Applied immunohistochemistry & molecular morphology : AIMM最新文献

{"title":"Analysis of PIK3CA mutations in breast cancer subtypes.","authors":"Ruza Arsenic,&nbsp;Annika Lehmann,&nbsp;Jan Budczies,&nbsp;Ines Koch,&nbsp;Judith Prinzler,&nbsp;Anke Kleine-Tebbe,&nbsp;Christiane Schewe,&nbsp;Sibylle Loibl,&nbsp;Manfred Dietel,&nbsp;Carsten Denkert","doi":"10.1097/pdm.0b013e318297afea","DOIUrl":"https://doi.org/10.1097/pdm.0b013e318297afea","url":null,"abstract":"<p><p>Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) is a central element of a signaling pathway involved in cell proliferation, survival, and growth. Certain mutations in this pathway result in enhanced PI3K signaling, which is associated with oncogenic cellular transformation and cancer. The aims of this study were to characterize different types of PIK3CA mutations in exons 9 and 20 in a series of primary breast carcinomas and to correlate the results with clinicopathologic parameters and survival. We used frozen tissue samples and sequenced exons 9 and 20 for a series of 241 patients with a diagnosis of breast carcinoma. We found that 15.8% of the primary breast carcinomas possessed PIK3CA mutations in either exon 9 or exon 20. The rate of PIK3CA mutations was increased in HR(+)/HER2(-) tumors (18.6%), but this difference did not reach a statistical significance. The lowest rate of mutations was observed in HR(+)/HER2(+) tumors (5.3%). No statistically significant association was found between the presence of PIK3CA mutations and the prognostic/clinical features of breast cancer, including histologic subtype, Her2 status, axillary lymph node involvement, tumor grade, and tumor stage. However, the presence of the H1047R mutation in 10 samples was associated with a statistically significantly worse overall survival. PIK3CA mutation was found to be a frequent genetic change in all breast cancer subtypes but occurred with the highest rate in HR(+)/HER2(-) tumors. Further studies are needed to validate the prognostic impact of different PIK3CA mutations.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"50-6"},"PeriodicalIF":1.6,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/pdm.0b013e318297afea","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32067619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular analysis of the KIT gene in gastrointestinal stromal tumors with novel mutations.","authors":"Gizem Calibasi,&nbsp;Yasemin Baskin,&nbsp;Hakan Alyuruk,&nbsp;Levent Cavas,&nbsp;Ilhan Oztop,&nbsp;Ozgul Sagol,&nbsp;Koray Atila,&nbsp;Hulya Ellidokuz,&nbsp;Ugur Yilmaz","doi":"10.1097/PAI.0b013e318284a074","DOIUrl":"https://doi.org/10.1097/PAI.0b013e318284a074","url":null,"abstract":"<p><p>Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. KIT gene mutations have great importance for GISTs. This study evaluated the relationship between KIT mutations and GIST clinicopathologic features to define region-specific and population-specific differences. Genomic DNA was extracted from 60 GISTs, and polymerase chain reaction was performed for KIT gene exons 9, 11, 13, and 17. Polymerase chain reaction amplicons were sequenced in both directions. This study represents the first mutation data of the KIT gene in GISTs from a Turkish population and reports novel mutations. The mutation rate in exon 11 (46.7%) was remarkably higher than those of the other exons (8.3% for exon 9; 11.7% for exon 13; 1.7% for exon 17). There was an association between malignancy potential and the presence of KIT mutations (odds ratio=3.18). Cases with mutations in codons W557-K558 in exon 11 had 11-fold greater risk of malignancy when compared with those without a mutation in this exon (odds ratio=11). We report different mutations than those previously reported, which emphasizes the importance of personalized medicine that could be empowered by the use of bioinformatics tools in the diagnostic process and therapeutic approaches.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"37-45"},"PeriodicalIF":1.6,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/PAI.0b013e318284a074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31277144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ancillary diagnostic techniques in the evaluation of adult epithelial renal neoplasms: indications, caveats, and pitfalls.","authors":"Guillermo A Herrera,&nbsp;Elba A Turbat-Herrera","doi":"10.1097/PAI.0b013e318297d569","DOIUrl":"https://doi.org/10.1097/PAI.0b013e318297d569","url":null,"abstract":"<p><p>The role played currently by the different ancillary diagnostic techniques in the diagnosis of adult epithelial renal tumors continues to be debated. It has also become clear that in some instances light microscopic appearance alone