Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma.

The histopathologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPCA) can be difficult. Recent reports have suggested that this neoplasm may be frequently overdiagnosed by pathologists. We examined the observer variation in the diagnosis of FVPCA in 87 tumors by 10 experienced thyroid pathologists. The criteria that the reviewers considered most helpful for making a diagnosis of FVPCA were also assessed. A concordant diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 39%. In this series, 24.1% of the patients had metastatic disease (n = 21). In the cases with metastatic disease, a diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 66.7%, and 7 of the reviewers made a diagnosis of FVPCA with a cumulative frequency of 100%. The most important criteria used to diagnose FVPCA included the presence of cytoplasmic invaginations into the nucleus (pseudo-inclusions), abundant nuclear grooves, and ground glass nuclei. These results suggest that although the diagnosis of FVPCA is variable even among experienced thyroid pathologists, most reviewers agreed on this diagnosis for patients with metastatic disease. The use of well-defined histopathologic features should improve the consistency in diagnosing FVPCA. Since most cases with metastatic disease had obvious invasion, caution should be used in making a diagnosis of FVPCA in the absence of the major histopathologic features or clear-cut invasive growth.

Clusterin expression distinguishes follicular dendritic cell tumors from other dendritic cell neoplasms: report of a novel follicular dendritic cell marker and clinicopathologic data on 12 additional follicular dendritic cell tumors and 6 additional interdigitating dendritic cell tumors.

While tumors of dendritic cell lineage may have overlapping histomorphologic features, most but not all cases can be classified using an immunohistochemical panel, including CD21, CD23, CD35, CD1a, and S-100. Based on observations that clusterin is expressed in benign follicular dendritic cells, clusterin expression in 32 dendritic cell tumors was evaluated. Diffuse strong staining for clusterin was seen in 12 of 12 follicular dendritic cell tumors. Two of these cases were negative for traditional markers (CD21, CD23, CD35); they were classified based on characteristic ultrastructural features. Three of 6 interdigitating dendritic cell tumors were negative for clusterin and 3 showed focal weak positivity. Clusterin staining in Langerhans cell histiocytosis ranged from negative (6 of 14) to weak/moderate (8 of 14). Follicular dendritic cell tumors behaved as benign tumors or low-grade sarcomas. Interdigitating dendritic cell tumors demonstrated a widely variable behavior, ranging from benign to rapidly fatal disease. Based on this initial study, strong clusterin staining supports a diagnosis of follicular dendritic cell tumor. Thus, staining for clusterin is useful in classification of dendritic cell tumors, particularly when the more common markers of follicular dendritic cells are not expressed.

Myeloma of the jaw bones: a clinicopathologic study of 33 cases.

BACKGROUND: A clinicopathologic study of 33 cases of plasma cell neoplasm of the jaw bones was performed. METHODS: The Mayo Clinic's pathology files through 1995 were reviewed for cases of plasma cell neoplasia involving the jaw bones. Clinical data, radiologic features, and follow-up data were obtained from the hospitals of origin, referring physicians, and Mayo Clinic files. The histopathologic features of the 33 tumors were studied. RESULTS: There were 21 (64%) male and 12 (36%) female patients, ranging in age from 25 to 81 years (mean, 57.7 years). Twenty-one tumors (64%) were classified as solitary plasmacytoma of bone (SPB) and 12 (36%) as multiple myeloma (MM). Among the SPB cases, 15 (71%) involved the maxilla, and 14 patients were men, with a mean age of 57.1 years. Abnormal serum protein was found in 22% of patients, and in nine patients (43%) the SPB converted to MM after a median of 20.7 months. Among the MM cases, seven (58%) affected the maxilla, seven patients were men with mean age of 58.3 years, and abnormal serum protein and Bence-Jones protein were found in 42% and 73% of the patients, respectively. Anaplastic histology was identified in seven (33%) SPB and six (50%) MM tumors, and amyloid was present in eight (38%) SPB and three (25%) MM tumors. Twelve (57%) SPB patients died of the disease after a median disease-free survival of 6.75 years, and the overall and disease-free survival rates at 5 and 10 years were 52%, 33%, 33%, and 24%, respectively. All MM patients died of the disease after a median survival of 17.6 months, and the 5-year and 10-year survival rates were 8% and zero. Eighty-six percent of the SPB patients with anaplastic histologic findings died of the disease (average survival, 3.8 years), whereas only 43% of those with classic histologic findings died of the disease (average survival, 11.75 years). Among MM patients, anaplastic histologic findings were associated with a 9-month average survival (26-month average survival for MM patients with classic histologic findings). CONCLUSIONS: SPB patients seem to have a better prognosis than MM patients, and 43% of SPB tumors convert to MM after an average of 20.7 months. Anaplastic histologic findings seem to be associated with lower survival rates and periods for SPB patients and lower survival periods for MM patients.

