Carol F. Adair

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.

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.

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.

Clinical features associated with metastasis and recurrence of differentiated thyroid cancer in children, adolescents and young adults

Differentiated thyroid cancer (DTC), including papillary (PTC) and follicular (FTC) variants, is unusual in children and accounts for only 10% of all cases. For that reason, knowledge of the clinical features which predict recurrence is limited. We reviewed 170 cases of childhood DTC to determine if specific clinical or pathological findings were associated with increased risk of recurrence.

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.

The impact of initial surgical management on outcome in young patients with differentiated thyroid cancer.

BACKGROUND/PURPOSE It is generally believed that differentiated thyroid cancer (DTC) in young patients has an excellent prognosis. This calls into question the need for more extensive surgical ablation of the thyroid gland with attendant risks of surgical complications. The purpose of this report was to investigate both the incidence of surgical morbidity and the impact of surgery on locoregional recurrence of disease. METHODS The authors reviewed the clinical course of patients under 22 years of age treated for DTC within Department of Defense hospitals since 1950. Data were available for determination of surgical morbidity in 126 and for outcome in 105. RESULTS The incidence of postoperative hypocalcemia was 17% and of recurrent laryngeal nerve injury 3%. Factors predictive of morbidity were (1) more extensive thyroid surgery (P = .023), and (2) the presence of gross tumor invasion (P = .022). The incidence of neck recurrence was analyzed among a cohort of 90 patients. A total of 19 (21%) patients had a local recurrence. The median time to recurrence was 24 months. The factor predictive of recurrence was the presence of gross invasion (P = .0001). A strong trend toward locoregional recurrence was found among patients with metastatic disease to more than five cervical nodes (P < .08). The primary operations on the thyroid and regional nodes were not significant predictors of neck recurrence. Among these 19 patients there have been no deaths, but 25% had persistent disease at a mean follow-up of 12.6 years. CONCLUSIONS The incidence of surgical morbidity does increase with more extensive surgery. Outcome is predicted primarily by the initial extent of disease.

Peripheral Nerve Sheath Tumors of the Thyroid Gland: A Series of Four Cases and a Review of the Literature.

Primary peripheral nerve sheath tumors (PNSTs) of the thyroid gland are exceptionally rare. Two schwannomas and two malignant PNSTs (MPNSTs), arising primarily within the thyroid gland, were identified in the files of the Endocrine Tumor Registry at the Armed Forces Institute of Pathology. The patients included two females, age 69 and 80 yr, and two males, age 18 and 33 yr. The patients presented with a mass in the thyroid gland confined to a single lobe of the thyroid without involvement of the cervical neck region. None of the patients had a history of neurofibromatosis. The benign tumors were encapsulated, one of them cystic, with the characteristic cellular and nuclear features of schwannomas. The MPNSTs were invasive tumors, effacing the thyroid parenchyma, with a fascicular pattern of growth composed of neural appearing cells with increased cellularity, increased mitotic activity and with focal necrosis. Immunoreactivity for S-100 protein and vimentin was seen in all tumors. The patients with schwannomas, treated only by surgical resection, were alive without evidence of disease, over a period of 5–33 yr. Both patients with MPNSTs died of the disease 8 mo and 42 mo, respectively, with widely disseminated disease. Primary thyroid PNSTs are exceptionally rare tumors. MPNSTs, in this limited experience, have a fatal outcome irrespective of aggressive adjuvant therapy.

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.