Cytological diagnosis of follicular dendritic cell sarcoma with a unique pattern of D2-40 immunoexpression.

Fine needle aspiration procedure is routinely used for cytological diagnosis of nodal or extra nodal lesions. Follicular dendritic cell sarcoma (FDCS) is a rare mesenchymal neoplasm arising from follicular dendritic cells of lymphoid follicles at nodal and extranodal sites. Multimodal therapies have emerged for FDCS, necessitating its accurate pathologic diagnosis with additional ancillary testing for directing clinical management. By immunohistochemical analysis, FDCS is positive for the complement receptors CD21, CD23, and CD35. In addition, D2-40 is reported to be highly sensitive for FDCS with a strong membranous pattern of expression. In this study, we present the cytological diagnosis of a case of FDCS in retroperitoneal lymph nodes with an emphasis on a unique staining pattern of D2-40 which showed a strong nuclear pattern in tumor cells comparable to the membranous pattern of D2-40 on the control tissue and other surgical cases of FDCS in our comparative study.

World Health Organization Reporting System for Soft Tissue Cytopathology: Risk of malignancy and reproducibility of categories among observers.

INTRODUCTION: In 2024, the World Health Organization (WHO) is scheduled to publish the WHO Reporting System for Soft Tissue Cytopathology (WHORSSTC). This system establishes categories with well-defined definitions, criteria, and estimated risks of malignancy (ROMs) for soft tissue tumors. The estimates of ROM are based on a relatively small number of published studies. Interobserver reproducibility is not addressed in the reporting system even though reproducibility of a reporting system is highly important. METHODS: A manual search of one authors personal consultation files and teaching set (L.J.L.) was conducted for all cytologic specimens of soft tissue tumors accessioned between January 1, 1985 and December 31, 2022. Only cases with documented surgical pathology follow-up were included in the study. Slides from each case were evaluated independently by three cytopathologists with each case assigned to one of the WHORSSTC categories. A ROM for each of the WHORSSTC categories was calculated. Interobserver agreement was evaluated by the kappa and weighted kappa statistics. RESULTS: Risk for malignancy by category were: Category 1: 0%, Category 2: 28%, Category 3: 57%, Category 4: 47%, Category 5: 63%, and Category 6: 88%. Kappa statistics for agreement between raters varied from 0.2183 to 0.3465 and weighted kappa varied from 0.3778 to 0.5217. CONCLUSIONS: The WHORSSTC showed a progression of malignancy risk from the category "benign" (28%) to the category "malignant" (88%). Interobserver agreement was only fair.

Healers and midwives accused of witchcraft (1563-1736) - What secondary analysis of the Scottish survey of witchcraft can contribute to the teaching of nursing and midwifery history.

BACKGROUND: Nearly 4000 people were accused of witchcraft in Scotland between 1563 and 1736. Some of these were healers, midwives, and nurses. OBJECTIVE: To investigate Scotland's folk-healers and midwives accused of witchcraft and review their work from a nursing and midwifery perspective. DESIGN: Secondary analysis of the Survey of Scottish Witchcraft. METHODS: Those on the Survey with witchcraft accusations relating to folk-healing or midwifery were identified and their biographies were created from Survey data (2021). Individual biographical data were descriptively analysed. Healing/midwifery practice information was tabulated and thematically analysed. RESULTS: 142 individuals were identified (85 % women), 51 % were found guilty, 90 % were executed. Most (98 %) were folk-healers with 10 accused for midwifery reasons. Mainly their work was accused of causing harm. Three themes emerged: their use of rituals; unorthodox religious practices and treatments. Rituals included actions carried out a certain number of times. Religious practices frequently referenced Catholicism. Many of their treatments for ingestion, application or bathing used items still recognised for their health properties. Approximately, 10 % of the 142, mainly in the 1500s/early 1600s, utilised expensive items and complex treatments which had more in common with 'elite' knowledge rather than simple folklore. CONCLUSIONS: Across all 142 people, many aspects of their work are identifiable within more contemporary nursing and midwifery practice including their use of rituals, treatments, and holism. Mostly the accused were folk-practitioners, but a few (1500s/early 1600s) appear to have been healers working akin to physicians. Following the Protestant reformation (1560) their work, unlike that of physicians, was marginalised, considered unorthodox and harmful because they were women and/or their work reflected Catholicism. European hospital nursing originates in the monastic houses, but little is known about these early religious nurses. This study is novel in suggesting that whoever taught these accused witch/healers may have been connected to the monastic hospitals pre-Reformation.

