Identification of Glandular (Acinar)/Tubule Formation in Invasive Carcinoma of the Breast: A Study to Determine Concordance Using the World Health Organization Definition.

CONTEXT.­: The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS. OBJECTIVE.­: To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. DESIGN.­: A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule. RESULTS.­: Among 35 pathologists, the κ statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314-0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathologists included glands with complex architecture, mucinous carcinoma, and the "inverted tubule" pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule. CONCLUSIONS.­: We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules.

Dedifferentiated liposarcoma with heterologous rhabdomyosarcomatous differentiation in the bone marrow.

We present a case of advanced well-differentiated liposarcoma transforming to dedifferentiated liposarcoma in the bone marrow.Our patient presented with 5 weeks of worsening flank pain. He was found to have profound leukocytosis, thrombocytopenia, and normocytic anemia. Imaging showed a dominant retrocaval mass concerning for viable disease. Bone marrow biopsy revealed dedifferentiated liposarcoma with heterologous rhabdomyosarcomatous differentiation. He underwent 3 cycles of eribulin and subsequently developed complications of his increasingly aggressive liposarcoma. He was transitioned to hospice care and died 3 months after initial bone marrow biopsy. While exceedingly rare, it is possible for liposarcoma to metastasize to the bone marrow and cause rapid progression to death. In patients with high-grade liposarcoma, new cytopenia, leukocytosis, elevated granulocyte colony stimulating factor, and/or leukoerythroblasosis on peripheral smear should prompt bone marrow biopsy for early detection of this rare disease entity.

Follicular dendritic cell sarcoma: Cytomorphologic features and diagnostic challenges.

Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm, which primarily arises in lymph nodes with occasional cases occurring in extranodal locations. The diagnosis is often challenging particularly on cytology fine needle aspiration due to overlapping morphologic and immunohistochemical features. We present a case of FDCS diagnosed in an otherwise asymptomatic 33-year old male. The aim of our case report is to highlight the key cytomorphologic features and discuss various differential diagnoses of this unusual entity.

Application of the Milan System for Reporting Salivary Gland Cytopathology: Experience of an academic institution in a tertiary academic medical center.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) represents a standardized reporting system for salivary gland lesions. The recent literature has demonstrated a wide range of data regarding range of malignancy (ROM) and interobserver variability. The objective of the current study was to evaluate the reproducibility and interobserver agreement of MSRSGC, and establish the ROM in a unique patient population residing within a designated Health Professional Shortage Area. METHODS: A total of 380 salivary gland fine-needle aspiration cases were obtained over a 3-year period. Corresponding cytology reports and slides were reviewed in a blinded fashion by a panel of cytopathologists and recategorized using MSRSGC. ROM was calculated by cytohistologic correlation in 176 cases. Agreement between review of reports and slides and interobserver reliability were determined using kappa statistics. RESULTS: The ROMs per MSRSGC category based on review of reports and slides were as follows: 4% and 0%, respectively, for nonneoplastic; 22% and 0%, respectively, for nondiagnostic; 42.9% and 48%, respectively, for atypia of undetermined significance; 1.6% and 1.9%, respectively, for benign-neoplastic; 17.9% and 15.6%, respectively, for salivary gland neoplasm of uncertain malignant potential; 81.8% and 71.4%, respectively, for suspicious for malignancy; and 100% and 90.5%, respectively, for malignant. There was a 59.2% overall agreement between review of reports and slides with regard to recategorizing salivary gland lesions (kappa, 0.51). The interobserver reliability demonstrated a 64.6% agreement (weighted kappa, 0.59). CONCLUSIONS: The ROMs at the study institution appeared comparable to those in the published literature. There was moderate overall agreement among cytopathologists and low interobserver agreement with regard to the indeterminate categories. Image-guided fine-needle aspiration specimens; rapid onsite adequacy; and integration of clinical, imaging, and ancillary studies can improve diagnostic accuracy among indeterminate lesions.

The predictive value of positive and suspicious urine cytology: Are they different?

BACKGROUND: Urine cytology evaluation is an effective test in the detection of high-grade urothelial carcinoma (HGUC). While the guideline distinguishes the 2 categories: "positive for HGUC" (PHGUC) and "suspicious for HGUC" (SHGUC), the association between these categories with their subsequent follow-up biopsies remains unclear. This study aims to determine and compare the positive predictive value (PPV) of the specimens in PHGUC and SHGUC categories with their respective histologic diagnoses. METHODS: During the period of 03/01/2008 to 07/31/2018, urine cytology cases diagnosed as PHGUC and SHGUC with subsequent bladder biopsy within 12 months were retrieved. All cases were correlated with first biopsy obtained during 12 months of cytology specimen. Biopsy result with HGUC, carcinoma in situ, or non-urothelial carcinoma diagnoses were considered as concordance. RESULTS: 378 cases (229 SHGUC and 149 PHGUC) were identified from 263 patients. For the 229 SHGUC cases, the PPV was 72% (n = 166) and for the 149 PHGUC cases, the PPV was 85% (n = 127). While both categories have high PPV, they are statistically significant (p < 0.0001). Additionally, 33 cases were found to have low-grade urothelial carcinoma (LGUC), constituting a portion of discordant results. CONCLUSION: PHGUC and SHGUC categories are both associated with a high risk of malignancy, however, there is a statistically significant difference between them in our study, supporting the PSRUC guidelines of two separate categories. In instances when urine cytology is discordant with biopsy results, further investigation and clinical follow up is warranted. LGUC appears to remain a common pitfall especially in the suspicious category.

