Fine Needle Aspiration Cytology of Metastatic Plasmacytoid Urothelial Carcinoma- Report of Four Cases Including a Case of Mixed Plasmacytoid and Micropapillary Morphology

Objectives: The aim of this study was to report a small series of fine-needle aspiration (FNA) cytology of the plasmacytoid variant of urothelial carcinoma (PVUC). Study Design: A computerized search of our laboratory information system was performed for the 5-year period between January 2008 and January 2013 to identify all FNA cases in which the corresponding surgical pathology cases were diagnosed as PVUC. Results: The 4 cases identified were from 2 men (aged 56 and 64 years) and 2 women (aged 72 and 46 years). The FNA smears demonstrated low-to-moderate cellularity and consisted predominantly of single and dyshesive, medium-sized tumor cells with eccentrically located nuclei and a moderate-to-abundant dense cytoplasm. The nuclei were oval with slightly irregular nuclear membranes and contained coarse granular chromatin with inconspicuous or small nucleoli. There was moderate nuclear variation in size. The nuclear-to-cytoplasmic ratio ranged from <1 to 3. Binucleation, cytoplasmic vacuoles, and perinuclear hof were occasionally seen. Conclusions: FNA cytology of PVUC shares features with plasma cell neoplasms, lobular carcinoma of the breast, and signet ring cell carcinoma of the stomach. Being aware of the patient's clinical history and the potential diagnostic pitfall of this rare variant of urothelial carcinoma is important for an accurate diagnosis on FNA biopsy

Variant morphology in upper urinary tract urothelial carcinoma: a fourteen-year case series of biopsy and resection specimens

Upper urinary tract urothelial carcinoma exhibiting variant morphology, especially in higher-grade tumors, is a recognized phenomenon but has not been comparatively studied in biopsy versus resection material. We studied the morphologic patterns and clinicopathological features, and provide a comparison between biopsy and resection specimens. Consultation cases were evaluated separately to investigate for possible consultation bias. A total of 383 in-house cases from 352 patients including 314 resection specimens and 69 biopsies from 2001–2014 were reviewed from a single institution. Histologic type, tumor grade, invasion, pathologic stage, nodal status, metastasis, and the presence and type of variant morphology for each case were evaluated. Variant morphology was identified in 5 biopsy specimens (7.2%) and 42 resection specimens (13.4%). The most common variant morphologic pattern was squamous differentiation (16 cases, 4.5%) followed by an inverted growth pattern (8 cases, 2.2%). The presence of variant morphology in resection specimens had a significant association with higher tumor grade, higher pT stage, and non-papillary configuration. Out of 69 patients with biopsies, 31 had a subsequent resection. In comparison, 181 consultation cases from 168 patients showed variant morphology in six biopsies (7.1%) and twenty-seven resections (28.1%). In conclusion, the frequency of recognizing variant morphology in biopsies is about one-half of that in resections. The inclusion of consultation cases can inflate the incidence of variant morphology. As a result, the frequency of variant morphology in our in-house cases is lower than the percentage reported in the literature, most likely secondary to a consultation bias

The application of the Johns Hopkins Hospital Template on urine cytology

Background To evaluate the utility of the Johns Hopkins Hospital (JHH) template in detection of high-grade urothelial carcinoma (HGUC). Methods A computerized search of our laboratory information system was performed for all urine cytology cases from 2009 to 2011 processed by the SurePath™. We included only cases with correlating surgical pathology within 6 months after the urinary samples were obtained. The original cytologic diagnoses were reclassified according to the JHH template, and these cytolog ic diagnoses were then correlated with the follow-up surgical pathology diagnoses. Results A total of 273 urine samples with histopathologic follow-up were identified. The reclassified cytologic diagnoses included negative for urothelial atypia or malignancy (NUAM) 110; atypical urothelial cells of undetermined significance (AUC-US) 83; atypical urothelial cells, cannot exclude high-grade urothelial carcinoma (AUC-H) 49; HGUC 29; and low-grade urothelial carcinoma (LGUC) 2. More than one-half of patients (58%) who had biopsy-confirmed high-grade urothelial lesions had a preceding cytologic diagnosis of AUC-H or HGUC. AUC-H and HGUC are associated with high-grade urothelial lesions in 80% and 90% of the cases and show statistical significance when compared with AUC-US or NUAM (P < 0.05). Conclusion The JHH template is useful and effective in identifying patients with high-grade urothelial lesions who need to undergo cystoscopy. Diagn. Cytopathol. 2015;43:593–597. © 2015 Wiley Periodicals, Inc

