Thyroid-Like Low-Grade Nasopharyngeal Papillary Adenocarcinoma

Abstract Objectives Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TLLGNPPA) is a relatively rare nasopharyngeal tumor. We performed morphological characterization, immunohistochemical profiling, and investigated gene mutations. We also provide clinical follow-up data and brief review of the literature. Methods Immunohistochemistry was used to evaluate the expression of TTF-1, CK19, CK7, EMA, TG, Pax-8, CK5/6, S100, and Ki-67. Additionally, in situ hybridization was utilized to identify the presence of EBV. We investigated mutations in hot-spot exons of KRAS/NRAS/BRAF to rule out common mutations seen in thyroid tumors. Results Histopathologic examination of four cases identified tumors that were mainly occupied by papillary architectures. One case had a predominantly glandular structure. The tumors expressed TTF-1 and CK19, while TG and Pax-8 were negative. S100 was moderately expressed focally in three cases. Conclusions While TLLGNPPA displays a morphological resemblance to papillary thyroid carcinoma (PTC), it is vital to differentiate nasopharyngeal metastasis from PTC for appropriate treatment.

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Intra-Cystic (In Situ) Mucoepidermoid Carcinoma: A Clinico-Pathological Study of 14 Cases

Journal of Clinical Medicine ◽

10.3390/jcm9041157 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1157

Author(s):

Saverio Capodiferro ◽

Giuseppe Ingravallo ◽

Luisa Limongelli ◽

Mauro Mastropasqua ◽

Angela Tempesta ◽

...

Keyword(s):

Alcian Blue ◽

Tumor Invasion ◽

Conservative Surgery ◽

Low Grade ◽

Mucin Production ◽

Cystic Component ◽

Early Growth Phase ◽

Hematoxylin Eosin

Aims: To report on the clinico-pathological features of a series of 14 intra-oral mucoepidermoid carcinomas showing exclusive intra-cystic growth. Materials and methods: All mucoepidermoid carcinomas diagnosed in the period 1990–2012 were retrieved; the original histological preparations were reviewed to confirm the diagnosis and from selected cases, showing exclusive intra-cystic neoplastic components, additional sections were cut at three subsequent 200 m intervals and stained with Hematoxylin–Eosin, PAS, Mucicarmine and Alcian Blue, to possibly identify tumor invasion of the adjacent tissues, which could have been overlooked in the original histological preparations. Additionally, pertinent findings collected from the clinical charts and follow-up data were analyzed. Results: We identified 14 intraoral mucoepidermoid carcinomas treated by conservative surgery and with a minimum follow up of five years. The neoplasms were located in the hard palate (nine cases), the soft palate (two), the cheek (two) and the retromolar trigone (one). In all instances, histological examination revealed the presence of a single cystic space, containing clusters of columnar, intermediate, epidermoid, clear and mucous-producing cells, the latter exhibiting distinct intra-cytoplasmic mucin production, as confirmed by PAS, Mucicarmine and Alcian Blue stains. The cysts were entirely circumscribed by fibrous connective tissue, and no solid areas or infiltrating tumor cell clusters were detected. Conservative surgical resection was performed in all cases, and no recurrences or nodal metastases were observed during follow up. Conclusions: Mucoepidermoid carcinomas showing prominent (>20%) intra-cystic proliferation currently are considered low-grade tumors. In addition, we also unveil the possibility that mucoepidermoid carcinomas, at least in their early growth phase, may display an exclusive intra-cystic component and might be considered as in situ carcinomas, unable to infiltrate adjacent tissues and metastasize.

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Radionuclide Brain Scans in Convulsive Disorders?

PEDIATRICS ◽

10.1542/peds.49.5.787a ◽

1972 ◽

Vol 49 (5) ◽

pp. 787-788

Author(s):

Gerald S. Golden ◽

Gerald Erenberg

Keyword(s):

Arteriovenous Malformation ◽

Neurological Examination ◽

Does Urine Cytology Still have a Role?

Urologia Journal ◽

10.1177/039156030507200301 ◽

2005 ◽

Vol 72 (3) ◽

pp. 301-306

Author(s):

M. Ciaccia ◽

R. Bertoloni ◽

F. Pinto ◽

A. Calpista ◽

P.F. Bassi

Keyword(s):

Transitional Cell Carcinoma ◽

Cell Carcinoma ◽

Carcinoma In Situ ◽

Transitional Cell ◽

High Sensitivity ◽

Urine Cytology ◽

Low Grade ◽

New Methods

Urine cytology is a reliable and well known tool in the diagnosis and follow-up of patients with transitional cell carcinoma even if it has high sensitivity only in high grade tumors and carcinoma in situ. In order to improve sensitivity of this test in patients with low grade tumors, new methods such as cytometry, microsatellite assays, Immunocyt®, fuorescence in-situ hybridization and Thin-Prep monolayer have been developed. These new assays will be able to increase the cytology detection rate and to predict the outcome of transitional cell carcinoma.

