboratory examination. This tumor probably originated from aberrant anterior pituitary cells of the pituitary stalk.     

The differentiation of atypical adenomas and encapsulated follicular carcinomas in the thyroid gland

Summary From 1968 to 1977 a total of 1,394 follicular neoplasms were seen in surgical material containing 4,612 thyroid glands. 1,159 tumors were obviously benign adenomas. All remaining follicular tumors with equivocal histological appearances were extensively re-examined, together with all apparently invasive follicular carcinomas. Thereby, 125 atypical adenomas, 55 encapsulated and 55 widely invasive follicular carcinomas were diagnosed. In 102 tumors a definite diagnosis was reached after excision and histological examination of ten tissue blocks from preserved wet material. In each case the number of blood vessel invasions and penetrations of tumor capsule was recorded. Among these tumors, 17/36 (47%) encapsulated carcinomas proved to be only slightly invasive. All their tissue blocks were cut into sequential sections and in 6/17 cases additional vascular invasions found. It was shown by this study that the proof of vascular invasion is more often successful than the proof of capsular penetration and therefore a better indication of malignancy in encapsulated follicular tumors. Examination of 10 tissue blocks represents the minimum effort to estimate the invasive capability of a follicular tumor, whereas sequential sections through less than 10 blocks are of little help in most cases. A follow-up study of all patients included here seems to justify the distinction we have made between atypical adenomas and encapsulated follicular carcinomas.

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Zusammenfassung In den Jahren 1968–1977 wurden insgesamt 1394 follikuläre Tumoren der Schilddrüse in einem Operationsgut von 4612 Strumen diagnostiziert. 1159 follikuläre Tumoren waren zweifelsfrei als Adenome einzuordnen. Alle übrigen follikulären Tumoren mit zunächst unklarer Dignität aber auch solche mit eindeutig invasivem Wachstum wurden histologisch eingehend nachuntersucht. Daraus resultierten 125 atypische Adenome, 55 weitgehend abgekapselte follikuläre Carcinome und 55 ausgedehnt invasive Carcinome. Bei 102 Tumoren stützte sich die endgültige Diagnose auf die histologische Nachuntersuchung von 10 Gewebsentnahmen aus dem kapselnahen Bereich. Dabei wurde die Zahl der Tumoreinbrüche in prae- oder postcapilläre Blutgefäße und die Zahl der kompletten Kapseldurchbrüche registriert. Bei 17/36 (47%) abgekapselten Carcinomen waren jeweils nur ein oder zwei Gefäßeinbrüche festzustellen. In diesen Fällen wurden die vorhandenen 10 Gewebsblöcke pro Tumor in 20 weiteren Schnittstufen aufgearbeitet und bei 6/17 zusätzliche Gefäßeinbrüche gefunden. Die quantitative Auswertung hat ergeben, daß der Nachweis von Gefäßeinbrüchen häufiger gelingt als der von Kapseldurchbrüchen und damit ein besserer Hinweis für die Malignität eines abgekapselten follikulären Tumors ist. Allerdings ist die Untersuchung von 10 Entnahmestellen das Minimum für eine zuverlässige Diagnose und mit Sicherheit nicht durch Schnittstufen mit weniger Gewebsblöcken zu erreichen. Der bisherige postoperative Verlauf aller in dieser Studie erfaßten Patienten rechtfertigt die nach den angegebenen Kriterien vorgenommene Unterscheidung zwischen atypischen Adenomen und abgekapselten follikulären Carcinomen.

     

Carcinosarcoma ex recurrent pleomorphic adenoma of the submandibular gland

We report a case of carcinosarcoma ex recurrent pleomorphic adenoma in the submandibular region of a 56-year-old Japanese man. He presented with a 2-year history of a rapidly growing mass in the submandibular region. He reported undergoing excision of a nodule in the same region 10 years earlier. Incisional biopsy confirmed the diagnosis of pleomorphic adenoma. The lesion was excised surgically. The resected tumor measured 40 x 20 mm and was composed of two large nodules and multiple small satellite nodules in the subcutaneous tissue. Histopathologically, one large nodule was carcinosarcoma while the other large nodules and small satellite nodules were pleomorphic adenoma. The former large nodule showed a variegated pattern with carcinomatous components (poorly differentiated adenocarcinoma, salivary duct carcinoma, squamous cell carcinoma and undifferentiated carcinoma) and sarcomatous components (spindle cell sarcoma, chondrosarcoma, liposarcoma and rhabdomyosarcoma). Based on the clinical history and histopathology, we consider the lesion to have originated from recurrent pleomorphic adenoma.     

