Stromal Calcification Research Articles

Characterization of stromal calcifications in odontogenic keratocyst: a multicentric study.

Odontogenic keratocysts (OKCs) are locally aggressive cysts that exhibit typical histopathological features and have a propensity for recurrence. Though histological variations are observed in OKCs, hard tissue formation and metaplastic changes are rare, and the underlying pathogenesis is not well understood. This study aimed to characterize stromal calcifications andanalyze their association with odontogenic components in non-syndromic and syndrome-associated cases of OKCs. We analyzed 153 cases of OKCs from healthcare institutes in India and Japan. The epithelial and stromal features were evaluated, and the relationship of calcifications with odontogenic rests was determined. Immunohistochemistry for cytokeratin-19 and special stains including Masson Trichrome and Van Gieson, were used for identification of odontogenic rests and calcifications respectively. Stromal calcifications were observed in 29.41% OKCs. The calcification patterns included irregular dystrophic, dentinoid with linear or calcospherite-type mineralization, and psammoma calcifications. Psammoma and dentinoid calcifications were found in the proximity of cytokeratin-19-positive odontogenic rests or satellite cysts, whereas majority cases with dystrophic calcifications did not exhibit co-localization with stromal odontogenic components. Distinct patterns of calcifications were observed in OKCs. Calcifications found in proximity of the odontogenic rests were possibly indicative of an inductive or host-mediated response.

Correlations between the average Young's modulus and histopathological characteristics of papillary thyroid carcinoma

Objective: To explore the histopathological factors affecting the stiffness of papillary thyroid carcinoma (PTC). Methods: Ninety-six patients with PTC confirmed by surgery and pathology in Shanxi Bethune Hospital from January 2019 to December 2020 were selected, including 101 nodules. Two-dimensional ultrasound and shear-wave elastography (SWE) were performed before surgery and the average Young's modulus (Emean) of PTC nodules were measured. Histopathological examinations on the nodules were conducted after surgery to decide the lesion size, number of lesions, calcification type, presence or absence of capsular and extracapsular invasion, degree of fibrosis, microvessel density, and number of tumor cells. The correlations between the lesion size, degree of fibrosis, microvessel density, and number of tumor cells and the Emean were analyzed. The Emeans of nodules with different numbers of lesions, presence or absence of capsular and extracapsular invasion, and different pathological calcification types were compared. The multiple linear regression analysis was used to evaluate the histopathological factors influencing the Emean. Results: The ranges of the lesion sizes, degrees of fibrosis, microvascular density, numbers of tumor cells, and the Emeans of the 101 investigated PTC nodules were (1.29±0.95) cm, (30.64±18.37)%, (101.64±30.7) vessels per high power field, (373.52±149.87) cells per high power field, and (36.47±19.62) kPa, respectively. Correlation analysis showed that the lesion size of PTC and the degree of fibrosis were positively correlated with the Emean (r=0.660, P＜0.001; r=0.789, P＜0.001), while the microvessel density was negatively correlated with the Emean (r=-0.198, P=0.047). The Emean of the group with capsular and extracapsular invasion was higher than that of the group without (P=0.014). There were statistical differences in the Emeans among different types of pathological calcification (P＜0.001). The multiple linear regression analysis showed that the lesion size (β=0.325, P＜0.001), degree of fibrosis (β=0.563, P＜0.001), psammoma bodies (β=0.177, P=0.001), stromal calcification (β=0.164, P=0.003), and mixed calcification of both psammoma bodies and stroma (β=0.163, P=0.003) were independent influencing factors for the Emean. The degree of fibrosis had the greatest impact on the Emean. Conclusions: The Emean of PTC lesions was correlated with the histopathological characteristics of PTC. The lesion size, degree of fibrosis, and calcification had significant impact on the Emean, among which the degree of fibrosis had the greatest impact.

