A clinicopathologic study of minimally invasive follicular carcinoma of the thyroid gland with a review of the English literature.

BACKGROUND: The criteria for minimally invasive (low grade) follicular carcinoma of the thyroid (MI) remain controversial, often resulting in unnecessary treatment. METHODS: The records of 130 patients with minimally invasive (MI) follicular thyroid carcinoma were retrieved from the files of the Endocrine Tumor Registry of the Armed Forces Institute of Pathology. RESULTS: Ninety-five patients were confirmed to have MI based on the authors' criteria of small-to-medium vessel invasion, capsular invasion of up to full thickness, no parenchymal tumor extension, and no tumor necrosis (patients with oxyphilic tumors were excluded). The remaining 35 patients had tumors that were reclassified as "not low grade" based on large vessel invasion, extension into parenchyma, and tumor necrosis (oxyphilic cases excluded). The MI patients included 67 women and 28 men, ages 20-95 years (average, 42.0 years). Nearly all patients presented with a thyroid mass (n = 90 patients). The mean tumor size was 2.8 cm. Histologic features examined for tumor classification included cellularity, capsule nature, capsular invasion, vascular invasion, extension into parenchyma, cytoplasmic oxyphilia, mitotic activity, and necrosis. All patients were treated with surgical excision. Adjuvant radioactive iodine therapy was performed in 24 patients. Five patients developed recurrent disease: four were alive or had died without evidence of disease after additional treatment (mean, 18.1 years), and one patient died with disease (MI tumor) at 15.1 years. All of the remaining patients were disease free (mean follow-up, 16.5 years). CONCLUSIONS: There are reproducible histologic criteria to diagnose patients with MI follicular carcinoma. The overall excellent long term prognosis and a good patient outcome suggests that no additional surgery is necessary.

Telecytologic diagnosis of breast fine needle aspiration biopsies. Intraobserver concordance.

OBJECTIVE: To determine the intraobserver concordance between telecytologic and glass slide diagnosis of breast fine needle aspirates. STUDY DESIGN: Twenty-five cases, originally received in consultation, were each examined by three cytopathologists. An average of seven compressed digital images per case were presented, together with a brief clinical history, using the http protocol and an internet browser. RESULTS: Agreement between the telecytologic and glass slide diagnosis ranged from 80% to 96%. Nevertheless, two cases that had been unequivocally diagnosed as malignant based upon video images were considered to be benign by the same pathologist when reviewing the glass slides. Both diagnostic confidence and self-concordance were higher for one pathologist having significant previous video microscopy experience. CONCLUSION: Although intraobserver concordance between telecytologic and glass slide diagnoses of breast fine needle aspirates is high, refinement of existing criteria for diagnosis of malignancy, taking account of the particular limitations associated with telecytologic diagnosis, may be prudent prior to widespread use of telecytology for fine needle aspiration evaluation.

From the archives of the AFIP. Paragangliomas of the head and neck: radiologic-pathologic correlation. Armed Forces Institute of Pathology.

Paragangliomas of the head and neck are ubiquitous in their distribution, originating from the paraganglia or glomus cells within the carotid body, vagal nerve, middle ear, jugular foramen, and numerous other locations. The typical patient is middle-aged and presents late in the course of the disease, with a painless slow-growing mass. Clinical manifestations include hoarseness of voice, lower cranial nerve palsies, pulsatile tinnitus, and other neuro-otologic symptoms. The overall prognosis of patients with a cervical paraganglioma is favorable, whereas its temporal bone counterpart often results in recurrence, residual tumor, and neurovascular compromise when in the advanced stage. Pathologic examination reveals a characteristic biphenotypic cell line, composed of chief cells and sustentacular cells with a peripheral fibrovascular stromal layer that are organized into a whorled pattern ("zellballen"). Imaging hallmarks of paragangliomas of the head and neck include an enhancing soft-tissue mass in the carotid space, jugular foramen, or tympanic cavity at computed tomography; a salt-and-pepper appearance at standard spin-echo magnetic resonance imaging; and an intense blush at angiography. Imaging studies depict the location and extent of tumor involvement, help determine the surgical approach, and help predict operative morbidity and mortality. Surgical treatment is definitive. Radiation treatment is included as a palliative adjunct for the exceptional paraganglioma not amenable to surgery.