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Subareolar Sclerosing Ductal Hyperplasia

International Journal of Surgical Pathology ◽

10.1177/1066896916677288 ◽

2016 ◽

Vol 25 (1) ◽

pp. 4-11 ◽

Cited By ~ 2

Author(s):

Esther Cheng ◽

Timothy M. D’Alfonso ◽

Maria Arafah ◽

Rebecca Marrero Rolon ◽

Paula S. Ginter ◽

...

Keyword(s):

Carcinoma In Situ ◽

Ductal Carcinoma ◽

Lobular Carcinoma ◽

Low Grade ◽

Solitary Lesion ◽

Ductal Hyperplasia ◽

Long Term Follow Up ◽

Initial Description

Subareolar sclerosing duct hyperplasia (SSDH) remains to be fully characterized nearly 20 years after initial description. Thirty-five SSDH cases diagnosed over a 16-year period (January 2000 to December 2015) were reviewed. All patients were female (mean age = 59 years, range = 18-80) who had presented with a unilateral solitary lesion (left 22, right 13) with a mean size of 1.3 cm (range = 0.4-3.0 cm), and showed florid and papillary epithelial hyperplasia with dense sclerosis without involvement of nipple or areolar epidermis. Significant lesions concurrent within SSDH included low-grade adenosquamous carcinoma (n = 1), ductal carcinoma in situ (DCIS; n = 1), lobular carcinoma in situ (LCIS; n = 1), and atypical ductal hyperplasia (ADH; n = 13). No case of SSDH recurred in a mean follow-up of 44 months (range = 6-189). Subsequent significant lesions occurred in 6 patients: DCIS (n = 3; ipsilateral 2, contralateral 1), ipsilateral ADH (n = 2), and ipsilateral atypical lobular hyperplasia (n = 1). Long-term follow-up for patients with SSDH is indicated as DCIS can occur subsequently in either breast.

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Characterization of molecular features of pediatric urothelial bladder carcinomas.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.345 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 345-345

Author(s):

Ana Collazo Lorduy ◽

Mireia Castillo-Martin ◽

Grace Hyun ◽

Nataliya Gladoun ◽

Carlos Cordon-Cardo

Keyword(s):

Bladder Cancer ◽

Mutational Analysis ◽

Pediatric Population ◽

Pcr Amplification ◽

Low Grade ◽

Pediatric Tumors ◽

Rare Entity ◽

Ki 67 ◽

Molecular Features

345 Background: Bladder cancer is a rare entity in the pediatric population making it difficult to define surveillance protocols and long term outcomes. Notably, most pediatric tumors are low grade and non-muscle invasive and do not recur. In order to determine the source of the different natural history between pediatric population and adults, we hypothesized that pediatric bladder cancer may potentially stem from different molecular pathways than its adult form. Our main objective was to study the molecular pathogenesis in this rare disease using immunohistochemical (IHC) and mutational analysis of the main known genes involved in bladder cancer. Methods: Paraffin-embedded tissue slides of bladder tumors from three pediatric patients were retrospectively identified from our institution's pathology archives (1990-present) and re-evaluated. Clinical data was reviewed. FGFR3, H-RAS, and PI3K mutational analysis of the most well-known mutated spots was conducted by PCR amplification and Sanger sequencing. IHC analysis was conducted using antibodies against p53, Pten, Rb, EGFR, Her2Neu and ki-67. Results: Two patients had low-grade Ta disease, whereas the other tumor was classified as a Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP). None of the lesions recurred. Two patients were female and one was male. The ages at diagnosis were 13, 11, and 17, with a mean follow-up of 5.2 years (Range: 1.5-8.0 years). All specimens showed H-RAS G12V mutation, whereas they were characterized by wild-type FGFR3 and PI3K. Nuclear p53 was not detected, whereas PTEN and Rb expression were maintained. EGFR was homogenously expressed in the three cases, and Her2Neu was negative. The proliferation rate analyzed by Ki-67 expression was very low in all cases (<5%). Conclusions: Pediatric tumors may arise from a pathway that is not initiated by FGFR3 or p53 mutations, but by H-RAS mutations. This distinction may explain the relatively few recurrences seen in the pediatric population. Molecular investigation of larger series of pediatric tumors is warranted, and will aid in determining the surveillance and the clinical follow up, if any, needed in this rare entity.

