Annals of Diagnostic Pathology - Articles in Press

Are elastic stain and specialty sign out necessary to evaluate pleural invasion in lung cancers? - Corrected Proof

Geunyoung Jung, Hee Sang Hwang, Se Jin Jang, Jae Y. Ro — 2012-01-06

Abstract: The seventh edition of American Joint Committee on Cancer (AJCC) staging system assigns lung cancers with visceral pleural invasion in the tumor size of 3 cm or less than 3 cm as T2 and without pleural invasion as T1. However, it may be difficult to distinguish with certainty between PL0 (no pleural invasion) and PL1 (extends through the elastic layer) on routine hematoxylin and eosin (H&E) stain. In this study, 25 cases of peripherally located lung adenocarcinoma were retrieved from the surgical pathology archives at the Asan Medical Center from May through June 2009. One representative H&E-stained slide was selected from each case and circulated to 31 pathology trainees and board-certified pathologists at Asan Medical Center who evaluated presence or absence of pleural invasion on H&E-stained slides. Elastic stain was used to determine the final status of pleural invasion for each case. The concordance rate of all pathologists with elastic stain results was, overall, 60.5%. The concordance rate of 2 lung specialists was 64%, better than the remaining faculty (54.7%). Fellows' and residents' evaluations were slightly more concordant than those of faculty responses (faculty overall, 56.4%; fellows, 62%; residents, 63.6%), but this difference was not statistically significant (P = .228). Our results confirm that pleural invasion status is difficult to discern with certainty on H&E-stained sections alone. Therefore, we recommend the routine use of elastic stain in evaluation of pleural invasion in all peripherally located lung cancers. Furthermore, our study indicates that subspecialty sign out may be preferable in evaluation of pleural invasion status.

Microcalcifications of the breast: a mammographic-histologic correlation study using a newly designed Path/Rad Tissue Tray - Corrected Proof

2012-01-06

Abstract: The introduction of screening mammography has brought about a greater knowledge of early breast cancer characteristics. These improvements have led to a reduction in size of suspicious lesions and a shift from surgical to image-guided core needle biopsies (CNBs). Establishing correlation between histologic and imaging findings is required for accurate diagnosis. Currently, there are no standardized multidisciplinary protocols for evaluating such lesions. We correlated histologic and radiologic findings in mammographically detectable calcified lesions in CNBs using specially designed Path/Rad Tissue Trays (patent pending, University of Kansas). Evidence of calcification was analyzed in 440 with and without the use of tissue trays. After mammographic identification of the lesion, CNBs are harvested, placed in tissue trays, and x-rayed to confirm sampling of the lesion. Images of CNBs with calcifications are marked by the radiologists and sent to the pathologist along with the biopsies. Trays with CNBs are then placed into cassettes and sent to the laboratory where they are embedded without disturbing orientation. Identification and localization of targeted microcalcifications were accomplished by radiologists and pathologists in 68 of 71 cases when using the tissue trays compared with 292 of 369 without tissue trays. Confirmation of microcalcifications was accomplished after deeper sectioning into tissue blocks from discordant cases. In conclusion, a systematic approach is recommended to standardize reporting of calcifications. The use of Path/Rad Tissue Trays has created a level of concordance between pathologists and radiologists that previously did no exist. It improved diagnostic reliability, encouraged communication between pathologists and radiologists, and minimized false diagnoses and/or delays in cancer diagnosis.

Desmosomal proteins and microRNAs—markers for hybrid tumors (verrucous carcinoma with foci of squamous cell carcinoma) - Corrected Proof

Katarina Odar, Nina Gale, Nina Zidar — 2012-01-06

We read with interest the article by Terada , entitled “Verrucous carcinoma of the skin: a report on 5 Japanese cases.” The author reported on pathohistologic and immunohistochemical features in 5 cases of verrucous carcinoma (VC) of the skin. He described the downward infiltrative growth of atypical squamous epithelium at the tumor base in 2 cases of VC, which he termed “microinvasion,” and the coexistence with a focus of less-differentiated conventional squamous cell carcinoma (SCC) in 1 case. He concluded that there is lack of consensus on the nomenclature of the lesions that histologically exhibit features of VC coexisting with conventional SCC.

Low local metastatic rate may widen indication of nephron-sparing surgery for renal cell carcinoma - Corrected Proof

Zu-quan Xiong, Jie Zheng, Chen-chen Feng, Yun Bao, Qiang Ding, Zu-jun Fang — 2012-01-03

Abstract: To explore the rationale for renal-sparing surgery as an alternative method to radical nephrectomy in the treatment of renal cell carcinoma (RCC), we analyzed clinical data from 94 patients diagnosed as having RCC. They were divided into 3 groups based on the maximum diameter of their tumor specimens. Group A had tumors size ranging from 0 to 4 cm, group B had tumors size ranging from 4 to 7 cm, and group C had tumors size greater than 7 cm. Tissue samples (5 cm) were taken from the upper pole side, lower pole side, and renal pelvic side of the tumor pseudocapsule; if the tumor was located on 1 pole of the kidney, samples were collected from 2 directions. The specimens were then embedded in paraffin and cut serially at segments 0 to 1, 1 to 3, and 3 to 5 cm. Staining with hematoxylin and eosin, anti-pancytokeratin, and vimentin was performed to determine tumor type and tumor infiltration. From the 94 patients analyzed, 2 patients in group A had RCC metastasis within 1 cm of tissue around the pseudocapsule, and 4 patients in groups B and C had lymph node metastasis without metastasis in the tissue 1 cm outside the pseudocapsule in all 3 directions described. There was no statistical significant difference found between the incidence of local metastasis of the various tumor sizes, suggesting that local metastasis of RCC is not associated with the size of the tumor. Based on the observation that incidences of local metastasis were low in early-stage RCC, we came to the conclusion that pseudocapsule of RCC tumor might have growth-limiting effect on the tumor enclosed. It is theoretically a safer and better surgical option for patients with RCC with a smaller size of tumor and indications for radical nephrectomy to undergo renal-sparing surgery with an excision margin of 1 cm of normal tissue around the pseudocapsule of the tumor.

The evaluation of SOX9 expression and its relationship with carcinoembryonic antigen-related cell adhesion molecule 1 in gastric neoplastic and nonneoplastic lesions - Corrected Proof

2012-01-03

Abstract: The aims of this study were to investigate the expression of SOX9 (sex determining region Y [SRY]-related high-mobility group box 9) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in benign, premalignant, and malignant gastric lesions and to explore the association between SOX9 and CEACAM1 in gastric carcinogenesis. SOX9 and CEACAM1 expression was detected in normal gastric mucosa, hyperplastic polyp, intestinal metaplasia, gastric intraepithelial neoplasia, and adenocarcinoma by immunohistochemistry. There was low expression of SOX9 and no CEACAM1 expression in normal gastric mucosa and hyperplastic polyps. Intestinal metaplasia began to express CEACAM1 and showed more membranous staining of CEACAM1 than normal mucosa and hyperplastic polyps (P = .000), but SOX9 expression had no significant difference, and the coexpression of SOX9 and CEACAM1 ascended; therefore, the difference was significant (P = .000). Gastric intraepithelial neoplasia showed more SOX9 expression, coexpression of SOX9, and CEACAM1 than in intestinal metaplasia (P = .014 and P = .026, respectively). Carcinoma showed more cytoplasmic CEACAM1 (P = .010), more SOX9 expression (P = .001), and more their coexpression (P = .023) than gastric intraepithelial neoplasia. As to the histologic classification, poorly differentiated carcinoma showed more cytoplasmic CEACAM1 than well and moderately differentiated carcinoma (P = .006 and P = .024, respectively). In the Laurén classification, diffuse carcinoma showed more cytoplasmic CEACAM1 than intestinal carcinoma (P = .0035), but the SOX9 expression and their coexpresison showed no difference (P = .065 and P = .074, respectively). With the elevation of SOX9 expression and the changing of CEACAM1 expression patterns, the coexpressions of SOX9 and CEACAM1 were highly elevated from benign proliferative lesions to malignant lesions. Moreover, the SOX9 expression and the coexpression with CEACAM1 were correlated positively (r = 0.310; P = .015). In addition, SOX9 expression was positively correlated with CEACAM1 expression patterns (r = 0.124; P = .032). In addition, CEACAM1 expression patterns and coexpression of SOX9 and CEACAM1 show significant difference between T1 and T2 and T3 and T4 (P = .021 and P = .011, respectively). Accordingly, compared with N0, N2 and N3 showed significant difference in SOX9 expression (P = .018), CEACAM1 expression patterns (P = .010), and their coexpression (P = .010). SOX9 expression significantly increased from nonneoplastic lesions to neoplastic lesions, and CEACAM1 expression patterns markedly changed; their coexpression also showed signally elevated suggesting that SOX9, as a transcriptional regulator, play important roles in the changing of CEACAM1 expression patterns, which might promote the tumor progression.