Correlation of pericoronal radiographic width with histopathology of dental follicle of impacted teeth using modified gallego's and H and E stain

Background: Dental follicles are involved the development of tooth and periodontal structures. Dental follicles are known for pleuripotency and inductive changes but are also known for origin for various pathologies. Materials and Methods: Fifty eight asymptomatic dental follicle tissues were examined histologically and radiographically wherein orthopantomogram radiographic width was correlated with various histological parameters of dental follicle and evaluated for the presence of various pathologies using modified Gallego's stain. Observation and Results: There was evidence of pathological changes associated with asymptomatic dental follicle. We also found variations in epithelial lining, stromal calcifications, and variable compositions. Conclusion: We encourage researchers to examine this peculiar tissue as a unique model and explore its potential to avoid future complications.

971 A Rare Case of a Reno-colic Fistula Presenting as a Retroperitoneal and Psoas Abscess

Abstract Background Fistulous connections arising between the kidney and colon are rare and develop due to multiple aetiologies. We present a rare case of a reno-colic fistula presenting unusually as a retroperitoneal and psoas abscess managed surgically with a good outcome. Case Report A 49-year-old lady presented with 5-day history of left flank pain and swelling with no significant surgical or medical history. Physical examination revealed a tender left renal angle with raised inflammatory markers (CRP and WCC). Computed tomography (CT) revealed an extensive collection extending from an atrophic left kidney through the retroperitoneum and psoas into the subcutaneous tissues with possible fistulation into the descending colon. This was initially treated with antibiotics and percutaneous drainage of the collection. A reno-colic fistula was confirmed via left retrograde pyelogram. Under the multidisciplinary care of the urology and colorectal general surgical teams she underwent a left nephrectomy, large bowel resection and defunctioning colostomy successfully and was discharged eight days later. Histology later confirmed an extensively scarred atrophic left kidney with multiple renal stones with no preserved glomeruli, focal inflammatory infiltrate and stromal calcification consistent with end stage nephropathy. With the resected 5 cm descending colon showing mucosal and serosal inflammation consistent with site of fistula. Conclusions Reno-colic fistula is rare and presentation with a retroperitoneal and psoas abscess uncommon. We report a rare case of a reno-colic fistula secondary to a chronically infected and obstructed left kidney managed surgically with a good outcome.

High-risk morphological features are less prevalent among small (<5mm) papillary thyroid microcarcinomas compared to larger (≥5mm) tumors: a study of 206 cases

AbstractIntroduction: Papillary thyroid microcarcinoma (PTMC) is defined as a PTC measuring 1 cm or less, incidentally discovered. The aim of this study was to determine whether small (<5mm) tumors by contrast with large (≥5mm) ones are less frequently associated with high-risk morphological features, predictive of tumor aggressiveness.Materials and methods: All consecutive PTMC cases registered at the Department of Pathology, Târgu-Mureş Emergency County Hospital between 2003-2014 were reviewed. The following have been assessed: tumor size, subcapsular versus nonsubcapsular location, extrathyroidal extension/invasion into the perithyroidal adipose tissue, multifocality, resection margins, lymph node involvement, histological variant, tumor border, stromal reaction (fibrosis/desmoplasia/sclerosis), presence of plump pink cells, nuclear features of the tumor cells, intratumoral lymphocytic infiltrate, multinucleated giant cells, psammoma bodies and stromal calcification. The cases were split in two categories: small (< 5mm) and large (≥ 5mm) PTMCs and the pathological features were evaluated in comparison.Results: Our study included 206 cases, 91 large and 115 small PTMCs, respectively. Large PTMCs were significantly associated with the presence of plump pink cells (p=0.002), well developed PTC nuclear features (p=0.003), stromal reaction (fibrosis/desmoplasia/sclerosis) (p<0.001), infiltrative tumor border (p=0.011), subcapsular location (p<0.001), positive resection margins (p=0.022), stromal calcifications (p<0.001) and intratumoral multinucleated giant cells (p<0.001). Small PTMCs were generally well circumscribed and nonsubcapsular.Conclusions: Our results have shown that small (<5mm) PTMCs are less frequently associated with high-risk morphological features, predictive of tumor aggressiveness compared with large (≥5mm) tumors and could thus be considered as low-risk cancers.