Clarity on the diagnosis line (the devil is in the details)

The diagnosis line of a surgical pathology report obviously influences therapy and is often critical for proper initiation of same. If the word choice, phrasing, or terminology in the diagnosis is potentially ambiguous or subject to misinterpretation, this could have adverse or sometimes even disastrous consequences. Usually the potential for misinterpretation is a subtle facet of the wording and is not apparent to the pathologist. This discussion aims to help the pathologist become more aware of the types of subtle wording nuances that can be important and we hope to foster the habit of searching for and correcting such potentially troublesome nuances.

Large degenerated adrenal adenomas: radiologic-pathologic correlation.

PURPOSE: To correlate the radiologic and pathologic findings and differential diagnosis of large, degenerated adrenal adenomas. MATERIALS AND METHODS: The authors reviewed the radiologic and pathologic characteristics of 30 large adenomas with cystic regions or areas of heterogeneity that were either intrinsic or demonstrated at contrast material-enhanced computed tomography (CT) or magnetic resonance (MR) imaging. Images of 24 adrenocortical carcinomas were also reviewed to determine whether differentiating characteristics existed. RESULTS: Most of the adrenocortical adenomas were in asymptomatic women. Ten adenomas contained calcification. Pathologic examination revealed good correlation between heterogeneity and liquefied regions. Histologic examination confirmed regions of adenomatous tissue with areas of hemorrhage, amorphous degenerated material, calcification, and fibrosis. Some tumors contained myelolipomatous foci. Although some clinical and imaging findings differed between the groups, no features could be found that enabled the radiologic differentiation of adenomas from carcinomas. CONCLUSION: A subgroup of adrenal adenomas are larger, more heterogeneous, and more frequently calcified than those with the usual imaging findings. Central necrosis, hemorrhage, or both are responsible for many of the imaging features. Differentiation of these lesions from other large adrenal masses, including adrenal carcinoma, cannot be made by means of imaging alone; resection is required for the definitive diagnosis.

Congenital cystic masses of the neck: radiologic-pathologic correlation.

Cervical congenital cystic masses constitute an uncommon group of lesions usually diagnosed in infancy and childhood. The most common congenital neck mass is the thyroglossal duct cyst. The diagnosis is easily established from the presence of a cystic lesion in the anterior midline portion of the neck. The vast majority of branchial cleft cysts arise from the second branchial cleft. They can occur anywhere from the oropharyngeal tonsillar fossa to the supraclavicular region of the neck. Cystic hygroma is the most common form of lymphangioma. In the neck, cystic hygromas are most commonly found in the posterior cervical space. They typically extend into adjacent structures without respecting the fascial planes. Dermoid and epidermoid cysts result from sequestration of ectodermal tissue. The floor of the mouth is the most common location in the neck. Cervical thymic cysts are very uncommon lesions and are found anywhere from the angle of the mandible down to the sternum. Laryngoceles are classified into internal, external, and mixed types and have a frequent association with laryngeal carcinoma.

Mucinous cystic neoplasm (mucinous cystadenocarcinoma of low-grade malignant potential) of the pancreas: a clinicopathologic study of 130 cases.