Is p16 immunohistochemistry a more cost-effective method for identification of human papilloma virus–associated head and neck squamous cell carcinoma? - Corrected Proof

Jaiyeola Thomas, Thad Primeaux — 2011-12-26

Abstract: Tobacco and alcohol use are established risk factors for head and neck squamous cell carcinoma (HNSCC). However, patients with a unique subset of human papilloma virus (HPV)–associated HNSCC have been documented to have a better survival outcome. These tumors occur more frequently in the tonsils and oropharyngeal sites, among younger patients, higher socioeconomic group, and those exposed to more sexual partners and oral sex compared with HPV-negative HNSCC. Although tobacco- and alcohol-related HNSCCs appear to be on the decline, tonsillar and oropharyngeal HPV-associated tumors seem to be on the rise, and their prevalence varies widely in published reports, ranging from 20% to 60%. Human papilloma virus detection methods in tumor tissue vary and include polymerase chain reaction, in situ hybridization (ISH) technique for HPV DNA, and E6/E7 messenger RNA, with p16 immunohistochemistry (IHC) as a surrogate marker. The sensitivity and specificity of the different methods used are likely contributory factors to this wide variation. This study compares the p16 IHC staining patterns in HNSCC and laryngeal papillomas and assesses the concordance of p16 and high-risk HPV-ISH to determine the usefulness of p16 as a first-line marker. Using an objective criterion of diffuse intense confluent staining pattern as definite positive (akin to the 3+ of HER2/neu in breast cancer) and focal scattered staining pattern as equivocal reaction requiring confirmatory HPV assay, p16 IHC expression shows good concordance with high-risk HPV-ISH and can be used as a first-line marker. We propose p16 overexpression as a suitable surrogate and screening marker, with high potential of impacting the standard of care.

Deceiving high-grade cervical dysplasias identified as human papillomavirus non-16 and non-18 types by Invader human papillomavirus assays - Corrected Proof

Sumire Kitahara, Raymond C. Chan, W. Stephen Nichols, Elvio G. Silva — 2011-12-26

Abstract: High-grade cervical intraepithelial lesions (HGCINs) are easily diagnosed by established histologic criteria. However, we encountered problematic cases that are difficult to diagnose because features intermediate between dysplasia and metaplasia are present. p16 and Ki-67 immunostains proved HGCIN in these difficult and unusual cases. Because these are unusual cases of cervical dysplasia, we decided to type the human papillomavirus (HPV) using the Invader HPV test with analyte-specific reagents developed by Third Wave Technologies (Madison, WI, USA) (a new HPV screening assay applicable to tissue and amenable to rapid, sensitive, and specific detection of 14 high- to intermediate-risk HPV types) and a panel of immunostains. Results of these difficult cases are compared with classic HGCIN cases. We searched our pathology files over a period of 16 months for high-grade squamous intraepithelial lesion, cervical intraepithelial neoplasia II, cervical intraepithelial neoplasia III, and p16. To identify cases of difficult HGCIN with features intermediate between dysplasia and metaplasia, we reviewed all surgical cases of HGCIN that required p16 and Ki-67 diagnosis confirmation. Cases of interest were also stained with ProExC. Human papillomavirus screening and HPV 16/18 typing were performed by the Invader assays as described previously. Ten cases of classic HGCIN were easily diagnosed by hypercellularity, significant atypia, mitotic figures, and diffuse staining by p16, Ki67 and ProExC. The Invader assay identified HPV 16 (A9 positive/HPV16 positive) in 7 of 10 cases; the 3 others were A7 positive/not HPV18 (1) and A9 positive/not HPV16 (2). Eight cases of difficult HGCIN were identified. These showed only mild-to-moderate cellularity, a lack of significant atypia, absent-to-rare mitotic figures, and diffuse staining by p16, Ki-67, and ProExC. Human papillomavirus DNA was detected in 5 of 8 cases: only 1 was A9 positive/HPV16 positive, 1 was A5/A6 positive, 1 was A7 positive/not HPV18, and 2 were A9 positive/not HPV16. Three remaining cases demonstrated sufficient DNA to be analyzed by the Invader assay, but results were negative. This is a poorly recognized unusual group of cervical HGCIN with features intermediate between dysplasia and metaplasia that is easily confused by histologic examination. Immunostains prove the high-grade nature of these lesions, and Invader assay demonstrates association with HPV types other than 16/18 (ie, other HPV types detected by Invader assay). In this study, we present an unusual group of cases of high-grade dysplasia, not recognized by hematoxylin and eosin but identified by Ki67 and P16. It is very important to emphasize that this unusual group of high-grade dysplasias is associated with high-risk HPV but with types other than 16/18.

Detection of PAX3/PAX7-FKHR fusion transcripts in rhabdomyosarcoma and other small round cell tumors by 1-step reverse transcriptase polymerase chain reaction: a novel tool for diagnosis and differentiation - Corrected Proof

Xiu-Li Yang, Shu-Cheng Zhang, Shi-Wei Zhang, Hao Wang — 2011-12-26

Abstract: Rhabdomyosarcoma (RMS) is one of the most frequent soft tissue sarcomas in children. It is sometimes difficult to distinguish it from other small round cell tumors (SRCTs) depending on microscopic observations; although their treatment and prognosis varied widely, the same happens between alveolar RMS (ARMS) and embryonal RMS (ERMS). The role of PAX3/PAX7-FKHR fusion gene has been reported in ARMS but not in ERMS and SRCT. The aim of this study was to explore its value in RMS diagnosis and differentiation. Ninety-eight patients with ARMS (n = 13), ERMS (n = 25), pleomorphic RMS (n = 5), Ewing sarcoma (n = 11), neuroblastoma (n = 18), lymphoma (n = 24), and uncertain SRCT (n = 2) were analyzed. One hundred fifteen RNA samples were extracted from the primary tumor tissue at initial presentation and relapse. One-step reverse transcriptase polymerase chain reaction assays for the PAX3/PAX7-FKHR fusion transcripts were performed. Molecular findings were compared with original histologic diagnoses. PAX3-FKHR fusion transcript was detected in 9 ARMS samples, PAX7-FKHR fusion transcript was detected in 7 ARMS samples, and 2 uncertain SRCTs were detected; none of them were detected in ERMS, Ewing sarcoma, neuroblastoma, and lymphoma. Direct sequencing of PAX3 coding regions revealed a heterozygous mutation A→G (nt1380) at codon 448 (AAT→GAT), resulting in substitution of Asn-448 for Asp. Detection of PAX3/PAX7-FKHR fusion transcripts by 1-step reverse transcriptase polymerase chain reaction is a novel tool for RMS diagnosis and differentiation.

Absence of IDH1-R132H mutation predicts rapid progression of nonenhancing diffuse glioma in older adults - Corrected Proof

2011-12-26

Abstract: Advanced age and contrast enhancement portend a poor prognosis in diffuse glioma (DG). Diffuse glioma may present as nonenhancing tumors that rapidly progress in weeks to months to a pattern of ring enhancement, characteristic of glioblastoma (GBM). Mutations involving isocitrate dehydrogenase 1 (IDH1) have recently emerged as important diagnostic and prognostic markers in DG. R132H is the most common mutation, expressed in more than 80% of DG and secondary GBM but in less than 10% of primary GBM. Adults older than 50 years with nonenhancing, rapidly progressing DG were identified. A comparison group comprised randomly selected, age-matched patients with nonenhancing, nonprogressing DG. Isocitrate dehydrogenase 1 status was evaluated using anti–IDH1-R132H antibodies (Dianova, Hamburg, Germany). The results were correlated with the clinical outcomes. We identified 4 patients who presented with nonenhancing DG that rapidly progressed to ring-enhancing lesions that were subsequently diagnosed on surgical resection as GBM. This group showed absent IDH1-R132H expression, which is characteristic of primary GBM. The comparison group of 5 patients presented with nonenhancing, nonprogressing DG, and all 5 tumors showed IDH1-R132H expression. In conclusion, negative IDH1-R132H mutation status in nonenhancing DG of older adults is a poor prognostic factor associated with rapid progression to ring-enhancing GBM. The shorter interval of progression and negative IDH1-R132H mutation status suggest a similar molecular pathway as seen in primary GBM.