Clusterin is widely expressed in systemic anaplastic large cell lymphoma but fails to differentiate primary from secondary cutaneous anaplastic large cell lymphoma.

A recent study by Wellmann et al (Blood. 2000;96:398-404) detected clusterin expression in all 36 systemic anaplastic large cell lymphomas (ALCLs) tested, but not in any of 9 primary cutaneous ALCLs. Our purpose was to confirm the diagnostic usefulness of clusterin in systemic ALCL and to evaluate its efficacy in distinguishing primary cutaneous ALCL from secondary skin involvement by systemic ALCL. We examined clusterin expression by paraffin immunohistochemical analysis in 41 systemic ALCLs (18 ALK-1+ and 23 ALK-1-), 9 primary cutaneous ALCLs, and 4 secondary cutaneous ALCLs. Clusterin was positive in 95% of systemic ALCLs (39/41), including 100% (18/18) of the ALK-1+ cases and 91% (21/23) of the ALK-1- cases. Five (56%) of 9 primary and 3 (75%) of 4 secondary cutaneous ALCLs were positive for clusterin. Our observations confirm the diagnostic usefulness of clusterin in systemic ALCL, especially in the ALK-1- cases. However, our data fail to demonstrate its value in distinguishing primary from secondary cutaneous ALCL.

Desmoplastic small round cell tumor: a clinicopathologic, immunohistochemical, and molecular study of 32 tumors.

Desmoplastic small round cell tumor is a rare, aggressive neoplasm that mainly affects young male patients and is characterized by a reciprocal translocation t(11;22)(p13;q12) associated with the EWS-WT1 gene fusion transcript. Clinical, histopathologic, immunohistochemical, and molecular genetics features were reviewed for 32 tumors. There were 29 male and three female patients, with ages from 6 to 54 years (mean, 25 years). The main clinical signs and symptoms included abdominal pain (eight patients), weight loss (five patients), and presence of umbilical hernia (four patients). Two tumors primarily involved the ethmoid sinus and the soft tissues of the scalp; the other tumors (mean size, 10 cm) involved the abdominal cavity (88%). One patient presented initially with an axillary lymph node metastasis. Generally, all tumors showed the typical histologic findings of variably sized clusters of small, round, or spindled cells lying in a desmoplastic stroma. The neoplastic cells in formalin-fixed, paraffin-embedded tissue sections were positive for desmin (dot pattern) (81% of the cases), WT1 (91%), keratin (87%), neuron-specific enolase (84%), CD99 (23%), and actin (3%). The EWS-WT1 gene fusion transcript was detected in 29 of 30 tumors. One tumor with typical clinicopathologic and immunohistochemical features did not show the gene fusion. Follow-up for 27 patients showed that 19 patients (70%) died of uncontrolled, local, or widespread metastatic disease 3-46 months (mean, 20 months) after diagnosis, and eight patients were alive with known evidence of disease. Occasionally, desmoplastic small round cell tumor lacks the classic clinical, histologic, and immunohistochemical features. This study emphasizes the utility of analysis of the EWS-WT1 gene fusion transcript, which was performed on paraffin-embedded tissues, to confirm the diagnosis.

Sinonasal desmoplastic small round cell tumor: a case report.

A case of sinonasal desmoplastic small round cell tumor in a 21-year-old woman is presented. The tumor possessed the diagnostic histologic, immunohistochemical, and genetic characteristics of desmoplastic small round cell tumor. Histologically, the tumor was composed of nests of tumor cells surrounded by a desmoplastic stroma. Immunohistochemical staining was positive for keratin, vimentin, desmin, and, focally, neuron-specific enolase. The desmin immunopositivity was of a classic dot-like perinuclear pattern. RT-PCR analysis showed the fusion transcript resulting from the t(11;22)(p13;q12) reciprocal translocation. This case of sinonasal desmoplastic small round cell tumor, the third reported case not associated with a serosal surface, further obscures the nature and histogenesis of this entity.