Utility of BRAF V600E immunohistochemistry in the diagnosis of mandibular ameloblastomas.

Ameloblastoma, odontogenic keratocyst (OKC), and dentigerous cyst (DC) can have similar radiographic and histological appearances. The purpose of this study was to determine the utility of BRAF immunohistochemistry in discerning mandibular ameloblastomas from OKCs and DCs. This retrospective cohort study included patients treated between 1998 and 2018. Inclusion criteria include incisional biopsy-proven mandibular ameloblastoma, OKC, or DC, and sufficient tissue for immunohistochemistry. The primary predictor variable was the type of lesion. The primary outcome variable was the presence/absence of BRAF V600E immunoreactivity. The cohort consisted of 43 patients (19 female, 24 male; mean age 48 ± 17 years). There were 22 ameloblastomas, 11 OKCs, and 10 DCs. Among ameloblastomas, 68.2% (15/22) stained positive for BRAF V600E; no OKC or DC was positive (P < 0.001). By subtype, the majority of the follicular (83.3%), unicystic (83.3%), desmoplastic (66.7%), and acanthomatous (100%) subtypes were positive, but only 33.3% of the plexiform subtype were positive. BRAF immunohistochemistry may be a useful adjunct in the differentiation of ameloblastoma from OKCs and DCs on incisional biopsies. It may be particularly useful for small samples with a prominent cystic component or equivocal histopathology. Mandibular lesions that are BRAF immunohistochemistry positive are unlikely to be DCs or OKCs.

Clear cell carcinoma: a comprehensive literature review of 254 cases.

This comprehensive literature review represents a summary of all cases of clear cell carcinoma (CCC) of the salivary glands that are documented in the literature. PubMed was used to collect available reports of CCC; 97 reports detailing 254 cases, published between 1983 and 2020, were retrieved. Clinically the tumor manifests most commonly as a painless mass or swelling on the palate, and the duration of symptoms prior to seeking care ranges from 1 week to 6 years. Metastasis, both local and distant, was reported in 13.9% of 202 total cases. Local tumor recurrence was present in 18.8% of the cases. By histopathology, CCC shows a mixture of growth patterns including solid (25.1%), nested (78.6%), sheet-like (23.5%), cords (46.1%), and trabeculae (42.4%). Immunohistochemical studies are positive for one or more cytokeratins (99.1%), PAS (95.1%), EMA (77.8%), and p63 (96.3%), but negative for S-100 (96.3%), PASD (91.1%), SMA (91.0%), and calponin (95.1%). Molecular features were reported in 115 cases; 96.0% were positive for an EWSR1 rearrangement by EWSR1 break apart FISH testing and 14.8% were positive for the rearrangement EWSR1-ATF1 tested by qPCR or targeted RNA sequencing. Clinical patterns and genetic studies imply that this tumor is the extraosseous counterpart of clear cell odontogenic carcinoma, an intraosseous odontogenic tumor of the jaws.

Comparison of Intraoperative Sonography and Histopathologic Evaluation of Tumor Thickness and Depth of Invasion in Oral Tongue Cancer: A Pilot Study.

BACKGROUND AND PURPOSE: For primary squamous cell carcinoma of the oral tongue, accurate assessment of tumor thickness and depth of invasion is critical for staging and operative management. Currently, typical imaging modalities used for preoperative staging are CT and MR imaging. Intraoperatively, CT or MR imaging cannot provide real-time guidance, and assessment by manual palpation is limited in precision. We investigated whether intraoperative sonography is a feasible technique for assessment of tumor thickness and depth of invasion and validated its accuracy by comparing it with histopathologic evaluation of the resected specimen. MATERIALS AND METHODS: Twenty-six patients with squamous cell carcinoma of the oral tongue who underwent tumor resection by a single surgeon between March 31, 2016, and April 26, 2019, were prospectively identified. Intraoperative sonography was obtained in planes longitudinal and transverse to the long axis of the tumor. Twenty-two patients had archived images that allowed measurements of tumor thickness and depth of invasion sonographically. Two patients had dysplasia and were excluded. The remaining 20 patients had histologic tumor thickness and histologic depth of invasion measured by a single pathologist. RESULTS: The mean sonographic tumor thickness was 7.5 ± 3.5 mm, and the mean histologic tumor thickness was 7.0 ± 4.2 mm. Mean sonographic depth of invasion and histologic depth of invasion were 6.6 ± 3.4 and 6.4 ± 4.4 mm, respectively. There was excellent correlation between sonographic and histologic measurements for both tumor thickness and depth of invasion with Pearson correlation coefficients of 0.95 (95% CI, 0.87-0.98) and 0.95 (95% CI, 0.87-0.98), respectively. CONCLUSIONS: Intraoperative sonography can provide reliable, real-time assessment of the extent of tongue tumors.