Significance of Ki-67 and p53 immunoexpression in the differential diagnosis of oral necrotizing sialometaplasia and squamous cell carcinoma - Corrected Proof

Tahereh Dadfarnia, Bassim S. Mohammed, Mahmoud A. Eltorky — 2011-12-26

Abstract: Necrotizing sialometaplasia (NS) is a benign condition that usually involves the hard palate and can be mistaken for invasive squamous cell carcinoma (SCC). In this study, we have demonstrated that p53 and Ki-67 staining may assist in the differential diagnosis of NS from SCC. Thirteen cases of NS and 20 cases of oral cavity SCC were randomly selected from our surgical pathology archive from 1992 to 2009. Each case was additionally stained with Ki-67, p53, BCL-2, p16, and epidermal growth factor receptor (EGFR) antibodies. All 13 cases of NS were negatively stained for BCL-2, EGFR, and Ki-67. Three cases (23%) showed weak and focal positive nuclear staining for p53. Two cases (15%) showed positive staining for p16. In 16 well-differentiated SCC cases, p53 was positive in 12 cases (75%); BCL-2, p16, EGFR were positive in 3 cases (18%); and Ki-67 was positive in all cases (100%). In 4 moderately differentiated SCC cases, p53 expression was positive in all cases. Two tumors (50%) had a positive expression of BCL-2. Three cases (75%) had a positive p16 staining, and 1 (25%) had a positive EGFR staining. All cases were positive with high nuclear staining greater than 35% of cells for Ki-67. Ki-67 and p53 showed more intense staining and increased in moderately differentiated SCC comparing with well-differentiated SCC and NS. BCL-2, EGFR, and p16 had the same pattern of staining with the same extent in NS and SCCs. The diagnosis of NS may be difficult and may be supplemented via immunohistochemistry by demonstrating focal or absent p53, low to absent Ki-67 (<10% of cells). Although Ki-67 and p53 staining are generally more intense and are increased in malignancy, these findings may be helpful adjuncts in the differential diagnosis of NS from SCC in appropriate clinical setting.

Up-regulation of Notch-1 in psoriasis: an immunohistochemical study - Corrected Proof

Asmaa Gaber Abdou, Alaa Hassan Maraee, Amany Sharaf, Nada Farag Elnaidany — 2011-12-26

Abstract: The Notch pathway plays a key role in differentiation, proliferation, and influencing cell fate decision in multiple organisms and tissues including the epidermis and its appendages. The role of Notch-1 in psoriasis has not been widely evaluated; therefore, the current study aimed to evaluate its role in etiopathogenesis of this common skin disease. The current study used immunohistochemical technique to evaluate Notch-1 expression in 35 lesional biopsies of patients having chronic plaque psoriasis in comparison with normal skin biopsies, representing the control group. Notch-1 was expressed in the epidermis of both normal and psoriatic skins; however, the intensity was in favor of psoriatic lesion, and the nuclear form of Notch-1 was more frequently and diffusely seen in psoriasis. Exacerbation of psoriasis as assessed by the Psoriasis Area and Severity Index score was significantly associated with intense (P = .005) and nuclear form of Notch-1 expression (P = .0001). The nuclear form of Notch-1 was also correlated with female sex (P = .043). From this study, up-regulation and not down-regulation of Notch-1 may have a role in pathogenesis of psoriasis. The nuclear form is responsible for the exacerbation of symptoms, and it is the one that may disappear by the effect of psoralen and ultraviolet A radiation (PUVA) therapy.

Clinicopathologic and biomarker analysis of invasive pleomorphic lobular carcinoma as compared with invasive classic lobular carcinoma: an experience in our institution and review of the literature - Corrected Proof

Melissa Jacobs, Fang Fan, Ossama Tawfik — 2011-12-26

Abstract: Pleomorphic lobular carcinoma (PLC) is a distinct morphological variant of invasive lobular carcinoma (ILC). Although PLC retains the distinctive loosely cohesive and single-file growth pattern of ILC, it has specific distinguishable characteristics, including enlarged nuclei with greater nuclear irregularity, increased hyperchromasia, prominent nucleoli, increased mitotic activity, and abundant eosinophilic cytoplasm. We compared the clinicopathologic features and biomarker expression of PLC and ILC. Fifty-eight cases of classic ILC (5.3%) and 7 cases of PLC (0.6%) were identified from our file between January 2002 and December 2010. Histopathologic data and tumor biomarkers were recorded. Clinical follow-up information (3-93 months; median, 29 months) for distant metastasis and survival was also gathered. Fisher exact test was used, and results were considered statistically significant if P value is less than .05. Our results showed that compared with classic ILC, PLC was more frequently grade III (P < .01), estrogen receptor negative (P < .001), and has Ki-67 greater than 10% (P < .002). In conclusion, PLC is more frequently higher grade and may exhibit an adverse biomarker profile (negative estrogen receptor and high Ki-67) as compared with classic ILC. However, no significant differences were found between PLC and classic ILC for axillary lymph node/distant metastases and survival.

Squamous cell carcinoma of the renal pelvis - Corrected Proof

Feriyl Bhaijee — 2011-12-22

Abstract: Primary squamous cell carcinoma (SCC) of the renal pelvis is rare because SCC represents only 0.5% to 0.8% of malignant renal tumors. Chronic irritation, inflammation, and infection induce squamous metaplasia of the renal collecting system, which may progress to dysplasia and carcinoma in most of affected individuals. Nephrolithiasis, especially formation of staghorn calculi, is the most common risk factor for SCC, which usually occurs in older adults (age 50-70 years) with no sex predilection. Clinical features include flank or abdominal mass, weight loss, hematuria, or paraneoplastic syndromes, such as hypercalcemia. Radiologically, SCC of the renal pelvis may appear as a solid mass, hydronephrosis, or calcifications. The radiologic differential diagnosis includes primary and secondary renal neoplasms and xanthogranulomatous pyelonephritis. Squamous cell carcinomas of the renal pelvis are usually large, necrotic, and ulcerated, with gross invasion of the renal parenchyma and perinephric soft tissue. Most SCCs of the renal pelvis are moderately or poorly differentiated and typically present at an advanced stage. Surgical resection and adjuvant chemoradiotherapy are rarely curative. The prognosis is dismal with a 5-year survival rate of less than 10%.

Spindle epithelial tumor with thymus-like differentiation of the thyroid (SETTLE): Report of two cases (one associated with a parathyroid adenoma) - Corrected Proof

2011-12-09

Abstract: Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare tumor usually localized in the thyroid gland and perithyroid tissues. It is considered to arise from ectopic thymic tissue or branchial pouch remnants. It occurs more frequently in children and adolescents. We report 2 cases of spindle epithelial tumor with thymus-like differentiation localized in the thyroid gland, and 1 of them was associated with a parathyroid adenoma. We emphasize the need for a close and long-term follow-up in these patients.