Tumor-to-tumor metastasis to a thyroid follicular adenoma as the initial presentation of a colonic adenocarcinoma

The incidence of thyroid involvement by metastatic disease from distant organs ranges from an average of 3.1% in surgical series to 5.3% in autopsy series. However, the metastasis of one tumor into another (traditionally referred to as 'tumor-to-tumor metastasis') is distinctly uncommon. Typically, they are identified as new manifestations or necropsy findings of a known, pre-existing donor tumor. Herein is described the case of a 59-year-old woman whose thyroid nodule (a follicular adenoma) was resected and found to contain foci of a well-differentiated adenocarcinoma with a morphologic and immunohistochemical profile consistent with origination from the lower gastrointestinal tract. Subsequent diagnostic work-up revealed a sigmoid colon tumor with metastases to the liver. This is, to the authors' knowledge, the first reported example of a colon adenocarcinoma whose initial clinical manifestation was a metastasis to a thyroid neoplasm and only the third reported example of a colonic adenocarcinoma metastatic to a thyroid tumor. In a review of previously reported examples of tumor-to-tumor metastases involving a thyroid neoplasm as the recipient, the following features were present in the majority: (i) multifocality of the metastatic tumor aggregates; (ii) a total lack of, or only minimal amounts of reaction (desmoplastic, inflammatory or myxoid) of the recipient tumor to the metastatic deposits; and (iii) retention of the histopathologic characteristics of the donor tumor in the metastatic deposits. In general, strikingly divergent morphologic features in an otherwise typical thyroid neoplasm should elicit a differential diagnosis that takes into consideration the possibility of metastasis.     

Role of GPER1, EGFR and CXCR1 in differentiating between malignant follicular thyroid carcinoma and benign follicular thyroid adenoma

It is extremely difficult to discriminate between follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) before surgery, because the morphologies of carcinoma cells and adenoma cells obtained by fine needle aspiration biopsy (FNAB) are similar. Molecular markers may be helpful on this issue. The purpose of this study was to assess the role of GPER1, EGFR and CXCR1 in differential diagnosis between FTC and FTA. GPER1, EGFR and CXCR1 mRNA expression levels were examined in 15 FTCs and 10 FTAs using real-time RT-PCR. FTC showed to have significantly increased mRNA levels of the three molecules compared to FTA (P < 0.001 for all the three molecules). GPER1, EGFR and CXCR1 protein expression in 106 FTCs and 128 FTAs were analyzed using immunohistochemistry. The rates of GPER1, EGFR and CXCR1 high expression were 73.6%, 72.6% and 70.8% in FTC and 30.5%, 28.1% and 27.3% in FTA, respectively. Statistical analysis showed that GPER1, EGFR and CXCR1 protein expression were correlated with one another in FTC and concomitant high expression of the three molecules had stronger correlation with the occurrence of FTC than did each alone. The positive predictive values (PPV) for concomitant high expression of the three molecules for discriminating between FTC and FTA were 91.0% for GPER1/EGFR, 93.8% for GPER1/CXCR1, 92.3% for EGFR/CXCR1 and 98.2% for GPER1/EGFR/CXCR1, respectively. These results indicated that the evaluation of GPER1, EGFR and CXCR1 concomitant high expression may be helpful in differential diagnosis between FTC and FTA.     

Minimally invasive follicular thyroid carcinoma

Infiltration of the capsule, vascular invasion, and/or neoplastic extension into the adjacent parenchyma are regarded as prerequisites for the diagnosis of follicular carcinoma. In modern practice, most of these tumors fall into the category of follicular carcinoma, minimally invasive (FCMI) characterized by evidence of limited capsular or vascular invasion with an excellent long-term prognosis and a good patient outcome. Notwithstanding the wide acceptance of the diagnostic criteria established by the World Health Organization for the classification of follicular carcinomas in particular, they have been difficult to apply and have led to a great deal of confusion. This confusion is compounded when applied to "low-grade" or "minimally invasive" follicular carcinoma because of the poor reproducibility of the classification and the variable results reported in the literature. Our surgical colleagues face a similar lack of a standardized treatment for low-grade follicular carcinomas, which leads to unnecessary surgical treatment. Standardization of histologic criteria is necessary to promote confidence and uniformity in the therapeutic approach of these tumors. We believe that a FCMI is defined as an encapsulated follicular tumor (not papillary), with only small to medium vessel invasion within or immediately adjacent to the tumor capsule and/or up to full-thickness capsular transgression without accompanying extension into the thyroid parenchyma with intervening fibrosis. By using these criteria, patients can be managed with conservative surgical excision to yield an excellent long-term patient outcome.     