Clear cell odontogenic carcinoma: a rare jaw tumor. A summary of 107 reported cases.

The purpose of this study was to summarize the currently published cases of clear cell odontogenic carcinoma (CCOC). The PubMed and Springer databases were used to collect available reports, searching for 'clear cell odontogenic carcinoma', 'CCOC', or 'clear cell ameloblastoma'. The search resulted in 75 reports detailing 107 cases between 1985 and 2018. Clinically the tumor manifests as a swelling in the posterior mandible (n=46), anterior mandible (n=33), and maxilla (n=28). Radiological analysis of 85 cases typically showed a poorly defined expansive radiolucency (n=83). Of the 70 patients with symptoms reported, 44 specified a swelling, 11 tooth mobility, seven gingival/periodontal issues, five numbness, and three decreased jaw opening. One patient presented with a neck mass. The duration of symptoms prior to seeking care was specified for 52 patients: 2 months to 1 year for 34 patients, 1-2 years for seven, 2-4 years for two, 4-7 years for six, and 7-12 years for three. The incidence of recurrence appeared to be 38 of the 88 cases where recurrence was reported. CCOC can be distinguished from other oral cancers by its distinctive histology and immunohistochemical characteristics and less aggressive behavior. Currently, treatment should be early and aggressive resection with clear surgical margins and long-term follow-up. The overall goal is to collect a cohort of patients.

FNA diagnosis of poorly differentiated thyroid carcinoma. A review of the recent literature.

Poorly differentiated thyroid carcinoma (PDTC) is a follicular cell-derived tumour that was recognised as a distinct entity by the World Health Organisation in 2004. The natural history and pathological features of PDTC are reported to be intermediate between those of well-differentiated and undifferentiated (anaplastic) thyroid carcinomas. Preoperative identification of PDTC could facilitate better initial patient management in many cases, namely more extensive surgery, without any delay. However, according to some experts, a diagnosis of PDTC can only be rendered on histologic specimens based on criteria recommended in the Turin proposal. Although high-grade features (namely necrosis and mitoses) can be recognised in FNA material, other cytomorphological features have limited value for the preoperative diagnosis of PDTC and specific features for a definitive diagnosis of PDTC have not yet been clearly defined. Here, we review the current status and future prospects for cytological recognition of PDTC; we emphasise the features that should raise suspicion of this rare condition in FNA cytology and provide an update on molecular features and management of PDTC. Despite proposed histological criteria for the diagnosis of PDTC, its recognition on routine thyroid cytology presents a notable challenge. Current and future advances in molecular testing could contribute to the cytological diagnosis of PDTC.

Cytologic features of focal papillary thyroid carcinoma arising within follicular adenoma: a masked cytomorphologic analysis of 17 cases.