Mucinous cystic neoplasms (MCNs) of the pancreas are uncommon tumors. The classification and biologic potential of these neoplasms remain the subject of controversy. Attempts to classify these tumors in a similar manner to ovarian MCNs remains controversial, as even histologically benign-appearing pancreatic MCNs metastasize and are lethal. One hundred thirty cases of MCNs were identified in the files of the Endocrine Pathology Tumor Registry of the Armed Forces Institute of Pathology from the years 1979 to 1993. The pathologic features, including hematoxylin and eosin staining, histochemistry, immunohistochemistry (IHC), cell cycle analysis, and K-ras oncogene determination were reviewed. These findings were correlated with the clinical follow-up obtained in all cases. There were 130 women, aged 20-95 years (mean age at the outset, 44.6 years). The patients had vague abdominal pain, fullness, or abdominal masses. More than 95% of the tumors were in the pancreatic tail or body and were predominantly multilocular. The tumors ranged in size from 1.5 to 36 cm in greatest dimension, with the average tumor measuring >10 cm. A spectrum of histomorphologic changes were present within the same case and from case to case. A single layer of bland-appearing, sialomucin-producing columnar epithelium lining the cyst wall would abruptly change to a complex papillary architecture, with and without cytologic atypia, and with and without stromal invasion. Ovarian-type stroma was a characteristic and requisite feature. Focal sclerotic hyalinization of the stroma was noted. This ovarian-type stroma reacted with vimentin, smooth muscle actin, progesterone, or estrogen receptors by IHC analysis. There was no specific or unique epithelial IHC. K-ras mutations by sequence analysis were wild type in all 52 cases tested. Ninety percent of patients were alive or had died without evidence of disease (average follow-up 9.5 years), irrespective of histologic appearance; 3.8% were alive with recurrent disease (average 10 years after diagnosis); and 6.2% died of disseminated disease (average 2.5 years from diagnosis). Irrespective of the histologic appearance of the epithelial component, with or without stromal invasion, pancreatic MCNs should all be considered as mucinous cystadenocarcinomas of low-grade malignant potential. Pancreatic MCNs cannot be reliably or reproducibly separated into benign, borderline, or malignant categories.

Thyroid papillary carcinoma of columnar cell type: a clinicopathologic study of 16 cases.

BACKGROUND: Thyroid papillary carcinoma of columnar cell type is considered an uncommon histologic subtype of papillary carcinoma characterized by its morphologic features and purportedly aggressive biologic course. METHODS: Sixteen cases of thyroid papillary carcinoma of columnar cell type were identified from the Endocrine Tumor Registry at the Armed Forces Institute of Pathology and the Washington Hospital Center. Clinical records and follow-up were available in all cases. Paraffin blocks were available for histochemical and immunohistochemical studies in 15 of the 16 cases. RESULTS: Of the 16 cases reported, 13 patients were female and 3 were male. The ages ranged from 16-76 years (average, 47 years; median, 40 years). An asymptomatic neck mass was the most common clinical presenting symptom. Macroscopically, the tumors varied from circumscribed or encapsulated to infiltrative, ranging in size from 1.5-6.5 cm. Histologically, the tumors had diverse growth patterns, including papillary, solid, microfollicular, and cribriform. A common pattern was the presence of markedly elongated follicles arranged in parallel cords. Colloid-filled follicles could be found, at least focally, in all cases. The characteristic histologic appearance included the presence of elongated cells showing nuclear stratification. Other features included the presence of vacuolated-appearing cells, spindle-shaped cells, and squamoid nests. Limited areas in the tumors showed morphologic features typical of thyroid papillary carcinoma. In 14 of the cases, the tumor was encapsulated, showed limited invasive growth, or was a microscopic tumor. In two of the cases, there was extrathyroidal invasion. Immunohistochemical studies showed consistent reactivity with cytokeratin and vimentin; varied reactivity with thyroglobulin, epithelial membrane antigen, carcinoembryonic antigen, and LeuM1; and no reactivity with calcitonin or chromogranin. Treatment was by surgical resection; supplemental radioactive iodine therapy was administered in eight patients. Follow-up was available for all patients, 13 of whom (81%) were alive and free of disease or had died of unrelated causes over periods ranging from 2-11 years (average, 5.8 years). All 13 of these patients had tumor confined completely to the thyroid gland. One patient died 4 months after diagnosis secondary to sepsis. Two patients (17%) had aggressive biologic courses. In both patients there was extrathyroidal invasion. One of these patients died of metastatic disease to the lungs 3 years after diagnosis; the other was alive with bilateral pulmonary metastases 9 years after the diagnosis. CONCLUSIONS: The findings of the current study indicate that thyroid papillary carcinoma of columnar cell type is a distinct morphologic type but not a distinct clinical type of thyroid papillary carcinoma. The biologic behavior of this tumor is predicated on clinical stage, with the presence or absence of extrathyroidal invasion being the single most important parameter. Treatment of patients with these tumors should be based on the clinical stage and not on the morphologic appearance.