Immunohistochemical characteristics of Renomedullary interstitial cell tumor: a study of 41 tumors with emphasis on differential diagnosis of mesenchymal neoplasms

Renomedullary interstitial cell tumors (RMICT) are almost always incidentally identified either at autopsy or resection of the kidney for other reasons. However, rare cases have been reported which are large, resulting in a clinical mass. The immunohistochemical phenotype of usual, incidental RMICT using modern soft tissue tumor markers in is largely unknown, however, providing little information to aid in classification of larger or atypical tumors. We retrieved 41 RMICTs from 36 patients, and studied pathologic characteristics including morphology, immunohistochemistry (S100, keratin AE1/AE3, smooth muscle actin, desmin, estrogen and progesterone receptors, calponin, CD34, CD35), and histochemical staining. Data collected included age, gender, tumor size, laterality, and indication for kidney examination. RMICTs (n = 41) were identified in 23 men and 13 women, with mean age 57 years (range 24–83), tumor sizes ranged from <1 to 13 mm (median 4 mm). Kidneys were resected for 32 tumors, 1 chronic pyelonephritis, 1 trauma, and 2 autopsies. All (41, 100%) had entrapped renal tubules, 5 (12%) of which included cystic or dilated tubules. Most (35, 85%) had collagenous fibers, all of which were negative for Congo red. RMICT demonstrates a largely negative immunohistochemical phenotype with weak to moderate labeling for smooth muscle actin and calponin that is substantially less than myofibroblastic lesions. Positive staining for estrogen and progesterone receptor is common (61%), which could overlap with mixed epithelial and stromal tumor and other entities; however, staining is typically weak. CD34 is usually negative, with occasional weak labeling, in contrast to solitary fibrous tumor

Morphologic Spectrum of Renal Cell Carcinoma, Unclassified: An Analysis of 136 Cases

Aims Renal cell carcinoma, unclassified (RCCU) is a category that includes a morphologically and biologically heterogeneous group of tumors that are unable to be diagnosed as other well-defined entities. We aim to describe the morphologic findings of tumors within this category and to determine the most frequent morphologic features leading to classification difficulty. Methods and results One hundred and thirty-six cases of RCCU were examined. Patients ranged in age from 23 to 87 years. Seventy-seven patients were men and 59 were women. International Society of Urological Pathology (ISUP) grade was most commonly 3 (n=66), followed by 2 (n=42) and 4 (n=28). Tumor size ranged from 0.6 cm to 24.9 cm. The AJCC pathologic T categories included pT1a (n=50), pT1b (n=14), pT2a (n=7), pT2b (n=4), pT3a (n=50), and pT4 (n=9). Forty-four cases included lymph node(s), of which 41% (n=18) had metastases. Tumors were assessed for a variety of histologic features and assigned to the following morphologic groups: predominantly oncocytoma/chromophobe RCC-like; clear cell RCC-like; papillary RCC-like; collecting duct-like; and pure sarcomatoid differentiation. The majority of the oncocytoma/chromophobe and clear cell RCC-like phenotypes were low stage (pT1 or pT2). The papillary RCC-like, collecting duct-like, and pure sarcomatoid phenotypes were mostly high stage (pT3 or pT4). Conclusions RCCU is a term that encompasses tumors with a variety of morphologic features and a wide biologic spectrum. The most common source of diagnostic difficulty was tumors composed of predominantly eosinophilic cells

DOG1 immunohistochemical staining of testicular biopsies is a reliable tool for objective assessment of infertility