Postchemotherapy Associated Histopathological Findings in Invasive Breast Carcinoma: A Camouflaged Signature

Introduction: Breast cancer is the most common cancer diagnosed in women world-wide. Application of preoperative Neoadjuvant Chemotherapy (NACT) has become a frequently employed therapeutic approach to treat breast cancer patients. Such chemotherapy alters the morphology of both malignant tumour tissue and adjacent benign breast tissue. Aim: To compare the histopathological features in mastectomies done for invasive breast carcinoma among those who received NACT with those who had not received NACT. Materials and Methods: It was a retrospective observational study of invasive breast carcinoma cases conducted at a rural tertiary care referral institute, PES Institute of Medical Sciences and Research (PESIMSR), Kuppam, Andhra Pradesh, India, from January 2013 to April 2015. The histopathological features in mastectomies were evaluated using a modified scoring system and compared between those who received NACT (study group) and those who had not received NACT (control group). Postchemotherapy associated histopathological features were analysed for statistical significance. Frequencies, Chi-square test and crosstabs were the statistical tools used to analyse the data. All statistical calculations were done through Statistical Software Data (STATA) version 14.1. Results: Out of 24 cases analysed, the study group (mean age=53.67 years) and control group (mean age=45.92 years) constituted 12 cases each. In postchemotherapy cases, fibroelastosis (p-value= 0.027) was a significant feature in the malignant tumour tissue. Stromal fibrosis (p-value=0.036), epithelial atypia (p-value <0.0001) and calcification (p-value=0.002) were significant features in the benign breast tissue. Conclusion: In postchemotherapy cases, fibroelastosis was significant histopathological feature in malignant tumour tissue. Stromal fibrosis, epithelial atypia and calcification were significant histopathological features in the benign breast tissue. Such findings may be considered as camouflaged signature of chemotherapy. It may be hypothesised that calcification in the benign breast tissue may indicate a tell-tale sign of cell injury secondary to systemic chemotherapeutic agents.

Molecular Aspects of Thyroid Calcification.

In thyroid cancer, calcification is mainly present in classical papillary thyroid carcinoma (PTC) and in medullary thyroid carcinoma (MTC), despite being described in benign lesions and in other subtypes of thyroid carcinomas. Thyroid calcifications are classified according to their diameter and location. At ultrasonography, microcalcifications appear as hyperechoic spots ≤ 1 mm in diameter and can be named as stromal calcification, bone formation, or psammoma bodies (PBs), whereas calcifications > 1 mm are macrocalcifications. The mechanism of their formation is still poorly understood. Microcalcifications are generally accepted as a reliable indicator of malignancy as they mostly represent PBs. In order to progress in terms of the understanding of the mechanisms behind calcification occurring in thyroid tumors in general, and in PTC in particular, we decided to use histopathology as the basis of the possible cellular and molecular mechanisms of calcification formation in thyroid cancer. We explored the involvement of molecules such as runt-related transcription factor-2 (Runx-2), osteonectin/secreted protein acidic and rich in cysteine (SPARC), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteopontin (OPN) in the formation of calcification. The present review offers a novel insight into the mechanisms underlying the development of calcification in thyroid cancer.

Staining efficacy assessment of a differential routine and special stains for pathological stromal calcifications in maxillofacial lesions

ABSTRACT Head and neck connective tissue lesions may have diverse calcifications within the fibrous connective tissue stroma. The perplexity involved in the identification and determination of the nature or degree of calcification through routine hematoxylin and eosin (H&E) stains necessitates the usage of a specific, simple, and cost- and time-effective differential staining techniques. The aim of the present study was to develop criteria to distinguish bone formation from bone resorption using methylene blue-acid fuchsin (MB/AF) stain and the role of collagen fibers in the identification of stromal calcifications using polarizing microscopy with picrosirius red stain. Twenty cases with pathological diagnoses for various stromal calcifications in maxillofacial lesions were retrieved from the departmental archives. Decalcified formalin fixed paraffin embedded tissue sections were stained with hematoxylin and eosin, Masson’s trichrome (MT), methylene blue-acid fuchsin (MB/AF), and picrosirius red. The stained sections were assessed to identify the calcifications found in the surrounding connective tissue stroma. It was observed that most cases showed maximum staining intensity with MB/AF stain as compared to the other staining methods. Moreover, the results suggested that contrast between calcification and stromal soft tissue was best distinguished with the MB/AF stain except in the case of dystrophic calcifications. Along with this, polarizing microscopy with picrosirius red enables better characterization of stromal components. Although the H&E stain and a connective tissue stain i.e. Masson’s trichrome, are employed routinely in histopathology; the use of special stains such as MB-AF and picrosirius red facilitates the identification of calcifications from the stromal tissues.