Giant cystic superficial low-grade fibromyxoid sarcoma - Corrected Proof

Dimitrije Brasanac, Natasa Sulovic Dzelatovic, Martina Stojanovic — 2011-12-02

Abstract: Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of fibrosarcoma characterized by combination of myxoid and fibrous zones consisted of bland spindled cells. Despite its innocuous histopathologic appearance, LGFMS can produce local recurrence and distant metastasis in the significant number of cases. Tumors are usually situated in deep soft tissues, whereas superficial localization in the dermis and subcutaneous fat is rare. We present a case of 56-year-old man with the huge tumor on the lateral part of the right buttock that had been slowly enlarging over the previous 15 years. Needle aspiration cytology provided only serohemorrhagic fluid with the red blood cells and rare inflammatory elements. Complete surgical excision revealed subcutaneous tumor, measuring 220 × 180 × 130 mm, which was completely cystic, with the residual tumor tissue in the 3- to 25-mm-thick wall. Histopathologic, immunohistochemical, and cytogenetic analysis confirmed LGFMS diagnosis. Long evolution, large size, and the superficial location could cause the repetitive tissue damage and hemorrhage, eventually transforming the tumor into a large cystic mass. In some parts, collagen rosettes composed of eosinophilic core surrounded by a palisade of tumor cells could be seen, occasionally appearing to sprout from the perivascular fibrous coat. Data from the literature regarding cystic appearance as well as the superficial location and the size of LGFMS in relation to the clinical outcome are presented and discussed.

Processing radical prostatectomies: an alternate-slice method is comparable with total embedding - Corrected Proof

Cesar A. Llanos, Clifford Blieden, Stephen E. Vernon — 2011-11-24

Abstract: Receipt of radical prostatectomy specimens in the histopathology laboratory is quite common in academic centers and community hospitals. Despite numerous processing protocols, there is not an accepted standard method of processing. There are potential disadvantages of total sampling of the prostate; however, other alternatives have not been proven to show significant advantages. We present a partial sampling method (alternate slice) and compare its results to the total embedding method. Consecutive radical prostatectomy specimens were selected to compare both histologic sampling methods. The primary method of sampling was total embedding. Subsequently, alternate slice sections from the anterior, middle, and posterior thirds of the gland were reviewed. Seminal vesicle, bladder neck, and margins were similarly evaluated in both methods. Total sampling resulted in an average of 30 blocks compared with 18 in the alternate slice method. Gleason correlation was 87.5%; extraprostatic extension correlation was 97.9%. There was complete correlation in margin status and perineural invasion. Pathologic staging correlation was 97.9%. In summary, this alternate slice method compares very favorably with the total embedding method.

The value of endocervical curettage after conization for cervical intraepithelial neoplasia - Corrected Proof

2011-11-24

Abstract: The objective of this study is to assess the value of postcone endocervical curettage, after conization of cervical intraepithelial neoplasia or carcinoma as a predictive tool for residual lesions. This is a retrospective observational study. All data were obtained by the University Hospital of Zurich, Department of Gynaecology. One hundred fifty patients underwent hysterectomy within 12 months after conization and endocervical curettage from 1993 to 2006. To analyze the sensitivity, specificity, and the positive predictive value (PPV) and negative predictive value (NPV) of the endocervical curettage after conization, we used the Fisher exact test and χ2 test. The main outcome measures are the sensitivity and specificity as well as the PPV and NPV of the postconization endocervical curettage. The endocervical curettage exhibited a sensitivity of 0.38, a specificity of 0.85, a PPV of 0.56, and an NPV of 0.73. Comparing patients younger than 50 years to women 50 years or older, endocervical curettage had a sensitivity of 0.35 and 0.44, a specificity of 0.83 and 0.94, a PPV of 0.46 and 0.88, and an NPV of 0.76 and 0.63, respectively. The endocervical curettage after conization of cervical intraepithelial neoplasia does not generally improve the prediction of residual lesions. However, in women 50 years or older, a higher specificity and PPV, 0.94 and 0.88, respectively, was observed. Therefore, this subgroup of patients may benefit from an endocervical curettage.

Two cases of endobronchial carcinoid masked by superimposed aspergillosis: a review of the literature of primary lung cancers associated with Aspergillus - Corrected Proof

John Robert Nilsson, Carlos S. Restrepo, Jaishree Jagirdar — 2011-11-14

Abstract: We describe 2 cases of endobronchial pulmonary carcinoid tumor with superimposed Aspergillus colonization. The Aspergillus hyphae were associated with fibrin, ulcer debris, and granulomatous inflammation in part masking the carcinoid tumor. Presence of necrotic debris made diagnosis on biopsy difficult, and atypical carcinoid could not be ruled out. The association of carcinoid tumor with aspergillosis is rare and has been reported in 4 other cases thus far. A review of the literature reveals at least 35 cases of lung carcinoma with coexisting Aspergillus upon presentation. Most of these carcinomas are either cavitary squamous cell or adenocarcinomas harboring an aspergilloma. The other carcinomas are associated with bronchial obstruction as in carcinoids or are a minor component of a preexisting cavity raising the possibility of “scar carcinoma.” As in aspergillomas not associated with carcinoma, upper lobe involvement predominates. Diagnosis can be challenging with delayed discovery of underlying neoplasm leading to suboptimal treatment.

Oncocytoma of the adrenal gland medulla - Corrected Proof

Marcela Chisté, Robert J. Poppiti, Fernando J. Bianco — 2011-11-07

Abstract: We report an unprecedented case of an oncocytoma of the adrenal gland medulla in a 61-year-old woman. The patient presented with right flank pain and hematuria. Computed tomographic studies revealed a right adrenal gland mass that measured 2 cm, which was subsequently excised laparoscopically. Grossly, the tumor in the medulla measured 1.9 × 1.2 cm, weighed 5 g, and had a solid tan-brown cut surface. Histologically, it consisted of large tumor cells containing eosinophilic granular cytoplasm arranged in trabecular and nodular patterns. Electron microscopy revealed closely packed mitochondria in the cytoplasm of almost all tumor cells. The tumor cells were immunohistochemically positive for vimentin. The patient resumed usual activities 2 weeks after surgery, and at 6-month follow-up, she is doing well.

Application of the British National Health Service Breast Cancer Screening Programme classification in 226 breast core needle biopsies: correlation with resected specimens - Corrected Proof

2011-11-07

Abstract: A retrospective study correlating the diagnosis made on core needle breast biopsy (CNB) with the diagnosis made on the final surgical specimen was done using the British National Health Service Breast Cancer Screening Programme (NHSBSP) classification for CNB on 226 patients during a period of 15 months. Statistical analysis was used to evaluate sensitivity, specificity, and positive and negative predictive values of the NHSBSP diagnostic categories. Cohen κ was used to evaluate the agreement between the diagnosis on CNB and the final pathologic diagnosis in “clinically positive cases.” Finally, a comparative analysis between the CNB method and fine needle aspiration biopsy was made. The distribution of our cases for each diagnostic category reflects the literature guidelines, with minor differences in the B2 and B4 groups. Statistical data about the patients' follow-up revealed a small number of false-negative cases in the B1 and B2 categories and no false-positive cases in the B4 and B5 groups. Uncertain malignant lesions (B3 category) were divided into 3 major areas (papillary lesions, fibroepithelial proliferations with cellular stroma, and intraepithelial atypical lesions such as ductal intraepithelial neoplasia grade 1/lobular intraepithelial neoplasia grade 1). Of the 29 patients in the B3 category, 26 underwent surgery. Cohen κ analysis showed a strong statistical correlation (κ = 0.77; Z = 4.3; significance >1.96; α = .05) between CNB diagnosis and surgical pathology final results in the subgroup of high-risk patients (diagnosis, ≥ductal intraepithelial neoplasia grade 1 on CNB). Global diagnostic power of CNB in all 226 cases revealed high sensitivity (88.3%) and slightly lower specificity (72.8%). In 42 “doubtful” cases, synchronous fine needle aspiration biopsy and CNB were performed, showing a complementary role in the diagnostic phase of breast lesions. Core needle breast biopsy represents the criterion standard method in the diagnostic phase of many breast tumors; the NHSBSP classification is a useful reporting system that provides a good standardization of the pathologic diagnosis and provides a clear guideline for the correct management of the patient.

Aggressive meningiomas involving the parotid gland - Corrected Proof

Kelly H. Joggerst, Lauren A. Langford, Michelle D. Williams — 2011-11-07

Abstract: Parotid masses remain challenging secondary to the great diversity of primary tumors that may arise in the salivary glands and propensity for regional and even distant metastases to occur in this region. Meningioma must also be considered in the differential diagnosis of parotid masses, whether from direct extension, metastases, or as an extracranial primary. We herein report 4 cases of aggressive meningioma involving the parotid gland and the pathologic considerations in evaluating these tumors.