Low-grade squamous intraepithelial lesion, cannot rule out high-grade lesion: Diagnosis, histological outcomes and human papillomavirus results.

BACKGROUND: The 2014 Bethesda System for Reporting Cervical Cytology classifies squamous intraepithelial lesions (SILs) of cervix into two main categories: low-grade SIL (LSIL) and high-grade SIL (HSIL). In some clinical practices, the LSIL cannot rule out high-grade lesion (LROH) interpretive category is used in cases with LSIL and findings that may raise the possibility of HSIL. Our purpose is to assess follow-up histopathology and high-risk human papillomavirus (hrHPV) results in patients with LROH, in comparison with LSIL, atypical squamous cells, cannot rule out HSIL (ASC-H), and HSIL in our institution. DESIGN: Cervical Papanicolaou tests with LROH, LSIL, ASC-H and HSIL interpretation, surgical follow-up, and hrHPV status were retrieved from the computer database from May 2014 to December 2016. RESULTS: Of 109 963 total Papanicolaou tests, LROH comprised 0.3%, LSIL 3.1%, ASC-H 0.2% and HSIL 0.4%. Only 3272 cases with surgical diagnoses were included in the study. The most common histological outcome for ASC-H was cervical intraepithelial neoplasia (CIN)2/3 (32.6%); LSIL was CIN 1 (45.7%); LROH was CIN 1 (46.7%) and HSIL was CIN 2/3 (64.4%). For LROH and LSIL, 31.1% and 7.5% respectively, had CIN 2/3. Approximately 79% of cases were hrHPV positive. Of LROH cases with surgical follow-up, 86.9% tested hrHPV positive, accounting for the second most common positive group after HSIL (92.6%). CONCLUSION: In our study cohort, LROH interpretation is associated with a higher number of CIN 2 or higher lesions on follow-up compared to patients with LSIL (P < 0.0001), and is associated with a significant percentage of positive other hrHPV, supporting LROH as a useful diagnostic category that triggers appropriate follow-up in affected women.

Differential expression of various clones of estrogen receptor in cell block preparation of lung adenocarcinoma.

BACKGROUND: Women treated for breast cancer are at increased risk of developing pulmonary nodules which could represent new primary lung carcinomas or metastatic breast carcinoma. The FNA biopsy is frequently the first diagnostic choice in determining the primary site of the tumor. Estrogen receptor (ER) positivity in diagnostic tissue is generally used to favor breast over lung primary. However, the recent studies have shown a wide range of ER antibody cross reactivity with lung adenocarcinoma. We studied the frequency of ER expression in cytology samples of lung adenocarcinoma using antibodies to three different ER clones. METHODS: Cytology cell block preparations, including 22 lung FNAs and 19 malignant pleural effusions (PE) from 41 patients, with clinically documented primary lung adenocarcinomas were selected for this study. All cases were stained with monoclonal antibodies to ER clones 6F11 and 1D5. Twenty nine cases with remaining available material (15 FNA and 14 PE) were stained with a third antibody to ER clone SP1. The extent of ER nuclear staining was scored as 3+ (50%-100% of tumor cells), 2+ (11%-49%), and 1+ (≤10%). RESULTS: Positivity for ER-6F11 clone was present in 4 of 22 lung FNAs (18.2%, 2+ staining). Two of the four 6F11 positive FNAs also co-expressed ER-1D5 (9.1%, 2+ staining). No immunoreactivity was observed for ER clones 6F11 and 1D5 in all 19 malignant PEs. In addition, none of the remaining 15 FNAs and 14 PEs showed immunoreactivity for ER-SP1 clone. CONCLUSIONS: A small subset of pulmonary adenocarcinomas shows immunoreactivity for ER clones 6F11 and 1D5 in FNA samples (18.2% and 9.1%, respectively). The absence of immunoreactivity for ER-SP1 clone indicates higher specificity of this clone in non-breast tissue. The differential diagnostic value of all ER clones in malignant PEs appears to be secure. Larger studies are necessary to validate this observation.

The Application of Molecular Diagnostics to Stained Cytology Smears.