Rapid, label-free detection of intracranial germinoma using multiphoton microscopy.

.Accurate histopathological diagnosis is essential for facilitating the optimal surgical management of intracranial germinoma. Current intraoperative histological methods are time- and labor-intensive and often produce artifacts. Multiphoton microscopy (MPM) is a label-free imaging technique that can produce intraoperative histological images of fresh, unprocessed surgical specimens. We employ an MPM based on second-harmonic generation and two-photon excited fluorescence microscopy to image fresh, unfixed, and unstained human germinoma specimens. We show that label-free MPM is not only capable of identifying various cells in human germinoma tissue but also capable of revealing the characteristics of germinoma such as granuloma, stromal fibrosis, calcification, as well as the abnormal and uneven structures of blood vessels. In conjunction with custom-developed image-processing algorithms, MPM can further quantify and characterize the extent of stromal fibrosis and calcification. Our results provide insight into how MPM can deliver rapid diagnostic histological data that could inform the surgical management of intracranial germinoma.

Relationship between ultrasonographic and pathologic calcification patterns in papillary thyroid cancer.

Ultrasonographic microcalcification is highly related to papillary thyroid cancer (PTC) and pathologic psammoma body is a poor prognostic factor. However, it is little known about whether the microcalcifications seen on ultrasonography are consistent with the pathologic psammoma bodies. We evaluated the relationship between ultrasonographic (US) calcification types and pathologic calcification features, and the consistency between observed pathologic and US calcifications.US calcifications were classified into microcalcification (MC) and nonmicrocalcification (non-MC) types, and pathologic calcifications were classified into 3 types: psammoma bodies, stromal calcifications, and ossifications.Among the 411 nodules that were reviewed by a pathologist, 38.9% (n = 160) had any type of US calcification. The larger the size of pathologic calcification, the more calcification was present in US (psammoma 46.1% < stromal 53.7% < ossification 73.3%). Psammoma bodies occurred in all US MC type. Ossification nodules occurred in nearly all (92.3%) non-MC type. The stromal-only nodules were 36.8% MC-type and 63.2% non-MC type. MC-type had a significantly higher odds ratio than non-MC type for predicting psammoma bodies according to the logistic regression.The presence of MC in ultrasonography was consistent with the presence of psammoma bodies. This study suggests that US identification of MC may be a useful prognostic indicator of PTC aggressiveness.

Stromal tiny black dots, like "sugar-coated", of von Kossa stain is a diagnostic clue to hyalinizing trabecular tumor of the thyroid gland.

Hyalinizing trabecular tumor (HTT) is a rare low-grade tumor, and a prominent feature is the basement membranous stroma. We assume that such characteristic stromal findings of HTT are related to calcium deposition, and examined HTT samples by von Kossa special staining. There has been no report describing von Kossa special staining for such stroma. We collected 12 cases of HTT and 30 cases of papillary thyroid carcinoma (PTC) that had matched age, gender, tumor size, and surgical procedure characteristics as a control group. We compared the staining pattern and degree of von Kossa positivity between HTT and PTC, and a grading system of von Kossa stain was adopted to highlight differences between them. On von Kossa staining, all HTT revealed many tiny black dots around vessels in the hyalinized stroma, like "sugar-coated", and a high degree of calcium deposition in most cases, whereas PTC showed sparse stromal calcification in some cases. The degree of von Kossa staining was significantly different between the two groups. This is the first report describing abundant tiny black dots, like a "sugar-coated" appearance, of von Kossa stain in HTT. Here, we propose this finding can be a useful diagnostic clue to HTT.