Cytomorphology of spindle cell/sclerosing rhabdomyosarcoma, including MYOD1 (LI22R) mutation result.

Spindle cell/sclerosing rhabdomyosarcoma (RMS), characterized by MYOD1 (L122R) mutation in a subset of cases is a newly described subtype of RMS. Presently, there is no documentation of cytomorphological features, especially of sclerosing RMS. Case 1: A 24-year-old male presented with pain and swelling in his wrist for a one-year duration. MRI revealed a well-defined soft tissue lesion measuring 5.3 cm, encasing the lower end of the ulna. Fine-needle aspiration cytology (FNAC) smears revealed clusters of tumor cells with round to oval to spindle-shaped nuclei, scant to moderate amount of cytoplasm with the wisps of the metachromatic stroma. Histopathological examination revealed a malignant tumor comprising cells with polygonal to spindle-shaped nuclei, arranged in a sclerotic stroma. Immunohistochemically, the tumor cells were positive for desmin, myogenin, and MYOD1. A diagnosis of sclerosing RMS was offered. Furthermore, the tumor revealed MYOD1 (L122R) mutation. Case 2: A 43-year-old male presented with a 4-month history of "nasal stuffiness" and pressure. Imaging revealed a poorly defined infiltrative lesion in his nasal cavity. FNAC smears revealed loose and tightly cohesive clusters of malignant cells with oval to spindle-shaped nuclei, a moderate amount of ill-defined bluish to finely vacuolated cytoplasm, and focal streak artifact with interspersed stromal fragments. Histopathological examination revealed a malignant tumor composed of oval to spindle-shaped nuclei, embedded in a variably hyalinized stroma. Immunohistochemically, the tumor cells were positive for desmin, and myogenin. Diagnosis of spindle cell/sclerosing RMS was offered. The present study constitutes one of the first documentation of cytomorphological features of two rare cases of spindle cell/sclerosing RMS. The differential diagnoses and treatment-related implications are presented.

A case of osteoclastic variant of anaplastic thyroid carcinoma: Diagnostic and prognostic marker studies by cytology.

Anaplastic thyroid carcinoma is an infrequent, but aggressive fatal subtype of thyroid cancer. The osteoclastic variant of anaplastic carcinoma is a rare subtype of anaplastic carcinoma with rare cases reported in the literature. Molecular targeted therapies have emerged for the anaplastic carcinoma, necessitating accurate pathologic diagnosis with additional ancillary testing for directing clinical management. We present here the cytological diagnosis of an anaplastic thyroid carcinoma-osteoclastic variant on fine-needle aspiration (FNA), with emphasis on the novelty of utilizing the least invasive procedure (aspiration cytology) for rendering pathological diagnosis as well as identifying potential prognostic markers for targeted immunotherapy.

Crystals and crystalloids in cytopathology: Incidence and importance.

Many crystals and crystal-like structures may be encountered in cytopathology practice and can represent both beautiful novelties and diagnostic aids. The authors present an organ-specific review of the published literature on crystals combined with personal experiences. The purpose is not only to serve as a reference guide by highlighting the clinical and morphologic features of crystals, crystalloids, and crystal-like structures but also to review their significance and to offer reporting strategies in cases that bear management implications.

Performance of specific morphologic features in distinguishing low-grade squamous intraepithelial lesions from high-grade squamous intraepithelial lesions in borderline cases: a College of American Pathologists Cytopathology Committee multiobserver study.