Testicular biopsy may be a component of the work-up of male infertility. However, no reliable diagnostic tools are available for objective quantitative assessment of spermatogenic cells. It is well known that MAGE-A4 is selectively expressed in spermatogonia and our group has previously demonstrated that DOG1 differentially stains germ cells. Therefore, we performed DOG1 and a double stain cocktail (DOG1 and 57b murine monoclonal anti-MAGE-A4) immunohistochemical stains on 40 testicular infertility biopsies (10 each with active spermatogenesis, Sertoli cell-only, hypospermatogenesis, and maturation arrest), 25 benign seminiferous tubules from radical orchiectomies, and 5 spermatocytic tumors (ST). In biopsies/resections with active spermatogenesis, DOG1 stained spermatocytes and spermatids and was absent in spermatogonia, while MAGE-A4 stained spermatogonia and primary spermatocytes (weak). In hypospermatogenesis, DOG1 highlighted decreased spermatocytes/spermatids and MAGE-A4 highlighted decreased spermatogonia. DOG1 staining confirmed decreased to absent spermatocytes in maturation arrest and MAGE-A4 staining established the presence of preserved spermatogonia in all cases. All STs were negative for DOG1 and positive for MAGE-A4, while all Sertoli cell-only cases were negative for DOG1 and the double stain cocktail. In conclusion, we confirmed that DOG1 is expressed in spermatocytes and spermatids and MAGE-A4 highlights primarily spermatogonia. Usage of these stains facilitates confirmation of maturation arrest, assessment of the percentage of testis involvement in hypospermatogenesis and identification of mixed patterns. Finally, this study supports that the differentiation of STs is more closely related to spermatogonia than the more mature spermatocytes

Characterization of pancreatic lesions from MT-tgfα, Ela-myc and MT-tgfα/Ela-myc single and double transgenic mice

In order to identify good animal models for investigating therapeutic and preventive strategies for pancreatic cancer, we analyzed pancreatic lesions from several transgenic models and made a series of novel findings. Female MT-tgfα mice of the MT100 line developed pancreatic proliferation, acinar-ductal metaplasia, multilocular cystic neoplasms, ductal adenocarcinomas and prominent fibrosis, while the lesions in males were less severe. MT-tgfα-ES transgenic lines of both sexes developed slowly progressing lesions that were similar to what was seen in MT100 males. In both MT100 and MT-tgfα-ES lines, TGFα transgene was expressed mainly in proliferating ductal cells. Ela-myc transgenic mice with a mixed C57BL/6, SJL and FVB genetic background developed pancreatic tumors at 2–7 months of age, and half of the tumors were ductal adenocarcinomas, similar to what was reported originally by Sandgren et al [1]. However, in 20% of the mice, the tumors metastasized to the liver. MT100/Ela-myc and MT-tgfα-ES/Ela-myc double transgenic mice developed not only acinar carcinomas and mixed carcinomas as previously reported but also various ductal-originated lesions, including multilocular cystic neoplasms and ductal adenocarcinomas. The double transgenic tumors were more malignant and metastasized to the liver at a higher frequency (33%) compared with the Ela-myc tumors. Sequencing of the coding region of p16ink4, k-ras and Rb cDNA in small numbers of pancreatic tumors did not identify mutations. The short latency for tumor development, the variety of tumor morphology and the liver metastases seen in Ela-myc and MT-tgfα/Ela-myc mice make these animals good models for investigating new therapeutic and preventive strategies for pancreatic cancer

Renal Cell Carcinoma with Angioleiomyoma-Like Stroma and Clear Cell Papillary Renal Cell Carcinoma: Exploring SDHB Protein Immunohistochemistry and the Relationship to Tuberous Sclerosis Complex

Renal cell carcinoma (RCC) with angioleiomyoma-like stroma appears to be molecularly distinct from clear cell RCC; however, its relationship to clear cell papillary RCC remains debated. Recent studies have found that similar tumors sometimes occur in patients with tuberous sclerosis complex (TSC), of which one study found unexpectedly negative succinate dehydrogenase (SDH) B immunostaining. We evaluated immunohistochemistry for SDHB in 12 apparently sporadic RCCs with angioleiomyoma-like stroma and correlated with clinical information for stigmata of TSC. Tumors were compared to a group of 16 clear cell papillary RCCs and 6 unclassified tumors with prominent stroma. With exception of 1 unclassified tumor, all exhibited at least focal cytoplasmic staining for SDHB protein, often requiring high magnification and better appreciated with increased antibody concentration. Detailed history information was available for 9/12 patients with smooth muscle-rich tumors, revealing no stigmata of undiagnosed TSC. Electron microscopy performed on 1 of these tumors revealed mitochondria to be very sparse, potentially accounting for the weak immunohistochemical labeling for SDHB protein. Weak SDHB immunostaining may represent another shared feature of RCC with angioleiomyoma-like stroma and clear cell papillary RCC, likely due to sparse mitochondria, strengthening the possible relationship of these entities. Although smooth muscle-rich tumors have been recently reported in patients with TSC, absence of staining in tumors with this pattern may not be specific for TSC. In tumors with pale or clear cytoplasm, immunohistochemical staining for SDHB should be interpreted with caution as evidence of abnormality in the SDH pathway