Patterns of Sonographically Detectable Echogenic Foci in Pediatric Thyroid Carcinoma with Corresponding Histopathology: An Observational Study.

Small echogenic foci within pediatric thyroid nodules are commonly seen by ultrasound and are one of the features used to determine the level of suspicion for malignancy. These are sometimes termed "microcalcifications," but their relation with malignancy is controversial due to the lack of standard terminology. Our aim was to evaluate sonographic patterns of echogenic foci in malignant pediatric thyroid nodules and describe the distribution of corresponding psammoma bodies and other histopathologic findings in thyroidectomy specimens. Ultrasounds of 15 pathologically proved malignant thyroid nodules in children were retrospectively reviewed by 2 radiologists who separately classified echogenic foci into the 4 morphologic patterns described in the American College of Radiology Thyroid Imaging, Reporting and Data System and noted their presence and distribution. Interobserver agreement was assessed, and consensus was reached for nodules for which there was disagreement. Surgical pathology findings from thyroidectomy specimens were retrospectively reviewed for the presence and distribution of psammomatous and dystrophic/stromal calcifications and eosinophilic/sticky colloid. Ultrasound and histopathologic ratings were compared, and frequencies and percentages corresponding to observed agreement levels were calculated. Interobserver agreement between radiologists' sonographic assessments for the presence and distribution of echogenic foci ranged from 53% to 100% for all categories. Punctate echogenic foci were present in all nodules, and macrocalcifications, in 27%. Histopathology of the 15 nodules revealed that only 4 (27%) had psammomatous calcifications, while 9 (60%) had stromal calcifications and 8 (53%) had sticky colloid. Sonographically detectable echogenic foci in malignant pediatric thyroid nodules can be reliably classified on the basis of American College of Radiology Thyroid Imaging, Reporting and Data System, with punctate echogenic foci composing the most common subtype. These echogenic foci do not represent psammomatous calcifications most of the time; instead, more than half of the malignant thyroid nodules with echogenic foci contained stromal calcifications or sticky colloid.

PD-L1 and PD-1 expression are correlated with distinctive clinicopathological features in papillary thyroid carcinoma

BackgroundImmune checkpoint blockade targeting PD-1/PD-L1 has shown efficacy in several types of cancers. However, the correlation between PD-L1/PD-1 expression and the specific clinicopathological features in papillary thyroid carcinoma (PTC) has not been investigated.MethodsWe examined the immunohistochemical expression of PD-L1, PD-1, and BRAF V600E on whole-tissue sections from 126 cases of primary PTC more than 1 cm in size. The correlation between the PD-L1/PD-1 expression and the clinicopathological features was evaluated.ResultsPD-L1 was positively expressed in 53.2% PTCs, and its expression was positively correlated with rich tumor-infiltrating lymphocytes (TILs), background chronic lymphocytic thyroiditis (CLT), female gender, absence of psammoma bodies, and PD-1 expression. Among these parameters, rich TILs, female gender, and absence of psammoma bodies were independent factors affecting PD-L1 expression on the multivariate logistic regression analysis. PD-1 expression was detected in the TILs and was positively correlated with rich TILs, background CLT, and absence of stromal calcification. Lack of stromal calcification was an independent factor affecting PD-1 expression. Neither PD-L1 nor PD-1 expression showed significant correlation with BRAF V600E expression.ConclusionsOur results show that the distinctive pathological features of PTCs, including TILs, background CLT, female gender, psammoma bodies, and stromal calcification, are useful parameters for predicting PD-L1 or PD-1 expression.

Abstract MIP-074: CLUES FOR THE ORIGIN OF MUCINOUS OVARIAN TUMORS IN BRENNER TUMORS AND TERATOMAS?