BACKGROUND/OBJECTIVE: Focal papillary thyroid carcinoma (PTC) arising within a follicular adenoma (PTCFA) represents a clinically significant, but rare, histopathologic subset of papillary carcinomas whose cytologic features have not been well described. This uncommon presentation of PTC may contribute to a subset of thyroid aspirates interpreted as 'atypia of undetermined significance/follicular lesion of undetermined significance' (AUS/FLUS). STUDY DESIGN: Seventeen fine-needle aspiration biopsy (FNAB) cases diagnosed as 'PTCFA' on corresponding surgical excision were identified from the archival records of 2 large academic medical centers. A control group of 40 FNAB comprised of 20 follicular adenomas (FA) and 20 PTC was identified (based on the corresponding surgical pathology diagnosis) for comparison. All 57 FNAB were reviewed in a masked fashion and scored for a series of 31 cytomorphologic features. The intraclass correlation between diagnostic categories and overall agreement between cytopathologists was statistically evaluated. RESULTS: Aspirates of PTCFA were originally diagnosed as 'negative' (n = 3), 'AUS/FLUS' (n = 7), 'suspicious for a follicular neoplasm' (n = 3), 'suspicious for malignancy' (n = 3), and 'malignant' (n = 1). On masked review, the most common cytomorphologic features of PTCFA were a nonmacrofollicular cytoarchitectural pattern (71%), medium-large cell size (74%), and micronucleoli (79%). Intranuclear pseudoinclusions and a papillary architecture were absent in 85 and 88% of the cases, respectively. Relative to the 2 control groups, the PTCFA cases demonstrated overlapping features between FA and PTC for the majority of the 31 examined cytomorphologic features. CONCLUSION: PTCFA represent a rare subset of PTC that is difficult to recognize as PTC by FNAB. Most cases exhibit overlapping features between a benign thyroid nodule and conventional PTC, and they are often interpreted as 'AUS/FLUS'.

Temporal bone giant cell tumour: report of a second primary giant cell tumour of the temporal bone and infratemporal fossa.

OBJECTIVE: To report a second primary giant cell tumour (GCT) of the temporal bone and infratemporal fossa. METHODOLOGY: Medical records were analyzed in the context of the available literature. RESULTS: A 30 year-old male developed a temporal bone GCT with infratemporal fossa extension 12 years after undergoing successful surgical treatment of a GCT of the femur. These tumours were histologically distinct, suggesting the development of a second primary GCT rather than metastatic disease. This case differs from prior reported cases by surgical approach. Complete removal was achieved but required resection of the zygomatic arch and dissection of all upper facial nerve branches. The patient is disease free after 3 years with acceptable functional and cosmetic results. CONCLUSION: Complete resection of GCTs of the temporal bone and infratemporal fossa is advocated. Surgical techniques that allow for visualization of the facial nerve and increase surgical access can enhance overall clinical success.

Hyalinizing clear cell carcinoma: report of eight cases and a review of literature.

Hyalinizing clear cell carcinoma (HCCC) is an extremely rare neoplasm with a female predominance, composed of nests of monomorphic clear cells within a hyaline stroma. This tumor often follows an indolent course and treatment includes wide surgical excision with or without adjuvant radiotherapy. We report eight cases of HCCC identified at two academic institutions in six women and two men, ranging in age from 25 to 86 years. Histologically, all cases demonstrated cords, trabeculae, and nests of monomorphic clear cells as well as cells with eosinophilic granular cytoplasm. Mild cellular atypia was occasionally seen and mitoses were very rare. Seven cases demonstrated a hyalinized stroma, and one case, a myxoid stroma. Immunohistochemically, the tumor cells were positive for epithelial markers and negative for desmin and actin. Seven cases were negative for S-100. Cells were also positive for periodic acid-Schiff and negative for mucin. The important clinicopathologic features and the differential diagnoses of HCCC, as well as a review of the literature are discussed.

Expression of KIT (CD117) in neoplasms of the head and neck: an ancillary marker for adenoid cystic carcinoma.

Adenoid cystic carcinoma is an indolent salivary gland malignancy that is associated with a poor long-term prognosis. The distinction of adenoid cystic carcinoma from other head and neck neoplasms can occasionally be problematic, particularly in small biopsies. Recent studies suggest that KIT (CD117) might be useful as an ancillary marker for adenoid cystic carcinoma; however, the expression of KIT in other benign and malignant head and neck neoplasms, including those that might mimic adenoid cystic carcinoma, has not been well studied. Here we use two different antibodies against KIT to evaluate its expression in a series of 66 adenoid cystic carcinomas compared with its expression in 98 other neoplasms of the head and neck. Overall, 94% (n = 62) of adenoid cystic carcinomas from various anatomic sites and of various histologic subtypes were positive for at least one of the KIT antibodies, and 77% (n = 50) of adenoid cystic carcinoma cases were positive for both antibodies. This contrasted with only 8% (n = 8) of other head and neck neoplasms that were positive for both KIT antibodies (P <.001). It was of note that certain neoplasms, including pleomorphic adenoma, basal cell adenoma, polymorphous low-grade adenocarcinoma, and basal cell carcinoma, that can show histologic overlap with adenoid cystic carcinoma had significantly less KIT immunoreactivity than did adenoid cystic carcinoma (P <.001). In contrast, KIT expression did not reliably distinguish adenoid cystic carcinoma from basal cell adenocarcinoma and basaloid squamous carcinoma (P >.05). The overall sensitivity of the two KIT antibodies for adenoid cystic carcinoma was 82-89%, and the specificity was 87-88%. The findings in this study support the potential use of KIT immunoexpression for distinguishing adenoid cystic carcinoma from many other benign and malignant head and neck neoplasms.