Abnormal granulation of blood granulocytes in mucopolysaccharidosis VI—a case report - Corrected Proof

2011-11-07

Abstract: Mucopolysaccharidosis (MPS) is a group of lysosomal storage disorders in which there is deficiency of specific enzymes. Depending upon the enzyme which is deficient and the nature of the material that accumulates at various tissues, the MPS is divided into 8 types (MPS I to MPS VIII). In MPS VI, deficiency of aryl B sulfatase leads to the accumulation of dermatan sulfate. Mucopolysaccharidosis VI, also called as Maroteaux-Lamy syndrome, in its severe form presents with bony lesions, corneal clouding, hepatosplenomegaly, cardiovascular abnormalities, and central nervous system deterioration. This form of MPS features the most striking abnormal granulation in the circulating white blood cells. Mucopolysaccharidosis VI has an estimated global incidence of 1 in 340 000. The number of cases showing abnormal granules in the cytoplasm of leucocytes is still rarer. We report a case of MPS VI with abnormal granules in the circulating blood leukocytes.

α-Fetoprotein–producing ovarian tumor in a postmenopausal woman with germ cell differentiation - Corrected Proof

Shiori Meguro, Masanori Yasuda — 2011-11-07

Abstract: α-Fetoprotein (AFP)–producing ovarian tumors (APOTs) are rarely encountered in postmenopausal women, irrespective of whether they are of the germ cell or non–germ cell type. The APOTs that do occur in postmenopausal women are characterized by variable histologies such as hepatoid carcinoma, yolk sac tumor, and epithelial malignancies, most of which are combined. We herein present a case with APOT, which arose in a 58-year-old, gravida 2, para 2, postmenopausal woman. Preoperatively, the tumor, which was in the right ovary, was found to produce AFP (102768.0 ng/mL). The tumor was evenly composed of glands mimicking secretory endometrial gland or fetal gut accompanied by abundant stroma. Immunohistochemically, these glands were positive for SALL4, glypican-3, and hepatocyte nuclear factor 1β. We considered the present case as an AFP-producing adenocarcinoma with adenofibroma showing germ cell differentiation, but it seemed controversial that this tumor should be designated as a yolk sac tumor of the glandular type. The expression profiles of SALL4, OCT4, glypican-3, and hepatocyte nuclear factor 1β were thought to provide interesting implications to characterize the present case.

Lipomatosis coli, a mimicker of familial polyposis - Corrected Proof

Neda Zarrin-Khameh, Eric M. Haas, Jae Ro, Michael J. Thrall — 2011-11-07

Abstract: Multiple intestinal lipomas (lipomatous polyposis) are quite rare, and they can be quite challenging to diagnose because this condition may be clinically confused with familial adenomatous polyposis with a suggestive family history. Herein, we present a case of lipomatous polyposis that was presented with abdominal pain and, in colonoscopy, had more than 100 polyps. The patient was admitted for surgery with diagnosis of familial polyposis. Resected colon specimen had multiple polyps ranging from 0.1 to 1.5 cm. Microscopically, the polyps were composed of mature adipose tissue with normal overlying mucosa. There were also increased fat cells in the submucosa of the colon adjacent to the polyps. Lipomatous polyposis rarely occurs and can be confused with familial polyposis. Polypectomy is a simple and cost-effective procedure to help in diagnosis and prevent a major surgery.

Sclerosing epithelioid fibrosarcoma of the pancreas - Corrected Proof

Shuting Bai, Nirag Jhala, N. Volkan Adsay, Shi Wei — 2011-11-07

Abstract: Sclerosing epithelioid fibrosarcoma (SEF) is a distinctive variant of fibrosarcoma characterized by epithelioid tumor cells arranged in nests, cords, or sheets embedded within a sclerotic collagenous matrix. It is a relatively newly described malignant fibroblastic tumor, with only fewer than 100 cases reported in English literature. Most cases are located in the lower extremities and limb girdles. Here, we present a case of SEF of the pancreas in a 67-year-old white man and provide a review of literature to date, with emphasis on the differential diagnosis. To our knowledge, this is the first reported case of SEF involving the pancreas.

Dentigerous cyst of inflammatory origin—a diagnostic dilemma - Corrected Proof

Ramandeep S. Narang, Adesh S. Manchanda, Preeti Arora, Kawar Randhawa — 2011-11-04

Abstract: Odontogenic cysts commonly encountered in dental practice are the radicular cysts and dentigerous cysts. Apart from the developmental origin of dentigerous cysts, an inflammatory origin has also been suggested. It has been reported that inflammation progressing from the root apex of the deciduous tooth brings about development of the dentigerous cyst around the unerupted permanent tooth. The aim of the present article is to report 4 additional cases of dentigerous cyst believed to be of inflammatory origin and to highlight the diagnostic dilemma in segregating both the entities. The 4 cases were of patients with a mixed dentition with the pathology related to the deciduous tooth present. Radiographically, pericoronal radiolucency was seen attached at the cementoenamel junction of impacted tooth and in continuation with lamina dura of deciduous tooth. Microscopically, the cystic cavity was lined by reduced enamel epithelium like lining, which was hyperplastic to anastomosing in areas in few cases. This study proposes the predicament in accurately diagnosing such cases.

Histology and distribution of prostatic tissue on prostatic urethral margins: evaluation of radical prostatectomy specimens and implications on frozen section analysis - Corrected Proof

Da Hye Son, Jae Y. Ro, Mun Jung Kang, Woo Young Jang, Yong Mee Cho — 2011-11-04

Abstract: The identification of prostate-specific antigen (PSA)–producing glands in prostatic urethral margins is often challenging, especially when examined as intraoperative frozen sections. To assess the histology of periurethral prostatic urethral glands and their expression of PSA and cytokeratins 7 and 20, we examined prostatic urethras of frozen and permanent sections of radical prostatectomy specimens. We observed 3 types of prostatic urethral glands: urethral mucosal, prostatic acinar, and mixed. The urethral mucosal type consisted of a single layer of surface cuboidal to columnar cells with densely eosinophilic luminal cytoplasm and underlying urothelial cells. The prostatic acinar type was lined by prostatic-type secretory cells and basal cells. The mixed type showed luminal secretory cells and underlying urothelial cells. The gland types were correctly assigned in most frozen section slides. The proximal segment of the prostatic urethra and the bladder neck consisted mostly of the urethral mucosal type, whereas the distal segment and apical margins consisted mostly of the prostatic acinar type. Prostate-specific antigen was expressed in secretory cells in prostatic acinar and mixed types, whereas cytokeratin 7 was expressed by urothelial cells and surface cells of the urethral mucosal type. Cytokeratin 20 was not expressed in any of these cells. These results indicate that PSA-expressing cells are abundant in the distal segment of the prostatic urethra and apical margin and share histologic features of prostatic secretory cells. These PSA-expressing prostatic acinar and mixed-type glands should be reported as a potential source of PSA-secreting benign glands.

Comparison of clarity of nucleocytoplasmic differentiation of oral tissues processed by microwave and conventional methods - Corrected Proof

Smitha Naik K., Shilpa Patel, Madhusudhan Astekar, Dinesh Rao — 2011-11-04

Abstract: The microwave-assisted tissue processing is believed to have brought a revolutionary improvement in histopathology. The technique shortens the tissue processing time from hours to minutes. The technique is responsive to the patient and physician needs, improves the use of reagents while reducing or eliminating their toxicity, creates a personnel-friendly workflow, and places the laboratory in a better position to meet the demands of the rapidly expanding field of molecular medicine. This study was conducted to determine the efficacy of microwave tissue processing method for orofacial biopsy specimens by comparing 5 different protocols of microwave histoprocessing with the conventional method, based on the clarity of nucleocytoplasmic differentiation of tissues processed by each method. The current study demonstrated that different protocols of microwave histoprocessing can be achieved without a demonstrable decrease in section quality or interpretation.