Abstract PURPOSE The origin of primary mucinous ovarian carcinomas is unknown. We investigated the possible relation between mucinous ovarian tumors and Brenner tumors and teratomas to identify the cell of origin, which might provide clues for future therapies. EXPERIMENTAL PROCEDURES In total, 104 Brenner tumor-associated mucinous tumors (BAMT) and 58 teratoma-associated mucinous tumors (TAMT) were collected. All cases were revised and diagnosis, age, laterality, size, distributional pattern of Brenner nests and mucinous cysts, presence of mucinous metaplasia of Brenner nests, presence of mucinous stromal dissection and calcifications were scored. If the Fallopian tube was resected, presence of Walthard nests and transitional cell metaplasia was scored. On 37 BAMT and 24 TAMT, immunohistochem-istry for CK7, CK20, CDx2, HNF4α, SATB2, OC125, PAX-8, WT-1, p53, MUC4, CEA, ER, PR, Ki-67, PMS2, MSH2, MSH6, MLH1 and HER2 and Fluorescence In Situ Hybridization (FISH) for Her2/neu and c-Myc was performed. Also, Comparative Genomic Hybridization (CGH) for copy number analysis was carried out. RESULTS Patients with TAMT were significantly younger than patients with BAMT (44.0 vs. 61.3 years respectively, p&amp;lt;0.01). Mucinous stromal dissection occurred more often in TAMT (43% vs. 13%, p&amp;lt;0.01), whereas in BAMT calcifications (56% vs. 22%, p&amp;lt; 0.01) and Wal-thard cell nests (42% vs. 15%, p&amp;lt;0.01) occurred more often. BAMT rarely expressed SATB2 (3% vs. 42%, p&amp;lt;0.01). During progression from cystadenoma to atypical proliferative mucin-ous (borderline) tumor (APMT) to carcinoma in BAMT, there was a significant increase in expression of typical gastrointestinal markers CK20 (18%, 81%, 100%, p&amp;lt;0.01), CDx2 (13%, 75%, 100%, p&amp;lt;0.01), CEA (29%, 81%, 75%, p&amp;lt;0.01) and HNF4 (71%, 100%, 100%, p=0.03). In TAMT, similar trends where observed without reaching statistical significance. For CK20, CDx2, HNF4α and MUC4 Brenner components showed no staining. WT-1 was positive in 47% of Brenner tumors, but only in 3% of associated mucinous tumors. All 3 tera-toma associated carcinomas showed wild type p53, in contrast to 3 out of 4 Brenner associat-ed carcinomas showing expression patterns matching mutated p53. Mismatch repair protein expression was normal in all carcinomas. One Brenner tumor associated carcinoma and one teratoma associated APMT showed positive Her2/neu status. No Brenner tumors were posi-tive for Her2/neu. No c-Myc amplification was noted. Results of CGH are pending. CONCLUSION Teratomas and Brenner tumors give rise to different subtypes of mucinous ovarian tumors, with different demographic and histological presentation. Remarkably, both TAMT and BAMT progress to a gastrointestinal phenotype, suggesting the commonly applied routine immunohistochemistry a poor tool for detection of origin. Citation Format: Michiel Simons, Johan Bulten, PALGA Group, Leon F Massuger, Iris D Nagtegaal, Robert J Kurman. CLUES FOR THE ORIGIN OF MUCINOUS OVARIAN TUMORS IN BRENNER TUMORS AND TERATOMAS? [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-074.

Correlation between Ultrasound Elastography and Histologic Characteristics of Papillary Thyroid Carcinoma

The aim of this study was to investigate the correlation between elastography and histologic characteristics including fibrosis and calcification. We also wanted to investigate whether other clinicopathologic indexes influence the strain ratio (SR) of papillary thyroid carcinomas (PTCs). We retrospectively reviewed 126 papillary thyroid carcinomas (PTCs) from 103 patients who underwent ultrasonography and elastography before surgery. The histologic characteristics and clinicopathologic indexes were compared with the SR of ultrasound elastography (UE). The results showed that there was a significantly positive correlation between fibrosis degree and SR measurements (r = 0.754, p = 0.000); the SR was significantly different between the groups with and without calcification (11.34 ± 10.08 vs. 6.81 ± 7.33, p = 0.000). The standard coefficients of collagen and stromal calcification were 0.684 and 0.194, respectively. There was no significant correlation between SR and indices such as size, position, co-existence with Hashimoto’s thyroiditis (HT), multifocality or cervical lymph node (CLN) metastasis. In conclusion, we found that the SR of UE is positively correlated with the fibrosis of PTC. Stromal calcification will elevate the SR dramatically, but psammoma bodies will not when they exist in the absence of stromal calcification.