Cytologic diagnosis of gastrointestinal stromal tumor with emphasis on the differential diagnosis with leiomyosarcoma.

BACKGROUND: Gastrointestinal stromal tumor (GIST) has only recently been distinguished histologically and immunochemically from morphologically similar neoplasms of the abdomen. METHODS: The authors reviewed 15 cytologic cases of GIST (14 fine-needle aspiration [FNA] specimens and 1 peritoneal fluid specimen) and compared them with 23 cases of leiomyosarcoma (LMS) arising in the abdomen or pelvis (all FNAs). Immunochemistry (IC) was performed on both the cytologic and subsequent tissue specimens if sufficient specimen was available. RESULTS: Cytologic samples of GISTs typically showed irregularly outlined clusters of uniform spindle cells that were spread easily without crush artifact. The cells had wispy cytoplasm with long, delicate, filamentous extensions (13 cases; 87%). A prominent vascular pattern was common (9 cases; 60%); pleomorphism (1 case; 7%) was uncommon. The LMSs showed three-dimensional, tightly cohesive, sharply marginated syncytia of spindle cells, often with nuclear crush artifact. The cytoplasm/stroma had a distinct wiry, refractile appearance (21 cases; 91%); delicate filamentous cytoplasmic extensions (5 cases; 22%) and prominent vessels (3 cases; 13%) were less common. LMSs more commonly exhibited pleomorphism (14 cases; 61%). Epithelioid cytomorphology, mitoses, and necrosis occasionally were observed in both tumor types. IC for c-kit (on cytologic material) was positive in 10 of 10 cases of GIST (usually diffuse and strong) and 2 of 19 cases of LMS (focal). CD34 positivity favored GIST (4 of 9 cases) over LMS (1 of 19 cases). Smooth muscle actin was positive in 20 of 20 LMSs (strong and diffuse) and 6 of 10 GISTs (usually focal). Desmin was positive in 12 of 20 LMSs and was only focally positive in 1 of 11 GISTs. Correlation of IC results was excellent between cytologic and tissue specimens. CONCLUSIONS: Delicate cytoplasmic processes; a prominent vascular pattern; a lack of nuclear pleomorphism; and a c-kit-positive, desmin-negative immunoprofile are characteristic features of GIST and help distinguish these tumors from LMS in cytologic specimens.

Extensively keratinized squamous intraepithelial lesions of the cervix are difficult to grade.

We tested the hypothesis that extensively keratinized squamous intraepithelial lesions (SILs) are difficult to grade precisely by identifying 100 Papanicolaou smears with a keratinizing SIL that had been originally judged difficult to grade. Of these, 65 were confirmed as low-grade SIL (LSIL) or high-grade SIL (HSIL) on subsequent biopsy. The 65 smears were reviewed independently by 3 cytopathologists who graded each case as LSIL or HSIL (by Bethesda System criteria). The accuracy of the grade was determined by the subsequent biopsy results; accuracy was compared with that of a historic control group of SILs with biopsy follow-up. In the study group, biopsies showed LSIL in 41 cases and HSIL in 24. The mean accuracy for a smear diagnosis of LSIL was 60% for the study group and 92% for the control group. For a smear diagnosis of HSIL, the accuracy was 60% for the study group and 95% for the control group. The overall kappa value for the study group confirmed poor interobserver agreement. Some keratinizing SILs are difficult if not impossible to grade precisely using standard criteria. For such lesions, the diagnosis "SIL, grade cannot be determined due to extensive keratinization" is justified.