cannot be used to classify these neoplasms into specific categories with the degree of precision required for therapeutic purposes. Renal cell carcinoma (RCC) subtypes may share common histologic characteristics but exhibit different biological behavior and response to therapy which clearly indicates the crucial role that advanced pathologic speciation plays in the current assessment of these neoplasms. Although immunohistochemistry is widely used for the purpose of categorizing renal tumors because of its widespread availability, the immunoprofiles of the various types of renal neoplasms overlap significantly, making definitive diagnostic determinations difficult and challenging at times. This manuscript will address how ancillary diagnostic techniques can be incorporated into the routine evaluation of neoplastic renal masses to improve classification. Both cytology and surgical specimens will be addressed, as fine needle aspiration (FNA) is being used with preference in many cases in the diagnosis of renal masses. Surgical and cytopathologists must intelligently select the ancillary diagnostic technique/s that will provide the information needed to solve the differential diagnosis under consideration in a given case. However, in some cases >1 of these techniques should be used to make an accurate diagnosis with the aim of arriving at an unequivocal diagnosis. The identification of specific signaling pathways that are defective in certain types of renal neoplasms has made possible the design of target-specific therapies that are directed towards the aberrant pathways associated with the defective proteins found in these tumors. This makes the exact classification of these neoplasms and the detection of these aberrant proteins targeted for treatment an absolute requirement for the application of these molecular-based therapeutic interventions. The role that the pathologic assessment plays in the classification of renal tumors becomes more important than ever to take advantage of this and similar new molecular-oriented therapies. </p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"77-98"},"PeriodicalIF":1.6,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/PAI.0b013e318297d569","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40267378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical pituitary adenoma with neurocytic transformation.","authors":"Fabio Rotondo,&nbsp;Marie Christine F Bernardo,&nbsp;Bernd W Scheithauer,&nbsp;Shahnila Latif,&nbsp;Christopher Bogaev,&nbsp;Aydin Sav,&nbsp;Kalman Kovacs","doi":"10.1097/PAI.0b013e3182634969","DOIUrl":"https://doi.org/10.1097/PAI.0b013e3182634969","url":null,"abstract":"<p><p>Here, we report an example of an atypical prolactin-producing pituitary adenoma showing clear morphologic and immunohistochemical evidence of neurocytic transformation. Its features support the concept that neoplastic neuroendocrine cells, in this case adenohypophyseal cells, are capable of neuronal differentiation and broaden the morphologic spectrum of such rare tumors. Our findings have implications with respect to the nosology of neuronal tumors of the adenohypophysis.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"72-6"},"PeriodicalIF":1.6,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/PAI.0b013e3182634969","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30850924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triple-negative, basal marker-expressing, and high-grade breast carcinomas are characterized by high lymphatic vessel density and the expression of podoplanin in stromal fibroblasts.","authors":"Joanna A Niemiec,&nbsp;Agnieszka Adamczyk,&nbsp;Aleksandra Ambicka,&nbsp;Anna Mucha-Małecka,&nbsp;Wojciech M Wysocki,&nbsp;Janusz Ryś","doi":"10.1097/PAI.0b013e318286030d","DOIUrl":"https://doi.org/10.1097/PAI.0b013e318286030d","url":null,"abstract":"<p><p>Podoplanin, expressed in the lymphatic but not in the blood vessel endothelium, is widely used as a specific marker for lymphatic endothelial cells and lymphangiogenesis. The relation between lymphatic vessel density and breast cancer subtype or the expression of basal markers has not yet been investigated. We assessed lymphatic vessel density (LVD), blood vessel density, and the expression of podoplanin in stromal cancer-associated fibroblasts, in 156 invasive ductal breast cancers (T≥1, N≥1, M0). Afterwards, we assessed the relationship between the above-mentioned parameters and (i) breast cancer subtype (luminal vs. HER2 vs. triple negative), (ii) tumor grade (G1 vs. G2 vs. G3), (iii) the expression of cytokeratin (CK) 5/6, (iv) P-cadherin, (v) smooth muscle actin (SMA), and (vi) the pattern/intensity of stromal lymphocytic infiltration. We found a