High prevalence of HPV in non-cervical sites of women with abnormal cervical cytology.

BACKGROUND: Human papillomaviruses (HPV) are causally associated with ano-genital and a subset of head and neck cancers. Rising incidence of HPV+ anal cancers and head and neck cancers have now been demonstrated in the developed world over the last decade. The majority of published data on HPV prevalence at the anal and oro-pharyngeal sites are from studies of higher-risk populations. There is a paucity of data on the prevalence of HPV at non-cervical sites in lower risk, non-HIV+ women and this study was designed to provide initial pilot data on a population of women recalled for colposcopy as part of the UK cervical screening programme. METHODS: 100 non-HIV+ women with abnormal cervical cytology, attending clinic for colposcopic examination were recruited. Swabs from the oro-pharyngeal, anal and cervical sites were taken and DNA extracted. HPV detection and genotyping were performed using a standardised, commercially available PCR-line blot assay, which is used to genotype 37 HPV subtypes known to infect the ano-genital and oro-pharyngeal areas. Strict sampling and laboratory precautions were taken to prevent cross-contamination. RESULTS: There was a very high prevalence of HPV infection at all three sites: 96.0%, 91.4% and 92.4% at the cervix, anus and oro-pharynx, respectively. Multiple HPV subtype infections were dominant at all 3 mucosal sites. At least one or more HR genotype was present at both the cervix/anus in 39/52 (75.0%) patients; both the cervix/oro-pharynx in 48/56 (85.7%) patients; and both the anus/oro-pharynx in 39/52 (75.0%) patients. HPV 16 infection was highly dominant across all mucosal sites, with over a 2-fold increase over the next most prevalent subtype (HPV 31). CONCLUSIONS: Women with abnormal smears have widespread infection with high-risk HPV at the cervical, anal and oro-pharyngeal mucosal sites and may represent a higher risk population for HPV disease in the future.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Preservation of Truncal Genomic Alterations in Clear Cell and Papillary Renal Cell Carcinomas with Sarcomatoid Features: An Intra- and Intertumoral, Multifocal Fluorescence in Situ Hybridization Analysis Reveals Limited Genetic Heterogeneity

Understanding tumor genomic heterogeneity may offer vital information in an age of targeted therapy for renal cell carcinoma. We sought to investigate hallmark truncal chromosomal alterations between conventional, sarcomatoid, and matched metastatic tumor foci in clear cell and papillary renal cell carcinomas. A retrospective review identified 58 cases including clear cell (CCRCC) and papillary renal cell carcinomas (PRCC). All cases contained sarcomatoid transformation. Additionally, 10 of 58 patients had matched metastatic disease available for analysis. Three separate foci of conventional and sarcomatoid morphologies were analyzed in each tumor using dual color interphase fluorescence in situ hybridization. In the CCRCC cohort, hallmark chromosome 3p deletion was identified in 71% of cases (37/52). Complete concordance of chromosomal status between intratumoral foci in sarcomatoid and conventional foci was 89% and 86%, respectively. Overall chromosome 3p status between matched conventional and sarcomatoid morphologies was identified in 98% of cases (51/52). Hallmark 3p deletion was present in 91% of CCRCC metastatic samples (10/11) and was concordant with the matched primary CCRCC tumor in 91% (10/11). In the PRCC cohort, trisomy 7 and 17 was identified in all six cases (6/6). Complete concordance between intratumoral foci of trisomy 7 and 17 was 83% (5/6). Trisomy 7 and 17 were identified in all metastatic PRCC samples with 100% concordance with the matched primary tumor. These data show the relative preservation of truncal chromosomal abnormalities between conventional and sarcomatoid morphologic as well as matched metastatic settings