Tamar Giorgadze

Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin

Distinction of primary skin adnexal carcinomas from cutaneous metastasis of adenocarcinomas is challenging. In this study, we evaluated podoplanin immunoreactivity in a series of primary skin adnexal tumors and adenocarcinomas metastatic to skin using a D2-40 antibody. The initial test series were composed of a total of 93 cases including 32 primary skin adnexal carcinomas, 46 benign primary adnexal tumors, and 15 cutaneous metastatic adenocarcinomas. We found that variable D2-40 reactivity was seen in all of the primary cutaneous carcinomas including sebaceous carcinomas (10/10), squamous cell carcinomas (10/10), porocarcinomas (4/4), trichilemmal carcinomas (4/4), skin adnexal carcinomas not otherwise specified (4/4), and in the majority of benign skin adnexal tumors. In contrast, no podoplanin immunoreactivity was seen in any of the 15 (0/15) cutaneous metastases. To confirm the initial findings and to further explore the utility of podoplanin reactivity in the distinction of these tumors, we also examined a test set of 35 unknown cases, including 21 adenocarcinomas metastatic to skin and 14 primary adnexal tumors, in a blinded fashion. In this test set of cases, podoplanin was negative in 22 cases and positive in 13 cases. Of the 22 podoplanin negative cases, 20 were proven to be metastatic adenocarcinoma. Of the 13 D2-40 positive cases, 12 were proven to be primary adnexal tumors. Our results suggest that podoplanin can be a useful tool to distinguish primary skin adnexal carcinomas form adenocarcinomas metastatic to skin with high sensitivity (94.5%) and specificity (97.2%).

Lymphatic vessel density is significantly increased in melanoma

Background:  Melanoma is well known for its ability to involve regional lymph nodes in the early stage. However, the presence of lymphangiogenesis in melanoma is still controversial due to lack of lymphatic‐specific markers. The purpose of this study was to determine the intra‐ and peritumoral lymphatic vessel density (LVD) using a novel lymphatic vessel‐specific marker D2‐40 and compare it to general vessel density (GVD) as determined by CD31 immunostaining in a series of melanocytic lesions.

Diagnostic utility of mucin profile in fine-needle aspiration specimens of the pancreas: an immunohistochemical study with surgical pathology correlation.

The cytologic differentiation between neoplastic and reactive/reparative processes in the endoscopic ultrasound‐guided fine‐needle aspirations (EUS‐FNA) of the pancreas can be difficult. Malignant transformation of the pancreatic ductal epithelium changes the expression of apomucins. The goal of the current study was to determine an optimal immunohistochemical panel of mucin (MUC) antibodies that would allow the cytomorphologic distinction of pancreatic ductal adenocarcinoma and its differentiation from reactive/reparative processes and inadvertently sampled gastric and duodenal mucosa.

Lymphatic and blood vessel density in the follicular patterned lesions of thyroid

The histologic distinction of follicular patterned lesions of thyroid, that is follicular adenoma, follicular carcinoma, and the follicular variant of papillary thyroid carcinoma can be extremely difficult. The differential diagnostic criteria regarding nuclear features of papillary thyroid carcinoma are subjective, resulting in high interobserver variability. Although papillary thyroid carcinoma metastasizes mainly via lymphatic vessels, whereas follicular carcinoma spreads mostly hematogenously, there are no data regarding utility of objective quantitative criteria such as lymphatic and general blood vessel density for the differential diagnosis of these lesions. In this study, 35 follicular patterned lesions of thyroid (14 follicular adenomas, 10 follicular carcinomas, and 11 of the follicular variant of papillary thyroid carcinomas) were evaluated immunohistochemically. An assessment of intra- and peritumoral lymphatic vessel density was performed using novel lymphatic endothelium-specific marker D2-40, and the intra- and peritumoral general vessel density was determined by the panendothelial marker CD31. There were no significant differences in the intra- and/or peritumoral general vessel densities, and peritumoral lymphatic vessel densities among follicular adenoma, follicular carcinoma and the follicular variant of papillary thyroid carcinoma. In contrast, the intratumoral lymphatic vessel density was significantly higher in the follicular variant of papillary thyroid carcinoma than in either follicular adenoma or follicular carcinoma (34.63, 15.04, and 0.11 respectively; P<0.0001). The results of the study show that intratumoral lymphatic vessel density may serve as a useful tool in the differential diagnosis of follicular patterned lesions of thyroid.