significantly higher LVD and podoplanin expression in stromal fibroblasts in (i) G3 tumors, (ii) triple-negative carcinomas, (iii) tumors expressing CK5/6, SMA, or P-cadherin, and (iv) neoplasms with stroma intensively infiltrated by lymphocytes. Moreover, we observed a significant inverse relationship between the expression of podoplanin in luminal A subtype, P-cadherin, CK5/6, and SMA-negative tumors and tumors without strong lymphocytic infiltration. A significantly higher percentage of tumors with strong lymphocytic infiltration was noted among G3 carcinomas. Breast carcinomas of different grades, subtypes, and basal marker expression are characterized by different composition of the stroma, that is different LVD, podoplanin expression in stromal fibroblasts, and the pattern/intensity of lymphocytic infiltration.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"10-6"},"PeriodicalIF":1.6,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/PAI.0b013e318286030d","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31277145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Androgen receptor expression in vascular neoplasms of the breast.","authors":"Richa Jain,&nbsp;Pincas Bitterman,&nbsp;Ihab Lamzabi,&nbsp;Vijaya B Reddy,&nbsp;Paolo Gattuso","doi":"10.1097/PAI.0b013e31828b5116","DOIUrl":"https://doi.org/10.1097/PAI.0b013e31828b5116","url":null,"abstract":"<p><strong>Introduction: </strong>Androgen receptors (AR) have been reported to be present in normal breast tissue and breast carcinomas. The following study was undertaken to assess the expression of AR in vascular neoplasms of the breast.</p><p><strong>Materials and methods: </strong>All patients with histologically diagnosed hemangioma, angiolipoma, atypical vascular proliferation, and angiosarcoma of the breast were retrieved from the clinical and pathology database at Rush University Medical Center. The slides stained with hematoxylin and eosin were reviewed and immunohistochemical staining for AR (Dako; clone AR441) was performed on paraffin-embedded tissue. Any amount of nuclear staining was considered positive and the intensity of staining was graded as 1+ to 3+. An estimate of the percentage of tumor and stromal cells staining was made.</p><p><strong>Results: </strong>There were a total of 36 cases, 10 hemangiomas, 20 angiolipomas, 2 atypical vascular proliferation, and 4 angiosarcomas. The male to female ratio was 1:4.1. The average age at presentation for men was 45 years and for women was 56.9 years. Anti-AR expression was present in stromal and adipocyte nuclei of the angiolipomas and stromal cells of hemangiomas and angiosarcomas. Interestingly, normal duct epithelium of the breast was positive in 7 of the 29 women and none in men. Androgen expression was present in 62.5% of the hemangiomas, 55% of the angiolipomas, and 50% of the angiosarcomas. The majority of tumors showed a low-intensity nuclear expression of androgens, with 1+ intensity in 13 cases and 2+ intensity seen in 2 cases, and only 1 case of angiolipoma showed 3+ expression. All positive cases of angiolipoma (55%) showed AR in adipocytes and stromal cells.</p><p><strong>Conclusions: </strong>Vascular neoplasms are uncommon tumors in breast and majority of them are benign. Androgen expression is present in >50% of benign vascular neoplasms. Stromal cells and adipocytes typically express AR only in angiolipomas, suggesting a role of androgens in pathogenesis and growth of this neoplasm.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"132-5"},"PeriodicalIF":1.6,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/PAI.0b013e31828b5116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40228333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The significance of immunohistochemical expression of merlin, Ki-67, and p53 in meningiomas.","authors":"Sanda Pavelin,&nbsp;Kristijan Bečić,&nbsp;Gea Forempoher,&nbsp;Snježana Tomić,&nbsp;Vesna Capkun,&nbsp;Irena Drmić-Hofman,&nbsp;Ivana Mrklić,&nbsp;Ivo Lušić,&nbsp;Zenon Pogorelić","doi":"10.1097/PAI.0b013e318289f490","DOIUrl":"https://doi.org/10.1097/PAI.0b013e318289f490","url":null,"abstract":"<p><p>Meningiomas are one of the most common CNS tumors whose appearance is closely linked to NF2 gene product merlin. Tumor markers Ki-67 and p53 play established role in tumor progression which should be analyzed in close association with merlin expression. The aim of this study was to investigate the immunohistochemical expression of merlin in meningiomas, correlation with Ki-67 and p53, and to determine the association of these results with histologic grade and subtype. The histologic sections of 170 patients with totally resected meningiomas, between January 2000 and December 2010, were