Primary smooth muscle tumors of the thyroid gland.

BACKGROUND: Primary smooth muscle tumors of the thyroid gland are rare. To date, there are few cases reported of primary thyroid leiomyomas and leiomyosarcomas. METHODS: One leiomyoma and four leiomyosarcomas arising within the thyroid gland were identified in the files of the Endocrine Tumor Registry of the Armed Forces Institute of Pathology. Histologic and immunohistochemical features were reviewed and follow-up obtained. RESULTS: The patients included 2 females, ages 56 and 64 years, and 3 males, ages 45, 68, and 83 years. The patients presented with a mass in the thyroid gland that had increased in size over a number of months. All the tumors originated within a single lobe of the thyroid gland and measured from 1.1 to 9 cm in greatest dimension. Histologically, there was a fascicular pattern of growth comprised of spindle-shaped cells with blunt-ended nuclei. The leiomyoma was encapsulated, cytologically bland, and amitotic; the leiomyosarcomas were invasive with increased cellularity, pleomorphism, a high mitotic rate, necrosis, and hemorrhage. Immunohistochemical staining showed reactivity with vimentin, smooth muscle actin, muscle specific actin, and desmin. The patient with the leiomyoma was alive without evidence of disease 11 years after the initial presentation, with surgical resection as the only treatment. Three of the patients with leiomyosarcomas were dead within 2 years of diagnosis, in spite of aggressive therapeutic intervention. The remaining patient was still alive 10 months after initial presentation with multiple lung metastases. CONCLUSIONS: Smooth muscle tumors of the thyroid gland are distinctive tumors. Leiomyosarcomas can be distinguished from anaplastic carcinoma, although patient outcome is uniformly unfavorable.

Intraductal oncocytic papillary neoplasms of the pancreas.

We describe the clinical and pathologic features of 11 intraductal oncocytic papillary neoplasms of the pancreas, a hitherto unrecognized tumor. The patients were six men and five women, and most of the tumors were in the head (head: body/tail = 8:3). The mean patient age was 62 (range, 39-78), and the average tumor size was 6 cm. Grossly the tumors exhibited mucin-filled cysts containing nodular papillary projections. Dilated ducts communicating with the main tumor were sometimes noted. Microscopically the cystic structures appeared to represent dilated ducts containing intraductal tumor. The tumors were characterized by variably complex, arborizing papillary structures. The papillae had thin, delicate fibrovascular cores with focal myxoid changes and were lined by stratified oncocytic cells. Goblet cells and intra-epithelial mucin-containing lumina were present, the latter resulting in a characteristic cribriform pattern. The exuberance of the epithelial proliferation varied from case to case and between different regions within individual tumors; solid sheets of cells were often identified. Although the degree of cytologic atypia was not generally severe, the complexity of the architecture justified a designation of intraductal oncocytic papillary carcinoma in 10 of the 11 cases. In nine cases the tumor was entirely intraductal; one case exhibited focal microinvasion and another showed widespread invasive carcinoma, the invasive elements appearing cytologically similar to the intraductal papillary components. The oncocytic cells stained positively with phosphotungstic acid hematoxylin and Novelli stains. Immunohistochemically, all cases stained positively for B72.3, and five cases showed focal, weak luminal membrane staining for carcinoembryonic antigen. Ultrastructurally many of the cells were packed with mitochondria, and mucin was also identified. Seven patients were alive and free of tumor from 1 month to 3 years (average, 1 year) after resection. Two patients died postoperatively. The remaining two patients died with no evidence of disease at 2.5 and 5 years, the latter following a recurrence at 2.5 years. We conclude that intraductal oncocytic papillary neoplasm is a distinctive pancreatic tumor that is usually intraductal but may develop invasive carcinoma and should be treated with complete resection.

Solid and papillary epithelial neoplasm of the pancreas: imaging-pathologic correlation on 56 cases.