Fine-needle aspiration biopsy of papillary thyroid carcinoma: diagnostic utility of cytokeratin 19 immunostaining.

BACKGROUND: Papillary thyroid carcinoma is the most common malignant neoplasm of the thyroid gland, and fine-needle aspiration biopsy (FNAB) often is the initial diagnostic method used in its detection. Prior studies have shown that immunohistochemical staining for various cytokeratins in general, and cytokeratin 19 (CK19) in particular, can be applied as an ancillary technique for diagnosing papillary thyroid carcinoma in histologic specimens. In the current study the authors assessed the diagnostic utility of CK19 to detect papillary carcinoma effectively in cytologic preparations of thyroid FNABs. METHODS: Immunocytochemical staining with CK19 was performed on cytologic aspirates from 37 papillary thyroid carcinomas and 36 other lesions of the thyroid (14 follicular adenomas, 10 multinodular goiters, 5 cases of Hashimoto thyroiditis, 6 oncocytic [Hürthle cell] neoplasms, and 1 follicular carcinoma). All cases included in the study had a corresponding histopathology specimen. RESULTS: Positive immunocytochemical reactivity for CK19 was identified in 34 of 37 papillary carcinomas and in 1 of 36 other thyroid lesions (sensitivity of 92% and specificity of 97%). Although the strongest reactivity was obtained in methanol fixed thin layer preparations, the antibody also was effective in detecting papillary carcinoma in alcohol fixed and air-dried smears. The single false-positive case was a follicular adenoma with focal areas of papillary hyperplasia. All other aspirates including those from cases of Hashimoto thyroiditis, multinodular goiter, follicular adenoma, oncocytic neoplasms, and follicular carcinoma were negative. CONCLUSIONS: CK19 is an effective, highly sensitive, and specific ancillary tool for the diagnosis of papillary carcinoma in thyroid FNABs.

Differentiation of odontogenic keratocysts from nonkeratinizing cysts by use of fine-needle aspiration biopsy and cytokeratin-10 staining.

PURPOSE: In this study, the efficacy of fine-needle aspiration biopsy (FNAB) and cytokeratin 10 immunocytochemical staining to differentiate odontogenic keratocysts (OKC) from dentigerous and other nonkeratinizing cysts was evaluated. PATIENTS AND METHODS: This was a prospective study of 18 FNABs of odontogenic cystic lesions performed at the Massachusetts General Hospital between 1995 and 1998. A consistent and standardized technique was used to obtain the cytologic material. Immunocytochemistry was performed on destained smears by using a monoclonal antibody against cytokeratin 10. Identical immunohistochemical methods were applied to the final surgical specimen, and results were compared. RESULTS: Cells of 10 of 18 FNABs showed a markedly positive immunoreaction to anti-cytokeratin 10, supporting a diagnosis of OKC. In all 10 cases, the diagnosis was confirmed by histology. Six of 18 cases showed an absence of staining and were interpreted as anti-cytokeratin 10 negative. In the 2 remaining cases, there were occasional squamous cells on the smear with weak anti-cytokeratin 10 uptake. The overall pattern was negative, and these were interpreted as nonkeratinizing cysts. In all 8 of these cases, the diagnosis of OKC was excluded based on the immunocytochemistry, and the final histologic diagnoses were: dentigerous cyst (n = 4) and radicular cyst (n = 4). CONCLUSIONS: The combination of FNAB with immunocytochemical determination of cytokeratin 10 expression by sampled epithelial cells was 100% accurate in distinguishing an OKC from a nonkeratinizing odontogenic cyst in this series. The technique allows for early diagnosis and rational surgical planning.

Intratumoral genetic heterogeneity and progression of endometrioid type endometrial adenocarcinomas.