INTRODUCTION: Distinguishing between low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) can be difficult on certain Papanicolaou (Pap) tests, hindering interobserver concordance. We investigated the variables influencing the interpretation of LSIL versus HSIL in Pap test slides rejected from the College of American Pathologists PAP education program. MATERIALS AND METHODS: Eleven cytologists, who were unaware of the reference interpretation, examined 21 Pap slides (11 submitted as LSIL and 10 as HSIL) rejected from the PAP education program and recorded the number of LSIL cells, HSIL cells, keratinized dysplastic cells, LSIL clusters with mixed HSIL cells, atypical squamous metaplasia, atypical glandular cells, the presence of inflammation or infectious organisms, and the overall interpretation (LSIL or HSIL). We evaluated the significance of these 11 variables using a nonlinear mixed model analysis. RESULTS: LSIL had greater concordance (92 of 121 responses; 76.0% concordance) than HSIL (68 of 110 responses; 61.8% concordance; P < 0.001). The only predictors of misclassified cases were the number of atypical squamous metaplastic cells and the number of HSIL cells (P < 0.001). The more of these cells identified, the more likely the reviewers were to classify the slide as HSIL. The reproducibility of the diagnosis was fair (Gwet's agreement coefficient, 0.33). CONCLUSIONS: Interobserver reproducibility is a challenge for a subset of cases with features intermediate between LSIL and HSIL. Atypical squamous metaplasia and dysplastic nuclei with a nuclear/cytoplasmic ratio greater than one half of the cell volume (HSIL) present on a Pap test influenced the likelihood that a reviewer would interpret the case as HSIL rather than LSIL.

PD-L1 expression in sarcomas: An immunohistochemical study and review of the literature.

BACKGROUND: Immunotherapy is increasingly used for treatment of metastatic melanoma and carcinomas. PD-1 (programmed death 1) and its associated ligand (PD-L1) inhibits the activation of T-lymphocytes. This inhibition can be impacted by a number of drugs. Response to these drugs is predicted by assessment of PD-L1 expression. PD-L1 expression varies between 19% and 92% in melanomas and carcinomas. PD-L1 expression is less well documented for sarcomas. DESIGN: Fifty-six sarcomas of various histopathologic types were immunohistochemically stained (IHC) for PD-L1 using the antibody clone SP263 (Ventana, Tuscan, AZ). Membrane staining of tumor cells was quantitated as a percentage of total tumor cells. Sarcomas were judged as non-expressors (less than 1%) low-expressors (1 to 50%) and high expressors (greater than 50%). The percentage of each type of sarcoma judged as an expressor was determined. RESULTS: Table 1 documents the percentage of each type of sarcoma expressing PD-L1. 14% of sarcomas expressed PD-L1. Percentage of sarcomas expressing PD-L1 varied significantly between types but the majority of sarcomas were non-expressors. CONCLUSION: PD-L1 IHC expression is valuable in predicting response to immune-modulating drugs. Such therapies may be useful for treatment of metastatic sarcomas. Expression of PD-L1 in carcinomas and melanomas is variable ranging from 19% to 92%. In our study, a minority (14%) of sarcomas expressed PD-L1. Other studies have shown similar results with between 1.4 and 59% (average 24%) of sarcomas expressing PD-L1. Expression appears to be sarcoma type specific. These finding suggest that PD-L1 based therapy may be less useful in sarcomas than in other malignancies.

Myxoid neoplasms of bone and soft tissue: a pattern-based approach.

INTRODUCTION: The accurate diagnosis of musculoskeletal neoplasms is difficult but a pattern-based approach combined with ancillary testing has been shown to improve diagnostic accuracy. The pattern-based approach is particularly appropriate for myxoid lesions. MATERIALS AND METHODS: The authors reviewed their personal experience of over 3 decades of diagnosing myxoid neoplasms of musculoskeletal lesions. RESULTS: The authors found that myxoid lesions can be accurately classified based on cell type, nuclear atypia, presence of blood vessel fragments, as well as the results of immunohistochemical and molecular testing. CONCLUSIONS: Musculoskeletal lesions with a prominence of myxoid or chondroid material in the background can be accurately diagnosed using pattern analysis and ancillary testing.

Giant Cell Tumor of Bone With Cartilage Matrix: A Clinicopathologic Study of 17 Cases.