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Ki67 as a prognostic factor in low grade serous ovarian cancer (LGSOC): A retrospective analysis of the Tumor Bank Ovarian Cancer (TOC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5562 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5562-5562 ◽

Cited By ~ 1

Author(s):

Jalid Sehouli ◽

Helmut Plett ◽

Rolf Richter ◽

Carsten Denkert ◽

Silvia Darb-Esfahani ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Outcome ◽

Hot Spot ◽

Survival Rates ◽

Histological Evaluation ◽

Low Grade ◽

Ki 67 ◽

Platinum Based Chemotherapy ◽

Response To Chemotherapy ◽

The Impact

5562 Background: LGSOC is a rare and distinct entity characterized by younger age, lower response to chemotherapy and better clinical outcome. Aim of this study was to evaluate the impact of Ki67, estrogen and progesterone receptors (ER and PR) on platinum response and survival in primary LGSOC patients. Methods: 80 primary LGSOC patients with available FFPEs were identified within TOC. The histology was confirmed at a second histological evaluation. For Ki67 analysis conventional immunohistochemical staining was performed with the Mib-1 clone on Ventana. Slides were explored with a light microscope camera. A representative field for Ki-67 evaluation was selected, in case of heterogeneous staining a hot spot was chosen. The software classified detected cells into non-tumor, negative and positive cells. When necessary, a correction of tumor and non-tumor areas was performed by an experienced pathologist. The counted cells ranged between 175 and 2398. Overall the method allows a precise, continuous and standardized means to quantify Ki-67. ER and PR status was determined on scanned IHC TMA slides. ER and PR positive tumors were defined if the percentage of stained tumor cells was at least 10%. Statistical analysis was performed using IBM SPSS Statistics. Results: Median age at diagnosis was 56 years (range: 20-81), 81.3% of patients presented in advanced stage and 96.3% received platinum based chemotherapy. Ki67 median value was 5.09 (IQR: 1.56-10.5). 93.1% and 47.9% of the patients showed ER and PR positive tumors, respectively. Median overall survival (OS) was 45.5 months (range: 0.1-182.8). Our analysis showed that platinum free interval (PFI) was significant longer in patients with lower Ki67 (p = 0.006). Higher proliferation rates were significant associated with poorer progression free (p = 0.011, HR = 1.039, 95%CI: 1.009-1.070) and OS rates (p = 0.001, HR = 1.059, 95%CI: 1.025-1.095). No differences in clinical outcome were seen in patients with different ER and PR status. Conclusions: This is the first study showing that higher Ki67 values correlate with shorter PFI and poorer survival rates in LGSOC, underlying the heterogeneous character of this disease.

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Continued observation of the natural history of low-grade ductal carcinoma in situ reaffirms proclivity for local recurrence even after more than 30 years of follow-up

Modern Pathology ◽

10.1038/modpathol.2014.141 ◽

2014 ◽

Vol 28 (5) ◽

pp. 662-669 ◽

Cited By ~ 58

Author(s):

Melinda E Sanders ◽

Peggy A Schuyler ◽

Jean F Simpson ◽

David L Page ◽

William D Dupont

Keyword(s):

Local Recurrence ◽

Natural History ◽

Ductal Carcinoma In Situ ◽

Carcinoma In Situ ◽

Ductal Carcinoma ◽

Low Grade ◽

History Of

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Evaluation of the In Situ Hybridization Signal Patterns of Liquid-Based Cytological Human Papillomavirus Specimens for Diagnosing Squamous Intraepithelial Lesion

ISRN Pathology ◽

10.5402/2011/219790 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9

Author(s):

Katsunari Ishida ◽

Makoto Nagasaki ◽

Masayuki Kobayashi ◽

Tatsushi Nakagawa ◽

Toru Nabika ◽

...

Keyword(s):

Human Papillomavirus ◽

Low Grade ◽

Squamous Intraepithelial Lesion ◽

Routine Testing ◽

Squamous Cells ◽

Intraepithelial Lesion ◽

Liquid Based Cytology ◽

Undetermined Significance

To examine the diagnostic utility for squamous intraepithelial lesion (SIL) by cytological in situ hybridization (c-ISH) for the human papillomavirus using liquid-based cytology specimens, we investigated c-ISH signal patterns in the cases of low-grade SIL (LSIL), atypical squamous cells of undetermined significance (ASC-US), and high-grade SIL (HSIL). Episomal (E) and/or integrated (I) signals were observed. Two signal patterns (E≧I or I>E) were obtained by counting the number of E+ or I+ cells. E≧I was specific to LSIL and ASC-US (10/12); I>E, to HSIL (9/11) (P<0.01, χ2 test), suggesting significant utility of c-ISH in diagnosing SIL. In the cell fraction, E≧I in large cells was dominant in LSIL. Two cases of I>E in large cells of LSIL showed HPV persistence and/or progression during follow-up. Thus, c-ISH is useful in routine testing for diagnosing cervical dysplastic lesions, especially for detecting LSIL suspected for progression.