OBJECTIVES: Development of genetic heterogeneity is one mechanism whereby tumors may acquire increasing aggressiveness during neoplastic progression. In this study we relate development of intratumoral genetic heterogeneity to invasion and metastatic spread of sporadic endometrioid (type I) endometrial adenocarcinomas. METHODS: Microsatellite unstable adenocarcinomas underwent detailed microsatellite allelotype mapping with reconstruction of neoplastic lineages using maximum parsimony analysis. RESULTS: Within individual patients, tumor allelotypes sometimes varied between regions of histologically identical tumor, indicating that genotypic variation may reflect differences inapparent by histology. Comparison of noninvasive (surface/luminal) with invasive (myometrial invasion or metastasis) carcinoma showed highly related genotypes in 3/8 cases in which the invasive component can be recognized as evolved from the superficial tumor lineage by progressive clonal selection. In 3/8 cases superficial and invasive genotypes independently evolved different sets of altered microsatellites, indicating either divergence at an early stage in tumor evolution or independent selection events. A total of 2/8 cases had random patterns of marker distribution between sampled areas that were not informative in delineating systematic relationships between surface and invasive tumor. CONCLUSIONS: We conclude from these results that endometrial tumor progression may occur through physical extension of existing clones or through creation of new subclones with altered growth properties. The latter occurs in about half of cases, where myometrial invasion may select for particular clones that are poorly represented on the luminal surface.

Fine-needle aspiration of dedifferentiated chondrosarcoma of the larynx.

We present a case of dedifferentiated chondrosarcoma of the larynx in which the dedifferentiated component was initially diagnosed by fine-needle aspiration (FNA). The patient was a 74-yr-old man who presented with difficulty breathing and an anterior neck mass. A CT scan demonstrated a 4.5-cm cartilaginous lesion involving the left thyroid cartilage, with an anterior soft-tissue component. Nine years prior, the patient had an incomplete resection of a low-grade chondrosarcoma at the same site. FNA was performed on the current lesion, demonstrating a high-grade spindle-cell sarcoma with a storiform pattern. The cytomorphology together with immunocytochemistry and electron microscopy were diagnostic of malignant fibrous histiocytoma (MFH), and synthesis of the clinical, radiographic, and cytomorphologic features resulted in a diagnosis of dedifferentiated chondrosarcoma. The cytologic diagnosis was histologically confirmed by laryngectomy. Although rare, dedifferentiated chondrosarcoma should be included in the differential diagnosis of high-grade sarcomas of bone and cartilage assessed by FNA.

Sporadic microsatellite instability is specific to neoplastic and preneoplastic endometrial tissues.

Microsatellite instability is a frequent (13%-24%) finding in sporadic endometrial adenocarcinoma and its precursor lesions, but most studies are limited to patients who already have malignant or premalignant endometrial disease. We performed retrospective testing for microsatellite instability in women in whom cancers showing microsatellite instability developed later and prospective testing in randomly selected normal and anovular endometrial biopsy specimens. Microsatellite instability in cancer-bearing biopsy specimens accurately reflected that seen in matched malignant tissues obtained at hysterectomy. In 1 patient, microsatellite instability developed in a scanty sample of fragmented endometrial tissues 7 years before the onset of endometrial cancer. Prospective testing for microsatellite instability in the endometria of women unselected for subsequent appearance of endometrial cancer showed a very low rate of microsatellite instability. Only 1 endometrial specimen showing microsatellite instability was found among 75 anovulatory endometrial specimens, and none were found in 377 normal endometrial specimens and 46 polyps examined. Microsatellite instability may precede the onset of histologically diagnosed carcinoma but is rare in randomly sampled histologically normal endometrial tissues.

Dedifferentiated chondrosarcoma of the larynx.

A 74-year-old man with a history of a chondroid lesion of the larynx noted an enlarging neck mass. Axial CT showed a large expansile lesion arising from the left thyroid cartilage. Multiple rings and arcs with relatively intact cortex indicated a chondroid lesion. Irregularity of the anterolateral margin abutted a prominent soft-tissue component. The specimen obtained from fine needle aspiration was suggestive of a malignant fibrous histiocytoma. After further resection, the final diagnosis was dedifferentiated chondrosarcoma. A new soft-tissue component or rapid growth of the mass can be indicative of a diagnosis of dedifferentiated chondrosarcoma.

Endometrial precancer diagnosis by histopathology, clonal analysis, and computerized morphometry.