Giant cell tumor of bone (GCT) is a benign locally aggressive neoplasm composed of mononuclear cells admixed with innumerable osteoclast-type giant cells. H3F3A gene mutations producing mutant histone protein product H3.3 have been identified in 96% of GCT; mutant H3.3 is reliably demonstrated by immunohistochemistry. GCT may contain woven bone and rarely, neoplastic cartilage nodules which causes diagnostic challenges with aggressive neoplasms such as osteosarcoma. We describe the features of GCT with cartilage matrix and report the next-generation sequencing findings in a subset of tumors. Seventeen cases of GCT with cartilage matrix form the cohort: 7 males and 10 females, 13 to 55 (mean: 25) years old. Tumors involved the fibula (6), femur (6), and patella, tibia, humerus, S1, and scapula (1 case each). Tumors were radiolucent, circumscribed, lytic, and expansile. All contained classic GCT, foci of cartilage matrix, and trabeculae of woven bone. Immunohistochemistry showed diffuse staining for H3.3 in 9/9 cases and 1 case was positive for S100 and SOX9 in the cartilage areas. Next-generation sequencing showed a mutation in the H3F3A gene in 6/6 cases. On follow-up, 2 patients who underwent resection showed no disease after 12, and 7 months, respectively. Three patients had recurrences 10, 12, and 27 months after curettage; there were no metastases. GCT with cartilage matrix is uncommon. The cartilage matrix is associated with woven bone suggesting the neoplastic cells may differentiate into chondrocyte-like and osteoblast-like cells. Recognition of this neoplasm is important to prevent misdiagnosis and overtreatment of affected patients.

Incidence and clinical relevance of non-small cell lung cancer lymph node micro-metastasis detected by staging endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND: Approximately twenty percent of lymph node (LN) negative non-small cell lung cancer (NSCLC) patients who undergo curative intent surgery have pan-cytokeratin immunohistochemistry (IHC)-detectable occult micro-metastases (MMs) in resected LNs. The presence of the MMs in NSCLC is associated worsened outcomes. As a substantial proportion of NSCLC LN staging is conducted using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), we sought to determine the frequency of detection of occult MMs in EBUS-TBNA specimens and to evaluate the impact of MMs on progression-free and overall survival. METHODS: We performed retrospective IHC staining for pan-cytokeratin of EBUS-TBNA specimens previously deemed negative by a cytopathologist based on conventional hematoxylin and eosin staining. The results were correlated with clinical variables, including survival outcomes. RESULTS: Of 887 patients screened, 44 patients were identified meeting inclusion criteria with sufficient additional tissue for testing. With respect to the time of the EBUS-TBNA procedure, 52% of patients were clinical stage I, 34% clinical stage II, and clinical 14% stage IIIa NSCLC. Three patients (6.8%) were found to have cytokeratin positive MMs. All 3 MMs detected were at N2 LN stations. The presence of MMs was associated with significantly decreased progression-free (median 210 vs. 1,293 days, P=0.0093) and overall survival (median 239 vs. 1,120 days, P=0.0357). CONCLUSIONS: Occult LN MMs can be detected in EBUS-TBNA specimens obtained during staging examinations and are associated with poor clinical outcomes. If prospectively confirmed, these results have significant implications for EBUS-TBNA specimen analyses and possibly for the NSCLC staging paradigm.

Low-Grade Squamous Intraepithelial Lesion or High-Grade Squamous Intraepithelial Lesion? Concordance Between the Interpretation of Low-Grade Squamous Intraepithelial Lesion and High-Grade Squamous Intraepithelial Lesion in Papanicolaou Tests: Results From the College of American Pathologists PAP Education Program.

