Significant Nuclear Pleomorphism Research Articles

GLI1-Altered Mesenchymal Tumors With ACTB or PTCH1 Fusion: A Molecular and Clinicopathologic Analysis

Mesenchymal tumors with GLI1 fusions or amplifications have recently emerged as a distinctive group of neoplasms. The terms GLI1-altered mesenchymal tumor or GLI1-altered soft tissue tumor serve as a nosological category, although the exact boundaries/criteria require further elucidation. We examined 16 tumors affecting predominantly adults (median age: 40 years), without sex predilection. Several patients had tumors of longstanding duration (>10 years). The most common primary site was soft tissue (n = 9); other sites included epidural tissue (n = 1), vertebra (n = 1), tongue (n = 1), hard palate (n = 1), and liver (n = 1). Histologically, the tumors demonstrated multinodular growth of cytologically uniform, ovoid-to-epithelioid, occasionally short spindled cells with delicate intratumoral vasculature and frequent myxoid stroma. Mitotic activity ranged from 0 to 8 mitoses/2 mm2 (mean 2). Lymphovascular invasion/protrusion of tumor cells into endothelial-lined vascular spaces was present or suspected in 6 cases. Necrosis, significant nuclear pleomorphism, or well-developed, fascicular spindle-cell growth were absent. Half demonstrated features of the newly proposed subset, “distinctive nested glomoid neoplasm.” Tumors were consistently positive for CD56 (n = 5/5). A subset was stained with S100 protein (n = 7/13), SMA (n = 6/13), keratin (n = 2/9), EMA (n = 3/7), and CD99 (n = 2/6). Tumors harbored ACTB::GLI1 (n = 15) or PTCH1::GLI1 (n = 1) fusions. The assays used did not capture cases defined by GLI1 amplification. We also identified recurrent cytogenetic gains (1q, 5, 7, 8, 12, 12q13.2-ter, 21, and X). For patients with available clinical follow-up (n = 8), half were disease free. Half demonstrated distant metastases (lungs, bone, or soft tissue). Of cases without follow-up (n = 8), 2 were known recurrences, and 1 was presumed metastasis. Our results imply a more aggressive biological potential than currently reported. Given the possibility for metastasis and disease progression, even in cytologically bland, nested tumors, close clinical surveillance, akin to that for sarcoma management, may be indicated. The term GLI1-altered mesenchymal tumor with malignant potential is proposed.

ODP497 Multifocal Papillary Thyroid Carcinoma with Anaplastic Dedifferentiation

Abstract A 71-year old male with a two-year history of progressively enlarging right thyroid mass presented with hemoptysis. Chest CT scan showed multiple pulmonary nodules and enlarged right thyroid mass with intrathoracic extension. A fine needle biopsy of the right thyroid mass showed atypia of undetermined significance. Patient underwent total thyroidectomy and complete resection of the intrathoracic component. Histopathology reported multifocal Papillary thyroid carcinoma, right lobe, encapsulated follicular variant (9cm) with extensive and vascular invasion. There was also invasion of the left thyroid lobe, follicular variant, infiltrative (0.6 cm) and conventional (0.6 cm). Extrathyroidal extension to skeletal muscle and lymphovascular invasion was present. The tumor showed areas with more solid growth patterns and some ball-like clustering. Consequently, immunostaining was done which showed the following results: positive for cytokeratin, thyroglobulin and TTF-1 consistent with papillary morphology. The more solid areas with significant nuclear pleomorphism, necrosis and increased mitotic activity (atypical forms) support the focal progression to an anaplastic carcinoma. The final histologic reading showed multifocal papillary thyroid carcinoma with focal (20%) progression to undifferentiated (anaplastic) thyroid carcinoma. Two weeks postoperatively, he developed a 4cm×2cm manubrium mass. There were also several metastases on the brain, pancreas, liver and bones seen on FDG PET scan. One month postoperatively, TSH was 15 uIU/mL Thyroglobulin >500 uIU/mL, anti-thyroglobulin <0.20 ng/dl. Due to the widespread metastases even involving the brain, the multidisciplinary team decided to start treatment with Lenvatinib and check for BRAF V600E gene mutation for a more definitive treatment. He was started on Levothyroxine. He also underwent 27 cycles of radiation therapy to the manubrium mass and was given Denosumab 120mg subcutaneously to stabilize the bone and provide pain relief. BRAF gene mutation analysis result came back negative in two weeks. Close monitoring of his sensorium was done. However, he deteriorated clinically and he succumbed to sudden cardiac death two months after. Presentation: No date and time listed