Management of endometrial precancers is compromised by longstanding debate over the natural history of endometrial hyperplasias and inconsistencies in their diagnosis. The recent demonstration that some hyperplasias, like cancers, are phenotypically monoclonal is useful in recognizing biological precancers. A clonal analysis has been undertaken of a series of 93 endometrial tissues and their morphology has been evaluated by subjective diagnostic classification and computerized morphometric analysis. A pathologist's diagnosis of atypical endometrial hyperplasia was highly associated with monoclonal growth. Both microsatellite-stable and microsatellite-unstable precancers were classified as atypical hyperplasias, indicating overlapping morphologies for these two groups. Diagnosis of non-atypical endometrial hyperplasias was not reproducible and identified a group of lesions equally likely to be monoclonal as polyclonal. Computerized morphometry resolved these lesions into monoclonal and polyclonal subgroups with a high degree of accuracy and reproducibility. The predictive value of morphometry was dominated by that fraction of the sample which consisted of stroma (volume percentage stroma). This can be measured manually and used to predict monoclonality when below the threshold value of 55%. This study shows that morphometric analysis reproducibly and precisely identifies monoclonal endometrial precancers from histological sections. It may serve, furthermore, to classify accurately lesions judged by pathologists as indeterminate (non-atypical hyperplasias). The material from this study (available at www.endometrium.org from March 1, 2000) and precisely defined architectural diagnostic criteria provide new tools for diagnostic standardization of endometrial precancers.

LSIL biopsies after HSIL smears. Correlation with high-risk HPV and greater risk of HSIL on follow-up.

Can the risk associated with a high-grade cervical smear be disregarded when followed by a low-grade biopsy? We examined the distribution of human papillomavirus (HPV) types in such cases to see whether they segregated preferentially with low-risk or high-risk viruses and compared the distribution with that reported in the literature for women with high-grade squamous intraepithelial lesions (HSILs) and low-grade squamous intraepithelial lesions (LSILs). We identified 48 cases of HSIL smears with corresponding LSIL biopsy specimens. Biopsy specimens were tested and typed for HPV by polymerase chain reaction amplification with consensus primers followed by restriction fragment length polymorphism analysis, and HPVs were scored as low-risk or high-risk types. Thirty-seven cases scored positive for HPV DNA: 2 for low-risk HPV types, 17 for high-risk types, and 18 for types of unknown oncogenicity. The prevalence of high-risk HPV was significantly higher than that of low-risk HPV. There was a higher rate of high-risk HPV than that seen in historic unselected LSIL cases. Cases of HSIL cytology/LSIL histology represent a group distinct from unselected LSILs by virtue of their higher prevalence of high-risk HPV types and, therefore, warrant closer clinical follow-up.

Fine-needle aspiration biopsy of intraosseous jaw lesions.

PURPOSE: This study assessed diagnostic accuracy, determined reasons for error, and evaluated modifications to improve the reliability of fine-needle aspiration biopsy (FNAB) of primary jaw lesions. PATIENTS AND METHODS: This was a retrospective review of 32 FNABs of intraosseous jaw lesions performed at the Massachusetts General and Children's Hospital between 1993 and 1998. A consistent, standardized technique was used, and each case was evaluated for 1) adequacy of cells to allow diagnosis, 2) presence of malignant cells, and 3) correlation between FNAB diagnosis and the final histopathology. RESULTS: Material obtained by FNAB was adequate for evaluation in 30 of 32 cases. No complications were reported. Malignant cells were found in 5 of 30 cases. FNAB diagnosis was confirmed by histopathology in all 5 of these specimens (100% accuracy). The FNAB diagnosis of benign lesions was confirmed in 17 of 25 cases (68%). The most common benign lesions were odontogenic cysts, ameloblastomas, and fibro-osseous and giant cell lesions. Incorrect diagnosis was related to lack of architectural context of the FNAB material, sampling of a nonrepresentative part of a large lesion, and inadequate quantity or quality of the aspirate. CONCLUSIONS: FNAB is a useful technique to distinguish between malignant and benign intraosseous jaw lesions. Its simplicity, suitability as an outpatient procedure, rapidity of interpretation, and minimal morbidity potentially make it the diagnostic tool of choice in the hospital setting.