CONTEXT.­: Obtaining diagnostic concordance for squamous intraepithelial lesions in cytology can be challenging. OBJECTIVE.­: To determine diagnostic concordance for biopsy-proven low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Papanicolaou test slides in the College of American Pathologists PAP Education program. DESIGN.­: We analyzed 121 059 responses from 4251 LSIL and HSIL slides for the interval 2004 to 2013 using a nonlinear mixed-model fit for reference diagnosis, preparation type, and participant type. We evaluated interactions between the reference diagnosis and the other 2 factors in addition to a repeated-measures component to adjust for slide-specific performance. RESULTS.­: There was a statistically significant difference between misclassification of LSIL (2.4%; 1384 of 57 664) and HSIL (4.4%; 2762 of 63 395). There was no performance difference between pathologists and cytotechnologists for LSIL, but cytotechnologists had a significantly higher HSIL misclassification rate than pathologists (5.5%; 1437 of 27 534 versus 4.0%; 1032 of 25 630; P = .01), and both were more likely to misrepresent HSIL as LSIL ( P < .001) than the reverse. ThinPrep LSIL slides were more likely to be misclassified as HSIL (2.4%; 920 of 38 582) than SurePath LSIL slides (1.5%; 198 of 13 196), but conventional slides were the most likely to be misclassified in both categories (4.5%; 266 of 5886 for LSIL, and 6.5%; 573 of 8825 for HSIL). CONCLUSIONS.­: More participants undercalled HSIL as LSIL (false-negative) than overcalled LSIL as HSIL (false-positive) in the PAP Education program, with conventional slides more likely to be misclassified than ThinPrep or SurePath slides. Pathologists and cytotechnologists classify LSIL equally well, but cytotechnologists are significantly more likely to undercall HSIL as LSIL than are pathologists.

The Papanicolaou Society of Cytopathology guidelines for respiratory cytology: Reproducibility of categories among observers.

INTRODUCTION: The Papanicolaou Society of Cytopathology (PSC) has developed a set of guidelines for reporting respiratory cytology. While the malignancy risk for each category is known, the interobserver reproducibility of these diagnostic categories has not been well described. METHODS: Fifty-five cytologic specimens obtained by fine needle aspiration from the pulmonary nodules were independently reviewed by four board-certified cytopathologists and assigned to the diagnostic categories described by the PSC guidelines for respiratory specimens. Statistical analysis for diagnostic accuracy was performed for absolute agreement and chance-corrected agreement (kappa). Differences in frequency of distribution of diagnoses between raters were assessed using the Kruskal-Wallis test. RESULTS: No significant differences in distribution of scores by raters were observed. On average, the absolute agreement was 49.5% and the chance-corrected agreement (kappa) was 20%. 34.5% of interrater comparisons were in full agreement, and total lack of agreement between the four categories was found in 3% of cases. Combining the "suspicious for malignancy" category with the "malignant" category did not significantly alter interrater agreement statistics. CONCLUSIONS: The PSC categories showed only fair reproducibility among four cytopathologists. Agreement between raters was at best fair and did not improve significantly when the categories "suspicious for malignancy" and "malignant" were combined. The most common source of disagreement appeared to be between the categories "suspicious" and "malignant."

CIC-DUX4 sarcoma diagnosed by fine-needle aspiration cytology: A case report.

The CIC-DUX4 sarcoma is a small round blue cell sarcoma which presents like extraskeletal Ewing sarcoma, but is negative for the EWSR1 gene translocation. The recognition of CIC-DUX4 sarcomas as an aggressive sarcoma may be challenging in fine needle aspirates or small needle core biopsies. We present a case of a 13-year-old female with a fine needle aspiration (FNA) and core needle biopsy (CNB) of a thigh mass showing CIC-DUX4 sarcoma. Cytologic findings include tumor cells with high nuclear to cytoplasmic (N:C) ratio, eccentric nuclei and small nucleoli. The tumor cells were arranged in sheets and singly dispersed with background necrosis. Mitotic figures and apoptosis were present. These findings are similar to cases previously reported. Other reported findings of spindled nuclei, clear cell change and lobular growth pattern were not seen in our case. Immunohistochemical stains showed tumor cells positive for CD99, WT1, vimentin and negative for pancytokeratin, desmin and myogenin, which is the pattern similar to cases previously reported. However, our case was also positive for BCL-2. Fluorescence in situ hybridization (FISH) was negative for EWSR1 and SS18 (SYT) rearrangements and positive for CIC gene rearrangement. On balance, if the following features are seen: (1) a small round blue cell tumor with histomorphology more atypical than that of Ewing sarcoma, (2) cytoplasmic CD99 staining, nuclear WT1 positivity, negative keratin, desmin and myogenin; and (3) EWSR1 rearrangement negative by FISH, then molecular testing for CIC-DUX4 sarcoma should be considered.

Increased Rate of ASCUS Diagnosis With Concomitant Request for High-Risk Human Papillomavirus Reflex Testing May Be Due to Cognitive Bias.