Metastatic endometrial endometrioid carcinoma with clear cell changes to the breast: a case report - Corrected Proof

Hanan Farghaly — 2011-11-02

Abstract: Metastasis to breast from extramammary tissue is rare, and endometrial cancer has rarely been reported to metastasize to the breast. An extensive search in the medical literature reveals only 2 cases. They can be easily mistaken for primary breast carcinoma both clinically and radiologically, even with known history of endometrial carcinoma. This report presents a case of a 64-year-old woman who had endometrial carcinoma treated with total hysterectomy and adjuvant radiation and chemotherapy. Three years after the diagnosis, she had evidence of a solitary breast metastasis. To our knowledge, this is the third described case of endometrial cancer metastatic to the breast and the first in which the endometrial carcinoma demonstrates significant clear cell changes. This report is a reminder that although rare, endometrial carcinoma has the potential to metastasize to breast and illustrates how metastatic lesions in the breast can masquerade clinically as a primary carcinoma. Furthermore, essential guidelines necessary to distinguish primary from metastatic lesions in the breast are presented.

Platelet satellitism and dual surface immunoglobulin light-chain expression in circulating splenic marginal zone lymphoma cells - Corrected Proof

2011-09-02

Abstract: Platelet satellitism is believed to be an in vitro phenomenon induced at room temperature in ethylenediamine tetraacetic acid–anticoagulated blood. Most reports involve neutrophils; involvement with circulating lymphoma cells are exceedingly rare. Normally, mature B cells exhibit allelic exclusion in which a single class of surface immunoglobulin light chains (either κ or λ) is expressed. The simultaneous expression of both κ and λ immunoglobulin light chains is rare. Herein, we report the unusual case of a patient with splenic marginal zone lymphoma in which circulating lymphoma cells express dual surface immunoglobulin light chains and exhibit platelet satellitism. In addition to clinical findings, a comprehensive analysis of the peripheral blood including correlated light and electron microscopy as well as flow cytometry are described.

Epithelioid schwannoma of soft tissue: unusual morphological variant causing a diagnostic dilemma - Corrected Proof

2011-08-17

Abstract: Epithelioid variant of peripheral nerve sheath tumors is a rare but, at the same time, a well-known entity especially in the malignant counterpart. However, peculiar epithelioid morphology in soft tissue schwannomas is unusual and has been defined recently. These tumors may cause diagnostic errors owing to their increased cellularity and epithelioid morphology. Typical histologic features of classic schwannoma such as Antoni A and B areas, Verocay bodies, and hyalinized vessels are either absent or only present in focal areas. Furthermore, strong and diffuse S-100 protein expression is seen in both benign and malignant counterparts of epithelioid schwannoma. The findings that are suggestive of the benign nature of the lesion are long-term clinical history, small size, superficial localization, encapsulation, bland morphology, lack of mitosis and necrosis, and a benign clinical course after complete excision. Pathologists should be aware of the epithelioid variant of schwannoma to avoid false diagnosis of malignancy. We hereby report 3 cases of unusual benign epithelioid schwannoma of the soft tissue with special regard to problems in differential diagnosis.

Crystal-storing histiocytosis: a rare lesion in periapical pathology - Corrected Proof

2011-08-17

Abstract: Crystal-storing histiocytosis is a rare manifestation of plasma cell dyscrasia/monoclonal gammopathies and lymphoproliferative disorders, characterized by cytoplasmic accumulation of crystallized immunoglobulins in histiocytes. Nevertheless, some reported cases of crystal-storing histiocytosis raise the possibility that this lesion may also be reactive. Crystal-storing histiocytosis in the oral cavity is extremely rare; only one case affecting the tongue has been reported in the English-language literature. In this report, we discuss the case of a 38-year-old man who presented a persistent periapical lesion affecting the maxillary left lateral incisor. Histopathological analysis showed numerous crystal-laden histiocytes associated with a mild plasma cell infiltrate within a fibrous stroma. The plasma cells failed to show clonal light-chain restriction, and the patient had no associated hematologic disorder or systemic disease. Thus, this lesion was probably the result of hypersecretion of immunoglobulins by polyclonal plasma cells found in the periapical lesion. Crystal-storing histiocytosis should be considered in the differential diagnosis of periapical lesions.

Colonic in situ mantle cell lymphoma - Corrected Proof

2011-08-16

Abstract: This report describes the first case, to our knowledge, of in situ mantle cell lymphoma (MCL) in the gastrointestinal tract identified retrospectively by immunostains and fluorescence in situ hybridization (FISH) analysis after progression to disseminated disease with pleomorphic morphology several years later. A 45-year-old man with blood per rectum underwent colonoscopy and had random biopsies interpreted as benign colonic mucosa. Two years later, he presented with ileocolic intussusception related to enlarged lymph nodes. Biopsies on the second presentation demonstrated widespread MCL. Reevaluation of the original colonic biopsies showed cyclin D1–positive cells within small lymphoid aggregates, confirmed by FISH for t(11;14). Postchemotherapy, lymphoid aggregates in colonic biopsies showed scattered cyclin D1– and FISH t(11;14)–positive cells, similar to the original in situ lymphoma. We discuss this case in the context of the current understanding of the evolution of MCL and the difficulties associated with detecting primary GI lymphoma.

A patient with prostate cancer and multiple myeloma—diagnostics and possible association of both diseases - Corrected Proof

2011-08-16

Abstract: In this report, we describe a case of a patient with prostate cancer and multiple myeloma as the second metachronous malignant disease. To our knowledge, synchronous occurrence of bone marrow prostate cancer metastases and multiple myeloma—as it was found in the clinical disease course of our patient—has not been documented in the literature. Among other diagnostic procedures, cytomorphology and immunocytochemistry analyses contribute to detection of metastases of epithelial cells and synchronous plasma cell proliferation in bone marrow. Occurrence of multiple myeloma and prostate cancer in our patient adds to other similar reports and points to possible association between both diseases and also to other factors involved in the development of a second malignant disease. Further studies are needed to confirm and clarify this association, because prostate cancer is a relatively common malignant disease.

Clinically aggressive primary solid pseudopapillary tumor of the ovary in a 45-year-old woman - Corrected Proof

2011-07-21

Abstract: We report the first case of primary solid pseudopapillary tumor of the ovary with aggressive behavior and fatal outcome in a 45-year-old woman. The patient presented with weight loss, decrease of appetite, and abdominal bloating for the last several weeks. Computed tomography scan revealed an ovarian mass, omental caking, complex ascites, and 2 hepatic lesions. The pancreas was unremarkable. Grossly, the ovarian mass showed severe capsular adhesion, and the cut surface was cystic and solid. On histologic examination, the tumor was composed of diffuse solid pseudopapillary and pseudocystic patterns. The neoplastic cells were uniform and round with very dispersed chromatin. The cytoplasm was faintly pink. There was mild atypia, but the mitotic rate was as high as 62 per 50 high-power field, and the Ki-67 was elevated at 20%. The tumor exhibited severe necrosis. Numerous foci of lymphovascular invasion were also seen. The tumor cells were positive for cytokeratin (focal) and for β-catenin (cytoplasmic and nuclear patterns). They were negative for chromogranin, synaptophysin, thyroglobulin, calcitonin, hepatocyte-paraffin 1, epithelial membrane antigen, calretinin, and α-inhibin. Electron microscopic study revealed nests of tumor cells with oval nuclei. The cytoplasm contained numerous pleomorphic mitochondria interspersed among short strands of rough endoplasmic reticulum. The tumor involved the fallopian tube, omentum, cul-de-sac, and abdominal wall. The pelvic washing was also positive for tumor cells. Despite chemotherapy, the patient's condition had worsened, and she died of her disease 8 months after the initial diagnosis. We discuss the differential diagnosis of this tumor and the hypothesis of its origin.

Primary mucinous adenocarcinoma of the larynx in female patient: a rare entity - Corrected Proof

Tastekin Ebru, Yalcin Ömer, Oz Puyan Fulya, Usta Ufuk, Kutlu Kemal — 2011-07-20

Abstract: Laryngeal malignant tumors are mainly composed of squamous cell carcinomas. Glandular carcinomas of the larynx are rare tumors that constitute less than 1% of all laryngeal malignancies where “adenocarcinoma not otherwise specified” is the most common histologic subtype. Here we report a case of a 70-year-old female patient with primary laryngeal mucinous adenocarcinoma. The rarity of the tumor type and the differential diagnosis of this tumor before reporting it as a primary adenocarcinoma of the larynx are discussed here with literature findings.