PURPOSE: To evaluate the clinical, pathologic, and imaging findings of solid and papillary epithelial neoplasm (SPEN) of the pancreas and to correlate imaging and gross pathologic features. MATERIALS AND METHODS: A retrospective review was performed in 56 patients (53 female and three male patients aged 10-74 years [mean age at diagnosis, 25 years]) with pathologically proven SPEN of the pancreas. All patients underwent computed tomography (n = 49), ultrasonography (n = 31), or magnetic resonance (MR) imaging (n = 9). Tumor size, location, and imaging features were evaluated and correlated with gross pathologic and histologic features. RESULTS: Mean transverse diameter of these tumors was 9.0 cm (range, 2.5-17.0 cm). They were localized to the tail (n = 30), head (n = 18), and body (n = 8) of the pancreas. All tumors contained some degree of internal hemorrhage or cystic degeneration, and all were well encapsulated. Areas of hemorrhagic degeneration ranged from solid friable tumor to gelatinous or cystic cavities and therefore demonstrated variable imaging features. Calcification was noted in 16 patients. Fluid-debris levels were noted in 10 patients. CONCLUSION: Imaging studies of SPEN of the pancreas consistently demonstrate variable degrees of hemorrhagic degeneration. Calcification is common. Characteristic fluid-debris levels and signal intensities seen with MR imaging indicate blood products. In the appropriate clinical setting, these findings are useful in making a prospective diagnosis.

Langerhans cell histiocytosis of the thyroid: a series of seven cases and a review of the literature.

Langerhans cell histiocytosis is a rare disorder, with a few reports describing isolated thyroid gland involvement. We report seven cases, which included four females and three males ranging in age from 2 months to 55 years, with a median age of 37 years. Histologically, the cases demonstrated either diffuse or focal involvement of the thyroid gland by Langerhans cell histiocytes, characterized by bean-shaped, lobated, folded nuclei. In association with the histiocytic infiltrate, there was a prominent eosinophilic cellular component, as well as destruction of the thyroid follicles. All cases occurred in a background of lymphocytic thyroiditis. One case demonstrated adenomatoid nodules, whereas another had a microscopic papillary carcinoma. Immunohistochemical staining demonstrated positive reactivity with S-100 protein, lysozyme, and KP-1. Four patients with isolated thyroid disease, treated by surgical resection alone, are alive without systemic disease from 3 to 19 years after initial presentation. The three patients with systemic disease died within 1 year of the initial diagnosis with disease-related complications. Localized disease portends a favorable prognosis as compared to the thyroid involvement as part of systemic disease.

Pancreatoblastoma. A clinicopathologic study and review of the literature.

Pancreatoblastoma is a rare pancreatic tumor with a distinctive histologic appearance that generally affects infants and young children. We have studied 14 cases of pancreatoblastoma and reviewed 41 previously reported examples. Nine of our cases occurred in children (from newborn to 4 years old; mean, 2.4), and five affected adults (from 19 to 56 years old; mean, 40). There were 8 male cases and 6 female cases. Most patients presented with incidental abdominal masses, although pain, weight loss, and obstructive jaundice were present, but rarely. The tumors were very cellular microscopically, with cytologically uniform epithelial cells arranged in sheets and nests. Well-formed acinar structures were a consistent feature, and several cases contained ectatic ductular formations, rarely exhibiting intracellular mucin. Consistently present were squamoid corpuscles: circumscribed, whorled nests of plump spindle cells with a squamous appearance and occasional keratinization. The stroma was moderate to abundant and frequently quite cellular (especially in the pediatric cases). By immunohistochemistry, the tumors exhibited acinar, endocrine, and ductal differentiation, with positivity for pancreatic enzymes (100%), endocrine markers (82%), and carcinoembryonic antigen (85%). Ultrastructural examination most commonly revealed acinar differentiation, although mucigen granules and neurosecretory granules were also occasionally found. The behavior was variable: 36% of patients developed metastases, especially to the liver. The adult patients did poorly: three of five died of tumor (mean survival, 18 months), and two were alive at 5 and 15 months, respectively. In contrast, five of the six evaluable pediatric patients were alive from 22 months to 22 years after diagnosis, and only one died of tumor after 16 months. Good responses to chemotherapy were noted in the pediatric group.