classified according to WHO, immunohistochemically stained for Ki-67, p53, and merlin, and analyzed using light microscope. Ki-67 median was 5.6 times higher in group of patients with negative merlin than in those with positive merlin (P=0.05). Statistically significant correlation of merlin with p53 was found (P<0.001). Merlin expression between 2 combined groups (meningothelial/secretory and fibroblastic/transitional) was statistically significant (P=0.002). By comparing merlin expression and p53 levels, statistically significant difference was found (P=0.017). In the group with positive merlin and negative p53 as well as positive merlin and low p53, meningothelial/secretory subtypes of meningiomas were more common. In combination of negative merlin and negative p53 as well as negative merlin and high p53, there were more meningiomas of fibroblastic/transitional subtype. There was no statistically significant correlation between merlin and tumor grade (P=0.420). There is undeniable influence of merlin on the development and the proliferative ability of meningioma subtypes. Significant role of p53 pathway was confirmed.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"46-9"},"PeriodicalIF":1.6,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/PAI.0b013e318289f490","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31277147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic findings and BRAF mutation in cutaneous melanoma in young adults.","authors":"Bruna Estrozi,&nbsp;Juliana Machado,&nbsp;Rubens Rodriguez,&nbsp;Carlos E Bacchi","doi":"10.1097/pdm.0b013e318298c1d9","DOIUrl":"https://doi.org/10.1097/pdm.0b013e318298c1d9","url":null,"abstract":"<p><p>Cutaneous melanoma in young patients is rare with increasing incidence. It is not clear whether the etiology and clinical outcome are similar to cutaneous melanoma in the elderly. Mutations in BRAF gene in patients with cutaneous melanoma, in general, range in frequency from 20% to 80%; however, the status and clinical significance of BRAF mutations in the young population have not been evaluated. We investigated 132 cases of primary cutaneous melanoma in patients aged between 18 and 30 years with emphasis on clinical characteristics, pathologic features, and molecular evaluation of mutation in the BRAF gene (BRAF(V600E)). It was predominantly seen in female individuals (61.4%), trunk was the most common site of involvement (40.4%), and superficially spreading melanoma was the predominant histologic type (79.5%). Mutation in BRAF(V600E) was analyzed successfully in 93 cases using an RT-PCR. The BRAF(V600E) mutation was identified in 38.7% (36/93) and was associated with vertical growth phase (P=0.01) and mild inflammatory infiltrate (P=0.02). No case of melanoma with regression phenomenon presented with BRAF(V600E) mutation (P<0.05). There was no significant association between BRAF(V600E) mutation and sex, histologic type, the Clark level, the Breslow index, solar elastosis, angiolymphatic and perineural invasion, satellitosis, and coexisting nevus. As in melanomas in older patients, these results probably indicate that BRAF mutation may not be the only key factor in melanoma tumorigenesis, and that there should be multiple alternative genetic pathways related to melanoma.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"57-64"},"PeriodicalIF":1.6,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/pdm.0b013e318298c1d9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32067620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping of succinate dehydrogenase losses in 2258 epithelial neoplasms.","authors":"Markku Miettinen, Maarit Sarlomo-Rikala, Peter McCue, Piotr Czapiewski, Renata Langfort, Piotr Waloszczyk, Krzysztof Wazny, Wojciech Biernat, Jerzy Lasota, Zengfeng Wang","doi":"10.1097/PAI.0b013e31828bfdd3","DOIUrl":"10.1097/PAI.0b013e31828bfdd3","url":null,"abstract":"<p><p>Losses in the succinate dehydrogenase (SDH) complex characterize 20% to 30% of extra-adrenal paragangliomas and 7% to 8% of gastric GISTs, and rare renal cell carcinomas. This loss is reflected as lack of the normally ubiquitous immunohistochemical expression of the SDH subunit B (SDHB). In paragangliomas, SDHB loss correlates with homozygous loss of any of the SDH subunits, typically by loss-of-function mutations. The occurrence of SDHB losses in other epithelial malignancies is unknown. In this study, we immunohistochemically examined 2258 epithelial, mostly malignant neoplasms including common carcinomas of all sites. Among renal cell carcinomas, SDHB loss was observed in 4 of 711 cases (0.6%), including a patient with an SDHB-deficient GIST. Histologically, the SDHB-negative renal carcinomas varied. There was 1 clear