Molecularly confirmed primary malignant rhabdoid tumor of the urinary bladder: implications of accurate diagnosis - Corrected Proof

2011-07-20

Abstract: Malignant rhabdoid tumors (MRTs) are well recognized in the kidney and extrarenal sites such as soft tissues, retroperitoneum, and bladder but are classified as atypical teratoid/rhabdoid tumors in the central nervous system. The unifying features of both extracranial MRT and atypical teratoid/rhabdoid tumors are the exon deletions/mutations of the SMARCB1 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) gene in 22q11.23 and resulting loss of SMARCB1/INI1 (integrase interactor 1) protein expression by immunohistochemistry. We herein report a case of extrarenal rhabdoid tumor confined to the bladder in a 3-year-old child, diagnosed by histopathology and confirmed by immunohistochemical and molecular studies. This is only the fourth molecularly proven primary MRT of the bladder to be reported. The patient's peripheral blood was negative for the deletions observed in the tumor, thereby confirming a sporadic origin for the tumor. Given the possible dismal outcome, urgency for definitive diagnosis to institute intensive multimodality therapy, histopathologic differential diagnosis with rhabdomyosarcoma and urothelial carcinoma with rhabdoid features, and lack of consensus management guidelines, oncologists, urologists, and pathologists must be aware of this entity. Evaluation for a germ line SMARCB1 alteration may greatly aid risk stratification and family planning.

Proximal-type epithelioid sarcoma of the vulva with INI1 diagnostic utility - Corrected Proof

2011-07-04

Abstract: Proximal epithelioid sarcoma (PES) is an extremely uncommon neoplasm of the vulva with an aggressive behavior. Recently, these authors experienced a case of proximal-type ES in a 41-year-old woman who was admitted for a rapidly growing mass in the right mons pubis. An about-1-cm-sized mass was initially noticed one and a half years earlier. The excised mass, however, was 8 cm in greatest dimension and was relatively well circumscribed. The cut surface was trabeculated, with multifocal hemorrhages and necroses. Microscopically, the tumor consisted of epithelioid rhabdoid cells with vesicular nuclei, large prominent nucleoli, and cytoplasmic eosinophilic globules comparted by thin, fibrous septae. The main differential diagnoses included PES, other sarcomas with epithelioid cells, malignant melanoma, and sarcomatoid carcinoma. The tumor cells were diffusely positive for vimentin and EMA; focally positive for cytokeratin; and negative for CK5/6, CD34, S-100 protein, desmin, and myogenin. INI1 (hSNF5/SMARCB1, a member of the SW1/SNF chromatin remodeling complex located on chromosome 22q11.2) staining clearly showed loss of expression in the tumor cells. Recent studies reported that some ESs also showed INI1 inactivation, as characteristically seen in malignant rhabdoid tumors of infancy. Reported herein is the diagnostic utility of INI-1 on PES and the possible relationship between PES and malignant rhabdoid tumor of the soft tissue, besides a collective review of the reported cases of PES of the vulva and of the current case.

Hemophagocytic lymphohistiocytosis associated with influenza A (H1N1) infection in a patient with chronic lymphocytic leukemia: an autopsy case report and review of the literature - Corrected Proof

Syeling Lai, Brian Y. Merritt, Lei Chen, Xiaodong Zhou, Linda K. Green — 2011-07-04

Abstract: H1N1 influenza A virus can trigger fatal hemophagocytic lymphohistiocytosis in immunocompromised patients and in immunocompetent hosts, usually children. We present a case of a 50-year-old man with low-burden chronic lymphocytic leukemia who had sudden reactivation of his leukemia triggered by influenza A (H1N1) infection with hemophagocytic lymphohistiocytosis during the 2009 H1N1 pandemic. His rapid course was complicated by acute respiratory distress syndrome with diffuse alveolar damage, a 6-fold rise in lymphocyte count, disseminated intravascular coagulation, and, ultimately, cardiac arrest. Major findings at autopsy included: bilateral H1N1 pneumonitis with diffuse alveolar damage, intra-alveolar pulmonary hemorrhage, pulmonary microthromboemboli, pulmonary hemorrhagic infarction, hemophagocytic lymphohistiocytosis in multiple locations, and diffuse chronic lymphocytic leukemia. Hemophagocytic lymphohistiocytosis is a serious and often fatal condition, which may be primary or secondary. It may be associated with high-grade lymphoproliferative malignancies, especially in patients with therapy-related leukocytopenia, but only rarely is it seen in uncomplicated chronic lymphocytic leukemia. Hemophagocytic lymphohistiocytosis may be triggered by a variety of infections (viral, fungal, bacterial and parasitic), but H1N1 influenza A-associated hemophagocytic lymphohistiocytosis is often rapidly fatal, especially in children. This adult patient's clinical presentation with low tumor burden and leukocytosis is thus unique. We review the recently published autopsy findings in fatal influenza A (H1N1) infection and the association with resultant secondary hemophagocytic lymphohistiocytosis.

Pleomorphic hyalinizing angiectatic tumor of renal hilum - Corrected Proof

Muhammad T. Idrees, Theodore Kieffer, Sunil Badve — 2011-07-04

Abstract: Pleomorphic hyalinizing angiectatic tumor (PHAT) is a recently described rare entity. The tumor histogenesis is proposed to be of primitive undifferentiated mesenchyme. The tumor has a predilection for the subcutaneous soft tissue especially of lower extremity, although other locations have been well documented. We report a case of PHAT arising in the hilum of the kidney, clinically mimicking an infiltrating malignant neoplasm of renal pelvis. The tumor was discovered during workup for unrelated gastrointestinal tract symptoms. Because of the location of the lesion, excision of mass and radical nephrectomy were performed. The tumor had strong immunohistochemical expression of vimentin, CD34, CD99, and vascular endothelial growth factor (VEGF). No additional lesions were documented during 3 years of follow-up. This is consistent with the current thinking that PHAT is a benign neoplasm with increased incidence of recurrence. We document the unique retroperitoneal location of this rare tumor and suggest that PHAT should be considered among the list of unusual lesions at this site.

Adenocarcinoma arising in an ectopic mediastinal pancreas - Corrected Proof

Paul St. Romain, Gregory Muehlebach, Ivan Damjanov, Fang Fan — 2011-07-04

Abstract: Pancreatic ectopia in the mediastinum is rare, and there are no reports that it has ever given rise to malignancy. Here we report a case of adenocarcinoma arising in ectopic pancreatic tissue in the mediastinum of a 66-year-old woman. The tumor arose in a partially cystic and partially solid ectopic pancreas containing both exocrine and endocrine components. Thorough clinical examination and clinical follow-up did not reveal other primary sites. The tumor was partially resected but metastasized to the anterior sternum 6 months later and was re-excised. No other similar cases of primary mediastinal pancreatic adenocarcinoma are on record in medical literature.

Metastatic renal mucinous tubular and spindle cell carcinoma. Atypical behavior of a rare, morphologically bland tumor - Corrected Proof

Khin Thway, John du Parcq, James M.G. Larkin, Cyril Fisher, Naomi Livni — 2011-06-20

Abstract: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare, distinctive renal neoplasm characterized by an admixture of cuboidal cells in tubules and sheets of spindle cells, typically with low-grade nuclei and a myxoid or mucinous background. It is characteristically of low malignant potential, and only rare metastatic cases have been reported. We describe a case in which the patient presented with extensive regional and distant metastases, but both primary and metastatic tumor showed the typical histomorphology of bland cuboidal or spindle cells lacking pleomorphism, mitoses, and necrosis. Almost all previous cases of metastatic MTSCCs have shown nuclear atypia or sarcomatoid morphology of the primary tumor; and metastatic renal MTSCC in which the primary neoplasm does not display atypical features is exceptional, serving to highlight that these rare tumors can behave aggressively even with “indolent” histological appearances.