OBJECTIVES: To determine if concomitant high-risk human papillomavirus (HPV-HR) reflex testing may bias the cytologic interpretation of Papanicolaou (Pap) tests. METHODS: Percentage of atypical squamous cells of undetermined significance (ASCUS) and HPV-HR positivity was compared between Pap tests with HPV-HR cotesting and HPV-HR reflex testing for ASCUS, with subset analysis of cytopathologists' experience. RESULTS: ASCUS in the reflex group (41.5%) was significantly higher than the cotesting group (33.0%) (P = .02). There was no difference in HPV-HR positivity or ASCUS/squamous intraepithelial lesion (SIL) ratios between the two groups. The cytopathologists' experience inversely correlated with the proportion of ASCUS but did not explain the higher reflex group ASCUS. CONCLUSIONS: HPV-HR reflex testing may introduce bias in cytologic diagnosis, making it more likely that an ASCUS diagnosis is rendered. HPV-HR and ASCUS/SIL ratios were similar between the groups, so cytopathologist performance was not significantly affected. There was no effect of cytopathologists' experience.

Northern Italy in the American South: Assessing interobserver reliability within the Milan System for Reporting Salivary Gland Cytopathology.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has been proposed to standardize salivary gland fine-needle aspiration (FNA) diagnoses. This study assessed salivary gland FNA results and risk of malignancy (ROM) rates at the University of North Carolina as well as the interobserver reliability (IOR) of the atypia of undetermined significance (AUS) and salivary gland neoplasm of uncertain malignant potential (SUMP) categories. METHODS: The electronic medical record was searched for FNA cases from 2010 to 2017 with subsequent surgical resections. Histologic diagnosis was used for gold-standard comparison. The original cytologic results were then converted into MSRSGC categories (nondiagnostic, nonneoplastic, AUS, benign neoplasm, SUMP, suspicious, and malignant). For the assessment of IOR, 23 cases were selected with enrichment for cases diagnosed as AUS (n = 11) or SUMP (n = 9). Six boarded cytopathologists and 1 cytopathology fellow assessed representative slides and provided an MSRSGC diagnosis for each case. Fleiss' κ coefficients were calculated to determine IOR. RESULTS: The ROM was 33% for both AUS and SUMP cases; however, the risk of neoplasia was 56% for AUS cases and 100% for SUMP cases. Fleiss' κ for the AUS category was 0.217 (P < .05), and Fleiss' κ for the SUMP category was 0.024 (P = .74). CONCLUSIONS: In this study assessing the IOR of MSRSGC categories, fair agreement and slight agreement were found for the AUS and SUMP categories, respectively. Observers preferentially used the AUS or benign neoplasm category for SUMP cases, perhaps because of unfamiliarity with SUMP as a diagnostic option. The initial adoption of a new reporting system will require a quality assessment to ensure that the system is reliable and useful for clinicians. Cancer Cytopathol 2018;126:390-6. © 2018 American Cancer Society.

Intraosseous Rosai-Dorfman disease diagnosed by touch imprint cytology evaluation: A case series.

Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease (RDD) is a rare benign disorder that primarily affects the lymph nodes. Localized lymphadenopathy is the most common clinical manifestation of this disorder. However, RDD has been described in several extra-nodal sites including the head and neck region, soft tissue, skin, upper respiratory tract, gastro-intestinal tract and central nervous system (CNS). Involvement of the bone is considered very rare, occurring in less than 10% patients. RDD is one of the histiocytoses and the differential diagnosis includes entities such as Langerhans cell histiocytosis and Erdheim-Chester disease. In the rare intraosseous variant, the clinical and radiologic differential diagnosis is broader and includes neoplasms such as osteosarcoma and Ewing sarcoma. In this report, we describe three cases of extra-nodal, intraosseous RDD where touch imprint cytology played a crucial role in diagnosis. Two of the cases initially presented with involvement of the head and neck region and later developed intraosseous disease; while the third patient presented with primary bone involvement. The diagnosis was established by core biopsy with touch imprints of the bone lesions. The cytologic samples showed numerous histiocytes, often with neutrophils within their cytoplasm (emperipolesis) in addition to lymphocytes and plasma cells. The diagnosis of RDD was confirmed with appropriate immunohistochemical stains. Our account of these three cases of intraosseous Rosai-Dorfman disease highlights the role of cytology in the diagnosis of this rare entity.