Primary mucoepidermoid carcinoma of the thyroid gland: a report of six cases and a review of the literature of a follicular epithelial-derived tumor.

Primary mucoepidermoid carcinomas of the thyroid gland are uncommon tumors of low-grade malignant potential. We report six cases of thyroid mucoepidermoid carcinoma, four occurred in women and two in men with an age range of 29 to 57 (median, 46 years). The clinical presentation was that of a painless mass. Radiographic studies showed a single, solid, "cold" nodule in either the right or left lobe, or isolated to the isthmus. There was no history of a mucoepidermoid carcinoma developing in more typical locations (eg, salivary gland) in any of the patients. Histologically, the tumors were characterized by an intimate admixture of squamoid/epidermoid cells and mucocytes. The tumors were delineated but not encapsulated with prominent cyst formation and a variable amount of associated fibrosis. The squamoid component showed horny pearl formation, individual cell keratinization and/or the presence of intercellular bridges. Intracytoplasmic and luminal epithelial mucin was observed in all cases. In three of the cases a prominent eosinophilic cellular infiltrate was intimately identified within the neoplastic proliferation. One other case was noteworthy for the presence of ciliated epithelium. In all of the cases the uninvolved thyroid tissue showed the presence of lymphocytic thyroiditis. Rare foci of squamous metaplasia were observed in two of the cases. A microscopic focus of thyroid papillary carcinoma was observed adjacent to the mucoepidermoid carcinoma in one case. Immunohistochemical evaluation of the mucoepidermoid carcinoma showed the following antigenic profile: cytokeratin (five of five), CAM 5.2 (four of four), thyroglobulin (five of six), calcitonin (none of six), chromogranin (none of six), polyclonal carcinoembryonic antigen (four of four), and monoclonal carcinoembryonic antigen (none of five). Surgical excision was the treatment of choice. All of the patients reported are alive without disease (recurrence or metastasis) over periods ranging from 1 to 15 years. Based on our findings, we believe that these tumors are of low-grade malignant potential and originate from thyroid follicular epithelial cells rather than from solid cell nests of the ultimobranchial body.

Evaluation of the impact of intraobserver variability on endometrial dating and the diagnosis of luteal phase defects.

OBJECTIVE: To determine the magnitude of intraobserver variation in dating endometrial biopsies and its impact on clinical management. DESIGN: Blinded histopathologic interpretation of endometrial biopsy specimens 1 year apart by five pathologists. SETTING: Large military tertiary care center. PATIENTS: Endometrial biopsy specimens from 51 patients undergoing evaluation for potential luteal phase defects. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Calculation of the magnitude of the individual and overall intraobserver variation in endometrial dating for the five pathologists and estimation of its potential impact on clinical management. RESULTS: The intraobserver variation was 0.69 +/- 0.05 days (means +/- SE). There was no significant difference in the magnitude of the variation for 1-day or 2-day dating ranges. The theoretical probability of altering clinical management by having the same pathologist redate a given specimen ranged from 15% to 28%. CONCLUSION: Histologic dating of endometrial biopsies is subject to a small but highly clinically significant intraobserver variability that may have a major impact on clinical management.

Echovirus meningomyeloencephalitis with administration of intrathecal immunoglobulin.

Echovirus meningomyeloencephalitis was treated with cerebral intraventricular immunoglobulin. This case includes a complete examination of the central nervous system (CNS) supported by viral culture studies, immunoperoxidase staining and electron microscopy. Neuronal loss was most severe in the cerebellum and spinal cord. This may lead to the ataxia and a poliomyelitis-like syndrome often seen in cases of echovirus meningomyeloencephalitis. Focal encephalitic lesions, antigen-antibody reactions and live virus were found at numerous levels of the CNS in spite of intrathecal and intravenous immunoglobulin therapy. This mode of therapy and the electron microscopic features noted in echovirus infections are discussed.