Lymphoepithelial carcinoma of the parotid gland arising in an intraglandular lymph node: report of a rare case mimicking metastasis - Corrected Proof

Sarika Gupta, Kwok Seng Loh, Fredrik Petersson — 2011-06-20

Abstract: We present a case (female patient aged 40 years) with a primary Epstein-Barr virus–associated lymphoepithelial carcinoma of the parotid gland that was confined to an intraparotid lymph node. This appearance of the tumor simulated a metastasis that was excluded by exhaustive radiologic and clinicopathologic investigations.

Sebaceous adenoma arising within an ovarian mature cystic teratoma in Muir-Torre syndrome - Corrected Proof

Jason Smith, Karen Crowe, Julie McGaughran, Thomas Robertson — 2011-06-20

Abstract: This is the first reported case of a sebaceous adenoma arising within an ovarian mature cystic teratoma in a patient with Muir-Torre syndrome. The pathologic findings and a literature review are presented, including the importance and possible benefits of an early diagnosis of Muir-Torre syndrome. It is proposed that the presence of a sebaceous adenoma in an ovarian cystic teratoma may serve as a useful trigger to consider further history and investigations, with the goal of identifying an important genetic cancer predisposition syndrome.

Renal epithelioid angiomyolipoma with epithelial cysts: demonstration of Melan A and HMB45 positivity in the cystic epithelial lining - Corrected Proof

2011-06-15

Abstract: Renal angiomyolipoma (AML) may present as rare variants such as epithelioid and AML with epithelial cysts posing difficulties for the diagnosis to the surgical pathologist. We report a case of a 46-year-old male patient presenting a 5-cm solid tumor in the lower pole of the left kidney, with cystic changes at cut surface. The tumor exhibited 95% of epithelioid cells with atypical nuclei. A small focus of typical AML was observed. The immunoprofile of tumor cells was classical of AML including expression of melanocytic markers such as HMB45 and Melan A. We report the immunohistochemical study of the cystic component in an epithelioid AML. In contrast to the immunoreactivity reported in typical AML, the present case shows obvious expression of melanocytic markers in the cystic epithelial lining. This is strong evidence that these cysts are neoplastic and derived from AML, rather than entrapped native collecting duct epithelium.

Isolated vaginal myeloid sarcoma in a 16-year-old girl - Corrected Proof

2011-06-09

Abstract: Involvement of the female genital tract by myeloid sarcoma as the initial presentation is extremely uncommon, especially in the vagina. The lack of specific histologic features and the unusual location can be a diagnostic challenge to both the surgical pathologist and the clinician. The very few reported cases of myeloid sarcoma occurring in the vagina have been exclusively seen in adults. We report a 16-year-old girl who presented with a vaginal mass of 4 weeks duration. The initial clinical impression was a Bartholin cyst vs an abscess. However, because of persistence of the vaginal mass after a full course of antibiotic treatment, a biopsy was performed. Immunohistochemistry supported the diagnosis of myeloid sarcoma. Peripheral blood and bone marrow studies were normal. The patient received 4 cycles of chemotherapy and remained disease free 5 months from therapy completion. The clinical course, diagnostic workup, and differential diagnosis of our patient are discussed. Reported cases of myeloid sarcoma occurring in the vagina are reviewed and summarized.

Merkel cell carcinosarcoma: Merkel cell carcinoma with embryonal rhabdomyosarcoma-like component - Corrected Proof

Patrick Pak-Lun Lau, S.H. Ting, Y.T. Ip, William Y.W. Tsang, John K.C. Chan — 2011-06-09

Abstract: Merkel cell carcinoma is an uncommon primary neuroendocrine neoplasm of the skin that may exhibit divergent differentiation. However, rhabdomyosarcomatous differentiation has only been rarely described and takes the form of isolated rhabdomyoblasts. We describe a case of cutaneous Merkel cell carcinoma with biphasic morphology imparted by discrete patches of embryonal rhabdomyosarcoma-like spindle cells alternating with islands of neuroendocrine small round cells, justifying a designation of “Merkel cell carcinosarcoma.” The former component showed positive immunostaining for desmin and myogenin; and the later component, pan-cytokeratin, cytokeratin 20, synaptophysin, and chromogranin. The patient was an elderly man who presented with a temporal skin mass, and the biphasic morphology was evident in the recurrence and metastasis that developed 2 months after incomplete excision of the skin lesion.

Large lipoleiomyoma of the uterine body - Corrected Proof

Tadashi Terada — 2011-06-08

Abstract: Large or giant lipoleiomyoma of the uterine corpus is a rare condition. A 70-year-old Japanese woman consulted our hospital because of a pelvic mass and abnormal uterine bleeding. Physical examination showed a mass in the pelvis. Blood laboratory test showed anemia and leukocytosis. Cholesterol, triglyceride, glucose, and hemoglobin A1c were normal. Tumor markers (CEA, CA19-9, CA125, SCC, and CA72-4) were normal. Imaging modalities including ultrasound and computed tomography revealed a characteristic large (8 × 8 × 9 cm) tumor in the posterior aspect of the uterine body. The tumor was characteristic, and the opacity was heterogenous. Radiologists' diagnosis was angiomyolipoma. Simple hysterectomy and bilateral salpingo-oophorectomy were performed. During the operation, it was found that the mass originated from the posterior aspect of the uterine body. Grossly, the resected mass was heterogenous and whitish yellow. It measured 10 × 9 × 9 cm. The tumor originated from the myometrium and assumed features of subserosal leiomyoma. Histologically, the tumor was composed of adipose tissue and smooth muscle cells. The adipose tissue was mature, and there were no atypical cells or lipoblasts. The smooth muscle areas were composed of red spindle smooth muscle cells. No atypia was seen in the smooth muscles. Mitotic figures were not recognized. Vascular proliferation was not seen. The adipose tissue element accounted for 20% in area; and the smooth muscle element, 80%. Immunohistochemically, the adipose tissue element was positive for vimentin and S100 protein, and negative for pancytokeratins (AE1/3, CAM5.2), α-smooth muscle actin, desmin, CD34, HMB45, p53, MDM2, CDK4, and KIT. The smooth muscle element was positive for vimentin, desmin, and α-smooth muscle actin, but negative for pancytokeratins (AE1/3, CAM5.2), S100 protein, CD34, HMB45, p53, MDM2, CDK4, and KIT. The Ki-67 labeling was approximately 0.3% in the smooth muscle element and approximately 0.2% in the adipose tissue element. The pathological diagnosis was large lipoleiomyoma of the uterine body. The patient is now free of the tumor 2 years after the operation.

Thymomas diagnosed during pregnancy: two cases in young women without paraneoplastic or autoimmune disease - Corrected Proof

2011-06-08

Abstract: We report 2 cases of thymomas diagnosed during pregnancy. Neither of these 2 patients had paraneoplastic autoimmune conditions or previous neoplasia. The first patient had a 7.3-cm lymphocyte-predominant thymoma with capsular invasion. The second patient was diagnosed through fine needle aspiration biopsy after computed tomography showed multiple mediastinal masses. Although cases of thymoma during pregnancy have been reported, the exact cause has yet to be elucidated. We review the clinical, radiologic, pathologic, and immunohistochemical findings—including those of podoplanin, estrogen receptor, and progesterone receptor—of 2 previously unreported cases, as well as discuss the relationship of malignancy and pregnancy and review the available literature regarding pregnancy and thymoma.

Solid-pseudopapillary neoplasm of pancreas with long delayed liver metastasis - Corrected Proof

Pablo Gomez, Rebecca Yorke, Alberto G. Ayala, Jae Y. Ro — 2011-06-06

Abstract: Solid-pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm that most commonly affects adolescent girls and young women. Solid-pseudopapillary neoplasm of the pancreas is considered to have malignant potential; 10% to 15% of cases are associated with metastasis, and these usually present at the time of initial diagnoses. Cases with metastases after resection are rare, and all reported cases have occurred less than 5 years after resection. We report a case of SPN in a 36-year-old woman who presented with liver metastasis 15.8 years after complete resection of the primary tumor in the pancreas. To the best of our knowledge, this is the longest time interval reported between resection of primary tumor and subsequent detection of metastatic disease. Solid-pseudopapillary neoplasm of the pancreas can present with metastases many years after resection of the primary tumor. Long-term follow-up is warranted, given the possibility of late metastasis.