Detection of mutational alterations is important for guiding treatment decisions of lung non-small-cell carcinomas and thyroid nodules with atypical cytologic findings. Inoperable lung tumors requiring further testing for staging and thyroid lesions often are diagnosed using only cytology material. Molecular diagnostic tests of these samples typically are performed on cell blocks; however, insufficient cellularity of cell blocks is a limitation for test performance. In addition, some of the fixatives used while preparing cell blocks often introduces artifacts for mutation detection. Here, we applied qClamp xenonucleic technology and quantitative RT-PCR to cells microdissected directly from stained cytology smears to detect common alterations including mutations and translocations in non-small-cell carcinomas and thyroid lesions. By using this approach, we achieved a 1% molecular alteration detection rate from as few as 50 cells. Ultrasensitive methods of molecular alteration detection similar to the one described here will be increasingly important for the evaluation of molecular alterations in clinical scenarios when only tissue samples that are small are available.

Hybrid Capture 2 human papillomavirus testing of fine needle aspiration cytology of head and neck squamous cell carcinomas.

BACKGROUND: Human papillomavirus (HPV) positive head and neck squamous cell carcinoma (HNSCC) accounts for 25% of HNSCCs and frequently presents with neck lymph node metastases. We investigated utilizing cytology needle rinse material for HPV DNA testing by Hybrid Capture 2 molecular testing (HC2) as an alternative to p16 immunohistochemistry. METHODS: Twenty-two cases of HNSCC presenting with neck lymph node metastasis were prospectively identified by assessment of Diff Quik stained cytology smears. An aliquot of the needle rinse material from the lymph node was analyzed for HPV status using standard HC2 protocol. P16 status was determined with immunohistochemistry on the cell block and/or surgically obtained tumor. RESULTS: The mean age of patients with p16 negative HNSCC was 7 years older than p16 positive disease (Table ). Primary tumor subsites were as follows: 17 oropharynx, 1 hypophayrnx, 3 larynx, and 1 oral cavity (Table ). All ten p16 negative patients had a history of smoking compared with 33% of p16 positive. Only 3 (25%) of p16 positive tumors demonstrated keratinization, whereas 90% of the p16 negative tumors keratinized (Fig. 1). Twelve of 22 HNSCC cases (55%) were p16 positive, of which 7 (58%) tested positive for HPV by HC2. Ten cases (45%) were negative for p16, all of which were negative for HPV by HC2 (Table ). CONCLUSION: Molecular testing for HPV using HC2 on needle rinse material of FNA of HNSCC is a useful method of determining HPV status in HNSCC.

Myxoid degeneration of appendix wall: An entity in search of identity: Report of two cases.

Myxoid degeneration of the appendix wall without accompanying acute appendicitis (AA) is rare. We report two cases of myxoid degeneration of appendix associated with appendiceal adhesions. Both the cases showed marked splitting and disruption of smooth muscle fibers of muscularis propria by abundant myxoid ground substance and dispersed degenerated hypereosinophilic myofibers with pyknotic nuclei. Scattered degenerated myocytes with vacuolated cytoplasm were also identified. Focal serosal fibrosis was observed in both cases. We reviewed other pathologic processes that involve the appendix such as fibrous obliteration, AA, and appendiceal mucinous neoplasm (AMN) and conclude that the constellations of pathologic findings described herein are unique. Nonneoplastic dissecting myxoid degeneration of the appendix muscularis propria has not been reported in the pathology literature to date. The pathologic nature of appendiceal mucinous stromal change remains unclear; however, we hypothesize that the lesion occurs as a consequence of traction related injury to the appendix.

Clinical dilemma of positive histologic chorioamnionitis in term newborn.

BACKGROUND: Although histologic chorioamnionitis (HCA) is known to be associated with poor outcomes in preterm infants, its clinical significance among term infants is not clearly known. OBJECTIVES: To investigate the utility of HCA in determining early onset clinical sepsis (EOCS) among term newborns. METHODS: The incidence of HCA and EOCS in term infants born during 2008-2009 was evaluated in a single center retrospective study (n = 3417). The predictive value of HCA for determining EOCS in term infants admitted to the neonatal intensive care unit (NICU) for suspected sepsis (n = 388) was quantified. Outcome of otherwise healthy term infants in the nursery with HCA was also investigated. RESULTS: Overall, 11% of term infants with HCA also had EOCS. HCA was associated with increased risk for EOCS (OR 2.6, 95% confidence interval 1.6-4.2, P < 0.001) among term infants admitted to the NICU for suspected sepsis. No cases of EOCS were found among otherwise well-appearing infants in the nursery with HCA. Multiple logistic regression analysis indicated that addition of HCA does not increase the power of a model combining C-reactive protein (CRP) and immature to total neutrophil ratio in determining EOCS. CONCLUSION: Although HCA in term infants is associated with EOCS, it did not improve the ability of CRP and immature to total neutrophil ratio to predict EOCS. Routine placental examination may not contribute to the diagnosis of EOCS in term infants.

Radiologic-pathologic findings of primary osseous adamantinoma with unusual metastasis to the posterior cul-de-sac in pregnancy.

Adamantinoma is a rare primary bone malignancy with a predilection for the tibial cortex. Metastases have been reported to the long bones, lung, pleura and spine. We present a 26-year-old pregnant woman with metastatic disease to the posterior cul-de-sac, lungs, liver and retroperitoneum, which collectively have not been previously reported in a single patient to our knowledge.