Cytopathology of follicular lesions of the thyroid gland

Fine needle biopsy is generally considered unreliable in the differential diagnosis of follicular lesions of the thyroid gland. To test this hypothesis, we correlated fine needle biopsy diagnoses with surgical diagnoses in 379 follicular lesions. From nuclear characteristics (especially size) and the architectural pattern of tissue fragments, the following observations were made. Differentiation of goiters (including hyperplastic ones) from neoplastic thyroid disease is quite accurate and no more than 1 to 2% of cancers should be missed. The specific cytologic diagnosis of follicular carcinoma is 75% accurate, and that of follicular variant of papillary carcinoma is over 95% accurate. Of histologically proved follicular carcinomas, almost three-quarters should be diagnosed as such or strongly suspected by fine needle biopsy. The remainder will be identified as cellular follicular adenomas, reaffirming the overlap of cytologic features of benign and malignant neoplastic disease. From cytologic and surgical pathologic data for each fine needle biopsy diagnosis of follicular lesion, a probability of cancer can be stated that is useful in management decisions.     

Immunohistochemical demonstration of lactoferrin in follicular adenomas and thyroid carcinomas

Summary By immunohistochemistry, the presence of lactoferrin was investigated in follicular adenomas (10 cases) and carcinomas of the thyroid gland (23 cases). Normal thyroid tissue was also tested as control.Follicular adenomas showed a consistant negativity, whereas follicular and papillary carcinomas exhibited various degrees of positivity for lactoferrin. Incorporated organoid structures observed in anaplastic carcinomas were strongly stained; the spindle cell parts of these cancers were always negative for this iron-binding protein. Medullary carcinomas were also unstained.These findings are discussed in relation to the distribution pattern of thyroglobulin.The authors emphasize the possibility that lactoferrin may be useful in clarifying some diagnostic problems in neoplastic thyroid pathology.     

Computerized nuclear morphometry in thyroid follicular neoplasms

Differential diagnosis of follicular adenoma (FA) and follicular carcinoma (FC) of the thyroid can be challenging in the routine practice of surgical pathology because the diagnosis of FC is strictly defined and identification depends on the presence of invasion of the capsule or blood vessels. These features may be equivocally presented in the histological sections and interpreted subjectively by different pathologists, so an objective approach to solve this problem is essential. Computerized morphometry is a scientific tool to evaluate cellular changes and it can enhance the interpretation of morphological features by the transformation of pathological changes in cells to a qualitative form. The present study investigated the diagnostic role of objective computerized nuclear morphometry in follicular neoplasms. Thirty-six cases of thyroid FC and 36 cases of FA from patients who were matched by age and sex were studied. Four nuclear parameters were selected and analyzed: mean nuclear area, mean nuclear perimeter, largest to smallest diameter ratio of the nuclei, and coefficient of variation of the nuclear area. The results indicate that all the chosen nuclear variables were significantly correlated with the FA and FC studied. In conclusion, computerized nuclear morphometry can be considered a helpful ancillary tool for differential diagnosis of FA and FC.     

Examination of CD26/DPPIV,p53, and PTEN expression in thyroid follicular adenoma

Tumor cytology has proven to be inadequate for precise diagnosis of thyroid follicular adenoma. This suggests the need for a molecular approach for its diagnosis. Expression of CD26/DPPIV (dipeptidyl peptidas IV), p53, and PTEN was analyzed in smears or sections obtained from 19 patients with histologically proven thyroid follicular adenoma. Papanicolaou staining, CD26/DPPIV activity staining, and HE staining were performed and the specimens were observed morphologically. Immunohistochemical analysis using antibodies against p53 and PTEN was performed. Genetic mutation of PTEN exons was performed using the laser capture microdissection method. The nuclear area of the CD26/DPPIV‐positive cells was significantly larger than that of the CD26/DPPIV‐negative cells. p53 expression was not observed any specimen. PTEN expression was observed in 18 of 19 cases. DNA sequence analysis did not reveal mutations in exons 5–9 of PTEN in the immunohistochemically PTEN‐negative case. In accordance with our previous reports, we found that observation of concomitant CD26‐positive and PTEN‐negative status in cases of follicular adenoma suggests a state close to follicular carcinoma or progression to cancer, thus warranting careful follow‐up. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.     

Phenotypic expression of human epidermal growth factor in foetal submandibular gland and pleomorphic adenoma of salivary gland

Summary The phenotypic expression of the human epidermal growth factor (EGF) was investigated immunohistochemically in human foetal submandibular glands from the 5th to 10th month of gestation, adult normal submandibular glands and 48 cases of pleomorphic adenomas. In foetal submandibular glands, both the terminal buds and primary ducts at the intermediate stage of gestation were positive for EGF, and in particular, the outer layer cells of primary ducts showed strong EGF-immunoreactivity. EGF-positive cells decreased as the gestational stage advanced and only ductal cells were weakly positive for EGF at the terminal stage of gestation. In the adult normal submandibular gland, weak immunoreactivity for EGF was restricted to ductal cells. However, 41 (86%) of the 48 pleomorphic adenomas had EGF-positive cells which were distributed among the ductal, chondroid and myxoid portion. No EGF-immunoreactivity was detected in the solid portion of pleomorphic adenomas. These results suggest that EGF may play an important role in the growth and differentiation of foetal cells as well as the proliferation of tumour cells in pleomorphic adenomas.