Angiomatoid fibrous histiocytoma: novel MR imaging findings.

OBJECTIVE: To describe novel MR imaging features, and clinical characteristics of soft tissue angiomatoid fibrous histiocytoma (AFH) at presentation, local recurrence, and metastases. MATERIALS AND METHODS: We described the MRI findings of six cases of histologically proven AFH. Pathologic findings, clinical presentation, and outcome were reviewed. RESULTS: Lesions were primarily cystic. At initial presentation, tumors were surrounded by low signal intensity fibrous pseudocapsule. High signal intensity consistent with the lymphoplasmacytic infiltrate was seen in T2-weighted and post-contrast images as a rim over the hypointense pseudocapsule (double rim sign). High signal intensity infiltrating tumoral cords extended into adjacent tissues, through pseudocapsular defects on T2-weighted and post-contrast images. The cystic component and tumor cell nodularity were demonstrated at post-contrast images. Clinically, lesions were often thought to be benign, underwent marginal resection, developed local recurrence, and one developed second recurrence consisting of metastases. Recurrent tumors appeared as multiple masses, misinterpreted as post-surgical changes. An intramuscular recurrence demonstrated double rim and infiltrating margin. CONCLUSIONS: A predominantly well-circumscribed, primarily cystic mass with double-rim and marginal infiltration on MRI suggests the possibility of AFH, in particular in child or young adult. Inclusion of these novel observations in AFH differential diagnosis may have a significant impact on treatment and prevention of recurrence.

FNA smears as a potential source of DNA for targeted next-generation sequencing of lung adenocarcinomas.

BACKGROUND: Diff-Quik-stained fine-needle aspiration (FNA) smears and touch preparations from biopsies represent alternative specimens for molecular testing when cell block or biopsy material is insufficient. This study describes the use of these samples for targeted next-generation sequencing (NGS) of primary and metastatic lung adenocarcinoma and reports the DNA quality and success rates of FNA smears versus other specimens from 1 year of clinical use. METHODS: A validation set of 10 slides from 9 patients with prior clinical epidermal growth factor receptor (EGFR) Sanger sequencing and KRAS pyrosequencing (5 KRAS-positive/EGFR-negative and 4 KRAS-negative/EGFR-negative) underwent DNA extraction, quality assessment, and targeted NGS. Subsequently, lung adenocarcinoma specimens submitted for NGS solid tumor mutation panel testing in 1 calendar year (60 biopsies, 57 resections, 33 FNA cell blocks, 12 FNA smears, and 10 body fluid cell blocks) were reviewed for specimen adequacy, sequencing success, and DNA quality. RESULTS: All 10 validation samples met the DNA quality threshold (delta Ct threshold < 8; range, -2.2 to 4.9) and yielded 0.5 to 22 µg of DNA. The KRAS and EGFR mutation status from FNA smears according to NGS was concordant with previous clinical testing for all 10 samples. In the 1-year review, FNA smears were 100% successful, and this suggested a performance equivalent to or better than the performance of established specimen types, including FNA cell blocks. DNA quality according to ΔCt was significantly better with FNA smears versus biopsies, resections, and FNA cell blocks. CONCLUSIONS: FNA smears of lung adenocarcinomas are high-quality alternative specimens for a targeted NGS panel with a high success rate in clinical practice. Cancer Cytopathol 2016;124:406-14. © 2016 American Cancer Society.

Doing more with less: New markers for sarcoma diagnosis and their applicability to cytology specimens.

Sarcomas are a rare and extremely diverse set of neoplasms that are often a challenge to diagnose for pathologists. For a number of reasons, primary diagnosis of soft tissue neoplasms is increasingly being performed on small biopsy specimens including fine needle aspiration (FNA) and core needle biopsy (CNB). In the last several years, there has been a significant increase in our understanding of the molecular pathogenesis of this group of tumors. New insights into the genetic mechanisms of tumor formation have been exploited to create a new generation of diagnostic markers that are accessible to most laboratories. This review describes a number of new ancillary markers, and how they can facilitate accurate diagnosis of soft tissue neoplasms on FNA/CNB.