Eosinophilic/T-cell Chorionic Vasculitis: A Clinicopathologic and Immunohistochemical Study of 51 Cases

We report 51 placentas diagnosed with eosinophilic/T-cell chorionic vasculitis (E/TCV), an unusual form of chorionic vasculitis characterized by an infiltrate composed predominantly of CD3+ T cells and eosinophils. The placentas were all 3rd trimester, with 48 (94.1%) being term. Forty-seven (92.2%) were singleton placentas, and the remaining 4 were twins. The E/TCV was limited to 1 chorionic surface vessel in 40 (78.4%) and involved 50% or less of the vessel circumference in 30 (58.8%) placentas. The inflammation faced the intervillous space in 12 (23.5%) and the amniotic cavity in 8 (15.7%) and had no distinct predominant direction in the remaining 31 (60.8%) placentas. Twelve (25.5%) placentas showed mural thrombi or intramural fibrin in association with the E/TCV. One hundred six term singleton placentas were selected as the control group, and the 47 singleton placentas with E/TCV made up the study group for comparison of demographic and histopathologic features. Villitis of unknown etiology was identified more frequently in study group placentas (20 [42.6%]) compared with control group placentas (14 [13.2%]) (P < 0.001). Vascular changes of fetal vascular thrombo-occlusive disease were identified away from the E/TCV more frequently in study group placentas (8 [17.0%]) compared with control group placentas (4 [3.8%]) (P = 0.008). There were no significant differences in the frequencies of other placental lesions studied, including acute inflammatory lesions and lesions related to maternal underperfusion. There were no significant differences in maternal age, race, parity, birth weight, allergy history, blood type, or medication use.

Phyllodes tumor metastatic to thyroid Hürthle cell adenoma.

We present a case of a malignant phyllodes tumor metastasizing to a Hürthle cell adenoma of the thyroid. A 55-year-old woman underwent mastectomy for a malignant phyllodes tumor. Two years later, she presented with a left thyroid mass, which was a single, circumscribed, soft, deep red-brown nodular lesion with an eccentric area of firmer consistency. Histologically, the thyroid tumor was composed of 2 distinct types of cellular proliferation. Atypical spindle cells were infiltrating between the Hürthle cell cords and follicles in a fibrosarcomatous pattern. A battery of immunohistochemical stains was applied to both the thyroid and breast tumors for comparison. Based on the histologic and immunophenotypic features of the fibrosarcomatous components of both the breast and thyroid tumors, we rendered a diagnosis of cystosarcoma phyllodes metastatic to Hürthle cell adenoma. To the best of our knowledge, this unusual case is a first report of tumor-to-tumor metastasis of a sarcoma to a primary thyroid neoplasm.

Dual color multiplex TTF-1 + Napsin A and p63 + CK5 immunostaining for subcategorizing of poorly differentiated pulmonary non-small carcinomas into adenocarcinoma and squamous cell carcinoma in fine needle aspiration specimens

Background: The distinction of lung adenocarcinoma (ADC) from squamous cell carcinoma (SCC) has important therapeutic implications. Napsin A is a recently developed marker, which has shown high specificity for lung tissue in the surgical pathology specimens. In this study, we have evaluated whether the use of a panel of novel multiplex cocktails of TTF-1 + Napsin A and p63 + CK5 for dual color immunostaining will improve the diagnostic accuracy of lung adenocarcinoma and squamous cell carcinoma in fine needle aspiration (FNA) specimens, usually with relatively scant microfragments of diagnostic material. Materials and Methods: Formalin-fixed, paraffin-embedded, adequately cellular FNA cell blocks with a confirmed diagnosis of either ADC (n = 22), SCC (n = 20) or poorly differentiated carcinoma (PDC; n = 7), from a total of 49 consecutive cases, were studied. All these cases had subsequently confirmed diagnosis in biopsies or resection specimens. The sections were immunostained with two color methods of TTF-1 + Napsin A and p63 + CK5 multiplex cocktails. The presence of one or more unequivocal individual tumor cells with convincing brown nuclear TTF-1 and red cytoplasmic Napsin A staining, and cells with brown nuclear p63 and membranous / cytoplasmic CK5 staining were interpreted as ‘positive’. Results: All 20 FNA cell blocks from SCC cases were positive for dual stain p63 + CK5 and negative for dual stain TTF-1 + Napsin A. The sensitivity and specificity of the dual immunoexpressions of p63 + CK5 for SCC of lung FNAs were both 100%. All 22 ADC cases were positive with dual stain of TTF-1 + Napsin A and negative for dual stain of p63 + CK5. On follow-up of the surgical pathology specimens, 22 cases were confirmed as ADC. The sensitivity of the dual immunoexpression of TTF-1 + Napsin A for ADC of lung FNAs was 100% and the specificity was also 100%. Of the seven PDC cases, five cases that were positive for dual stain p63 + CK5 and negative for dual stain TTF-1 + Napsin A could be categorized as SCC. Two of the seven (2 / 7) PDC cases were positive for dual stain TTF-1 + Napsin A and negative for dual stain p63 + CK5, consistent with ADC. Conclusions: Simultaneous coordinate or individual immunostaining for Napsin A / TTF-1 in ADC and p63 / CK5 in SCC demonstrated high sensitivity and specificity. The panel with multiplex Napsin A / TTF-1 and p63 / CK5 dual color immunostains could specifically subcategorize PDC into ADC and SCC in lung FNA specimens. Multiplex dual color Napsin A / TTF-1 and p63 / CK5 immunostaining is especially recommended for evaluation of FNA specimens with relatively scant cellularity.