Correlation between the histological features of corneal surface pannus following ocular surface burns and the final outcome of cultivated limbal epithelial transplantation

Background/aimsTo report the influence of histological features of corneal surface pannus following ocular surface burn on the outcome of cultivated limbal epithelial transplantation (CLET).MethodsOn retrospectively reviewing the medical records of...

Mammographic Signs of Systemic Disease

: Although mammography is primarily used for the detection of breast cancer, it can occasionally reveal breast abnormalities related to extra-mammary disease. Cardiovascular diseases such as congestive heart failure and central venous obstruction may manifest as venous engorgement and breast edema at mammography. Pathologic arterial calcifications seen at mammography can indicate an underlying risk factor for accelerated atherosclerosis such as chronic renal failure. Connective tissue diseases including rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis-polymyositis, and systemic scleroderma typically manifest with bilateral axillary lymphadenopathy, and stromal calcifications are also seen in the latter three disease processes. Some diseases such as neurofibromatosis type 1 and filariasis may manifest with pathognomonic findings at mammography, whereas other systemic diseases such as Wegener granulomatosis, sarcoidosis, and amyloidosis can manifest as nonspecific breast masses that are indistinguishable from breast cancer and usually require tissue biopsy for confirmation. Knowledge of the imaging characteristics of various systemic diseases affecting the breast will aid the radiologist in differentiating systemic disease from suspect breast lesions, thereby, helping ensure appropriate follow-up. Furthermore, recognition of systemic diseases such as Cowden syndrome that are associated with an increased risk of breast cancer will allow the radiologist to recommend appropriate surveillance.

Expression profile of endothelin 1 and its receptor endothelin receptor A in papillary thyroid carcinoma and their correlations with clinicopathologic characteristics

The endothelin axis is a group of signaling molecules and their receptors that have been implicated in vascularization of cancers, with their expression being observed to change in different cancer types. In this research, we examined the expression of endothelin 1 and endothelin receptor A at the protein and messenger RNA (mRNA) levels in 123 papillary thyroid carcinomas and 40 matched lymph nodes with metastatic papillary thyroid carcinomas. We found altered endothelin axis mRNA expression in several clinicopathologic parameters with increased endothelin 1 expression in thyroid papillary carcinoma showing stromal calcification, cancers in men, and primary cancers with lymph node metastases. Increased endothelin receptor A mRNA expression was noted in the larger cancers. There is a significant correlation between expression of endothelin receptor A and endothelin 1 in papillary thyroid carcinoma. Both endothelin receptor A and endothelin 1 mRNA expressions were significantly higher in metastatic carcinoma in the lymph node than in primary thyroid cancer. The metastatic carcinoma in the lymph node had increased expression compared with matched primary thyroid carcinoma. Expressions of endothelin 1 and endothelin receptor A were also documented as being high at the protein level. Our results indicate that in thyroid cancer, endothelin 1 and endothelin receptor A are associated with growth in advanced stages and lymph node metastases, likely through known angiogenic linkages. Targeting the endothelin axis may be useful in planning angiogenesis therapy for thyroid cancer.