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Angiomatosis of the breast: a clinicopathological and immunophenotypical characterisation of seven cases

Journal of Clinical Pathology ◽

10.1136/jclinpath-2019-205821 ◽

2019 ◽

Vol 72 (9) ◽

pp. 597-602 ◽

Cited By ~ 1

Author(s):

Paula S Ginter ◽

Patrick J McIntire ◽

Lina Irshaid ◽

Yi-Fang Liu ◽

Sandra J Shin

Keyword(s):

Clinical Presentation ◽

Tumour Size ◽

Primary Tumour ◽

Vascular Lesion ◽

Low Grade ◽

Ki 67 ◽

Common Clinical Presentation ◽

Thin Walled ◽

Distinguishing Features

AimsMammary angiomatosis is a rare, benign vascular lesion that morphologically mimics low-grade angiosarcoma (LGAS). To date, only occasional reports of this entity have been published, none of which included analysis by immunohistochemistry. The purpose of this study was to further characterise mammary angiomatosis by clinical, histological, and immunohistochemical means while emphasising distinguishing features from LGAS.MethodsSeven cases of primary mammary angiomatosis were evaluated. For one patient, a subsequent recurrence was also evaluated.ResultsAll patients were female with a median age at presentation of 51 years (range: 19–58 years). The most common clinical presentation was that of a palpable abnormality or mass (5/8) and the median primary tumour size was 3.1 cm (range: 2–9 cm). Of the six patients with follow-up, one developed a recurrence 6 years after initial presentation. Histologically, all cases were composed of variably sized ectatic, thin-walled vessels lined by flat normochromic endothelium diffusely infiltrating mammary stroma. Where present, lesional vessels infiltrated between and around terminal duct lobular units but not into individual intralobular stroma. Most cases (6/8) showed a combination of lymphatic-appearing and haemangiomatous-appearing vessels. Lymphatic-appearing vessels were D2-40 positive in all but one case. D2-40 was negative or weak in haemangiomatous-appearing vessels. All lesional vessels were CD31 positive. Ki-67 indices were <1% in all but one case (5%).ConclusionsMammary angiomatosis is a rare vascular lesion that shares clinical, morphological and immunohistochemical features with LGAS; however, certain key traits make the distinction possible.

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Ability of urovysion FISH analysis to select patients with low- or intermediate-risk non-muscle-invasive bladder cancer (LI-NMIBC) for decreased surveillance.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.283 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 283-283

Author(s):

H. M. Rosevear ◽

A. J. Lightfoot ◽

M. A. O'Donnell

Keyword(s):

First Year ◽

Fish Analysis ◽

Low Grade ◽

High Grade ◽

Genetic Changes ◽

Screening Intervals ◽

Muscle Invasive ◽

Initial Resection

283 Background: Recurrent LI-NMIBC is difficult to detect cytologically, requiring frequent cystoscopies. Urovysion's (Abbot Laboratories, Downers Grove, IL) fluorescent in situ hybridization assay (FISH) detects genetic changes associated with LI-NMIBC and may be useful in identifying patients for extended screening intervals. Methods: Charts of 54 consecutive patients with LI-NMIBC who underwent cystoscopy, cytology, and FISH analysis every 3 months for the first year after resection since 2004 were retrospectively identified and reviewed. We analyzed the number of tumors or high-grade cytologies that would have been missed if surveillance cystoscopy, cytology, and FISH analysis had not been done between 3 and 12 months post-resection for patients with a normal cystoscopy, cytology, and FISH analysis at 3 months after initial resection and compared those results to patients with normal cystoscopy, cytology, and abnormal FISH analysis. Results: Mean age of the 54 patients was 67 (range 25–89) and 41 were males. Thirty-nine patients had normal cystoscopy, cytology, and FISH analysis at 3-months follow-up. If no further surveillance was done until 1 year post-resection, 2 low-grade tumors (3 and 7 mm at 7 months post-resection) and 2 incidents of high-grade cytology would have been missed (4 of 39, 10%). Fifteen patients had normal cystoscopy and cytology but abnormal FISH analysis results at 3 months. If no further surveillance had been done until 1 year after resection, 6 tumors (6 of 15, 40%) (5, 8, 3, 3, 9, 2 mm at 5, 6, 6, 7, 9, 10 months post-resection) and no high-grade cytology would have been missed. Overall, statistically fewer patients with normal compared to abnormal FISH analysis at first follow-up developed tumors before 1 year (4 of 39 vs. 6 of 15, p=0.033). Conclusions: FISH analysis can be used to significantly increase our ability to select patients suitable for extended screening intervals. It may be prudent to include FISH analysis at the first post-resection follow-up before selecting patients with LI-NMIBC for an extended screening interval. [Table: see text]

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