Diagnostic utility of snail in metaplastic breast carcinoma

Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer characterized by coexistence of carcinomatous and sarcomatous components. Snail is a nuclear transcription factor incriminated in the transition of epithelial to mesenchymal differentiation of breast cancer. Aberrant Snail expression results in lost expression of the cell adhesion molecule E-cadherin, an event associated with changes in epithelial architecture and invasive growth. We aimed to identify the utility of Snail, and of traditional immunohistochemical markers, in accurate MBC classification and to evaluate clinicopathologic characteristics and outcome.We retrospectively reviewed 34 MBC cases from January 1997 to September 2007. The control group contained 26 spindle cell lesions. Immunohistochemistry used Snail, p63, epidermal growth factor receptor (EGFR), OSCAR, and wide spectrum cytokeratin (WS-KER). Negative was a score less than 1%. We found that Snail and EGFR are sensitive (100%) markers with low specificity (3.8% and 19.2%) for detecting MBC. p63 and WS-KER are specific (100%), with moderate sensitivity (67.6% and 76.5%); OSCAR is sensitive (85.3%) and specific (92.3%). A combination of any 2 of the p63, OSCAR, and WS-KER markers increased sensitivity and specificity. MBCs tended to be high-grade (77%), triple negative (negative for estrogen receptor, progesterone receptor, and HER2) [27/33; 81.8%], and carcinomas with low incidence of axillary lymph node involvement (15%), and decreased disease-free [71% (95%CI: 54%, 94%) at 3 yrs.) and overall survival. A combination of p63, OSCAR and WS-KER are useful in its work-up. On the other hand, Snail is neither a diagnostic nor a prognostic marker for MBC.

Fine-needle aspiration cytology of the solid variant of papillary thyroid carcinoma: A study of 13 cases with clinical, histologic, and ultrasound correlations

The solid variant of papillary thyroid carcinoma (SVPTC) comprises approximately 3% of thyroid cancers, and there are conflicting reports about its behavior in the literature. The cytology of SVPTC is limited to 3 single case reports, a review article, and a monograph. We present the first cytologic study of SVPTC.

Differential Expression of MicroRNAs in Papillary Thyroid Carcinoma and Their Role in Racial Disparity.

Objective MicroRNAs (miRNAs) are known to play important roles in the diagnosis and prognosis of papillary thyroid cancer (PTC), and they are useful in developing targeted therapies. However, there have been no studies on the existence of racial differences in miRNAs expression that could explain differential overall survival of PTC patients. Expression analysis of miRNAs in major racial groups would be important for optimizing personalized treatment strategies. In the current study, we assessed the differential expression of 8 miRNAs between normal and tumor tissues, and also assessed racial differences between African American (AA) and Caucasian American (CA). Methods First, the miRNA expression profiling was performed using formalin-fixed paraffin embedded (FFPE) tissue sections of tumor containing over 70% tumor cells. Normal and tumor sections of thyroid tissues were studied from AA and CA patients. The miRNA microarray profiling was done using miRBase version 18 (LC Sciences, Houston, TX, USA). Quantitative real-time PCR (qRT-PCR) was used to validate expression of 8 selected miRNAs. Results Ingenuity pathway analysis showed involvement of target genes, such as Ras and NF-κB. Deregulated miRNAs such as miR-221 and miR-31 were found to be statistically significant between the two races. Using qRT-PCR, we found that miR-21, miR-146b, miR-221, miR-222, miR-31, and miR-3613 were up-regulated while miR-138 and miR-98 were down-regulated in tumors compared to normal tissues. Conclusion Though sample size was small, we found several deregulated miRNAs having racial differences. The differential expression of miRNAs suggest that these miRNAs and their target genes could be useful to gain further mechanistic insight of PTC and their clinical implications, including miRNA replacement therapy or their knockdown strategies.