cell carcinoma with a high nuclear grade, 1 papillary carcinoma type 2, 1 unclassified carcinoma with a glandular pattern, and 1 oncocytoid low-grade carcinoma as previously described for SDHB-negative renal carcinoma. None of these patients was known to have paragangliomas or had loss of SDHA expression in the tumor. Three of these patients had metastases at presentation (2 in the adrenal, 1 in the retroperitoneal lymph nodes). There were no cases with SDHB loss among 64 renal oncocytomas. SDHB losses were not seen in other carcinomas, except in 1 prostatic adenocarcinoma (1/57), 1 lymphoepithelial carcinoma of the stomach, and 1 (1/40) seminoma. On the basis of this study, SDHB losses occur in 0.6% of renal cell carcinomas and extremely rarely in other carcinomas. Some of these renal carcinomas may be clinically aggressive. The clinical significance and molecular genetics of these SDHB-negative tumors requires further study.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"31-6"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714362/pdf/nihms454275.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40228335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spindle cell foci of the thyroid-mimicking malignancy: a diagnostic pitfall.","authors":"Andres Matoso,&nbsp;Salwa Khedr,&nbsp;Ronald A DeLellis,&nbsp;Shamlal Mangray","doi":"10.1097/PAI.0b013e31828b403d","DOIUrl":"https://doi.org/10.1097/PAI.0b013e31828b403d","url":null,"abstract":"To the Editor: We recently published a case series of spindle cell foci of the thyroid associated with multinodular goiter, follicular adenomas, and minimally invasive follicular carcinoma.1 Previously, Vergilio et al2 described spindle cell foci of the thyroid gland in association with papillary thyroid carcinoma and microcarcinoma. This uncommon entity is usually an incidental finding that consists of a spindle cell proliferation with nodular or diffuse distribution, bland cytologic features, low Ki-67 index, and an immunophenotype that supports a metaplastic follicular origin of the spindle cells. We previously emphasized the potential for confusion of spindle cell foci of the thyroid with medullary thyroid carcinoma, which is well demonstrated in this recent case that we reviewed on our consultation service. We report a 61-year-old woman who underwent a total thyroidectomy followed by cervical lymph node dissection after needle biopsy raised the concern for medullary thyroid carcinoma. Gross examination demonstrated the presence of two solid nodules measuring 1.6 and 0.7 cm in maximum diameter. Microscopic examination of sections of the nodule on the left lobe demonstrated an adenomatous nodule with macrofollicular architecture, extensive degenerative changes that included fibrosis and sclerosis along with florid spindle cell foci with infiltrative borders, and areas of eosinophilic interstitial deposits (Fig. 1). The spindle cells were arranged in sheets as well as in short fascicles, had elongated plump nuclei, fine chromatin, inconspicuous nucleoli, and variable eosinophilic cytoplasm (Figs. 1B, C). Intermixed cells with clear or foamy appearance were present. There was no evidence of mitotic activity or necrosis. Areas resembling desmoplastic stromal reaction associated with spindle cells were noted (Fig. 1E). The areas of sclerosis and fibrosis had an amorphous appearance simulating amyloid (Fig. 1F). A focus showing nuclear pleomorphism that merged with the spindle cell areas was noted in one section (Fig. 1F). Rare nuclear pseudoinclusions were also noted. Both the bland spindle cell component and the atypical cells had a low proliferation index on Ki-67 stain (<1%). All lymph nodes were negative for malignancy. Using immunohistochemistry, we found that the spindle cells were strongly positive for thyroid transcription factor-1 (TTF-1) and thyroglobulin but negative for cytokeratin AE1/3, synaptophysin, carcinoembryonic antigen (CEA), calcitonin, and CD56. Congo red stain was negative. Low Ki-67 along with the positive TTF-1 staining helps in excluding the possibility of anaplastic carcinoma. On the basis of these features, a diagnosis of adenomatous nodule with spindle cell foci consistent with spindle cell metaplasia of follicular cells was rendered. The atypical nuclei were interpreted as being consistent with “endocrine atypia”. As in the case presented here, all previous cases showed absence of necrosis, inflammation, or vascular ","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"577-8"},"PeriodicalIF":1.6,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/PAI.0b013e31828b403d","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40228332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}