Visual Diagnosis: A 31/2-year-old Boy With Sickle -Thalassemia and a Groin Mass

1. Aditi Bagchi, MD* 2. Ashraf Elnawawi, MD† 3. Swayam Sadanandan, MD‡ 1. *Resident (PGY-3), Pediatrics, The Brooklyn Hospital Center, Brooklyn, NY. 2. †Attending Physician, Department of Pathology, The Brooklyn Hospital Center, Brooklyn, NY. 3. ‡Associate Chairperson, Department of Pediatrics, Chief, Division of Pediatric Hematology and Oncology, The Brooklyn Hospital Center, Brooklyn, NY. * Abbreviations: CFP: : calcifying fibrous pseudotumor IMT: : inflammatory myofibroblastic tumor A 3½-year-old boy with a history of sickle β-thalassemia presents to the hematology/oncology clinic for evaluation of a mass in his left groin. The child’s mother had noted a small lump in his left inguinal region 2 years ago. At that time, the pediatrician recommended observing the lump and monitoring any progression. Subsequently, the family moved out of town and did not seek further medical attention until now. Two weeks ago, his mother thought the mass had grown in size and brought him to a nearby hospital for evaluation. He was prescribed a 5-day course of oral antibiotics for a presumed local infection. However, there was no significant change in the size of the mass; so his mother brought him to the hematology/oncology clinic. There is no history of groin pain or erythema, abdominal pain, fever, weight loss, or change in bowel or bladder habits. There is no history of trauma. The child was born at term after an uncomplicated pregnancy and delivery, but newborn screening indicated sickle cell disease. On further evaluation, his mother was found to have β-thalassemia trait and his father had sickle cell trait. The patient was diagnosed as having sickle β-thalassemia and placed on penicillin prophylaxis and folic acid supplementation. Since then, he has had four hospitalizations for febrile illnesses but no history of documented bacteremia. He has not had any vaso-occlusive crises. His motor milestones are appropriate for age, with the exception of speech delay. On physical examination, the child is well nourished …

BRAFV600E mutation in papillary thyroid microcarcinoma: a genotype–phenotype correlation

BRAFV600E mutation has emerged as a marker of aggressive behavior in papillary thyroid carcinoma but its significance in microcarcinoma is not entirely clear. One-hundred and twenty-nine papillary thyroid microcarcinomas were tested for BRAFV600E mutation by single-strand conformation polymorphism, and their clinicopathologic features (age, sex, tumor size, multifocality, nodal metastases, histologic subtype, tumor cell morphology, architecture, tumor-associated stromal reaction, tumor interface to non-neoplastic thyroid (well circumscribed vs infiltrative), extrathyroidal extension, lymphovascular invasion, intratumoral multinucleated giant cells, and adjacent non-neoplastic thyroid pathology) were examined. Compared with tumors without the mutation (39/129, 30%), the mutated microcarcinomas (90/129, 70%) showed significantly higher prevalence of infiltrative tumor borders (78/90 vs 23/39, P=0.001), tumor-associated stromal desmoplasia/fibrosis and/or sclerosis (80/90 vs 25/39, P=0.002), classic nuclear features of papillary thyroid carcinoma (90/90 vs 35/39, P=0.008) and cystic change (43/90 vs 11/39, P=0.05). BRAFV600E mutation was more frequent in classic (75%), tall cell (91%), and other variants (>70%) than in follicular variant (21%) of papillary thyroid microcarcinoma. Tumors without the mutation were significantly more likely to be solid, well circumscribed, and lacked desmoplasia/fibrosis or sclerosis. However, on multivariate analysis, only the follicular variant of papillary microcarcinoma was significantly associated with the absence of mutation (odds ratio (95% confidence interval): 0.09 (0.01–0.54)). Lymph node metastases (n=24) were more frequent in microcarcinomas with mutation than without (21/24 vs 3/24, P=0.02). All patients with lateral cervical node metastasis (n=9), and all but one tumor with extrathyroidal extension (n=17/18) showed BRAFV600E mutation. No significant differences were noted in age, sex, tumor size, multifocality, lymphovascular invasion, psammoma bodies, stromal calcification, intratumoral multinucleated osteoclastic-type giant cells, and lymphocytic infiltration between the two groups of tumors. BRAFV600E mutation is an early event in thyroid carcinogenesis, and is associated with distinctive morphology and aggressive features even in papillary thyroid microcarcinomas.