S3613 Gastric Spindle Cell Leiomyosarcoma Is Associated With Chronic Helicobacter pylori Infection

Introduction: Chronic Helicobacter pylori (HP) infection has been shown to be strongly associated with development of gastric malignancies, mostly gastric adenocarcinomas and lymphomas. We present a case of primary gastric leiomyosarcoma in a patient with persistent epigastric pain and HP infection. Case Description/Methods: A 59-year-old female presented to clinic with persistent, postprandial epigastric pain. Cardiopulmonary workup was negative. She had a history of esophageal leiomyoma resected endoscopically with negative margins 10 years ago. She was treated in the past for HP infection but never had repeat testing to confirm eradication. Abdominal computed tomography showed focal hepatic infiltration. She was advised to have a repeat upper endoscopy for surveillance but was lost to follow-up due to psychiatric comorbidities. She presented 6 years later with epigastric pain. Repeat CT abdomen showed a new 2.8 cm hypoattenuating lesion in the lesser curvature of the stomach. Patient did not follow up due to psychosocial issues. Two years later, she returned to clinic for epigastric pain and underwent repeat upper endoscopy and endoscopic ultrasound (EUS) with fine needle aspiration (FNA). EGD showed sub-gastric nodule attached gastric wall, about 30 mm in maximal dimension and gastric biopsy confirmed active HP infection. The EUS showed a 31.7x23.5 mm hypoechoic homogeneous gastric mass along the lesser gastric curvature. Cytology showed cellular spindle cell neoplasia with myogenic differentiation concerning for possible leiomyoma or leiomyosarcoma. Abdominal magnetic resonance imaging and chest computed tomography revealed no evidence of abdominal or thoracic metastasis. Subsequently, partial underwent sleeve gastrectomy. Pathology revealed Grade 1 myxoid leiomyosarcoma with negative margins. (Figure) Discussion: Prior studies demonstrated associations between HP infection and gastric malignancies - typically gastric adenocarcinoma or lymphomas. Few studies investigated the relationship between HP infection and gastric leiomyosarcomas.4,5 Importantly, this patient never had clearance of HP infection and may have allowed a leiomyosarcoma to develop. It is imperative that clinicians confirm eradication of HP infection given risk of leiomyosarcoma development in addition to other malignancies HP infections are known to cause.Figure 1.: Endoscopic and histologic examination of gastric leiomyosarcoma. (A) Endoscopic ultrasound visualization demonstrating tumor within lesser curvature of stomach. (B) Upper endoscopy revealing tumor approximately 4 cm from gastroesophageal junction. (C) Hematoxylin and eosin (H&E) stain of gastric tumor biopsy demonstrating spindle cell proliferation in a myxoid background with significant nuclear atypia and pleomorphism consistent with myxoid leiomyosarcoma. Magnification x400. (D) Immunohistochemical staining of gastric lesion biopsy demonstrating strong immunoreactivity to desmin. Not shown are positive stains for smooth muscle actin (SMA) as well as negative stains for Cytokeratin AE1/AE3, Myogenin, MyoD1, DOG-1, CD117, S100, SOX10, CD34, ALK-1 and ER. Positive and negative controls stained appropriately but are not included.

Cytomorphologic findings of thyroid carcinoma showing thymus-like (CASTLE) differentiation: A case report

Abstract Introduction/Objective Thyroid carcinoma showing thymus-like differentiation also known as intrathyroidal thymic carcinoma is a rare thyroid neoplasm arising from either an ectopic intrathyroidal thymic tissue or from remnants of thymobranchial pouches. On fine needle aspiration (FNA) its diagnosis can be challenging due to overlapping morphologic features with other aggressive thyroid carcinomas. Methods/Case Report A 31-year-old female consulted for 6-month history of neck swelling and tenderness. Thyroid ultrasound demonstrated a 2.6 x 2.5 x 2.1 cm nodule in the right lobe with punctate calcifications. FNA showed cellular smears composed of loosely cohesive and single basaloid neoplastic cells exhibiting significant cellular and nuclear pleomorphism. Focal squamous differentiation with keratinization was noted on the cell block sections. Immunocytochemical stains showed that the tumor was positive for cytokeratin AE1/AE3, p40, p63, CD117 and CD5 consistent with intrathyroidal thymic carcinoma. The Ki67 proliferative index was approximately 40%. A right thyroidectomy with central neck dissection confirmed the diagnosis and showed a 3.0 cm tumor with invasion into skeletal muscle, lymphovascular invasion and positive lymph nodes. The patient completed adjuvant radiotherapy and remain in remission at 3-months follow-up. Results (if a Case Study enter NA) NA Conclusion Intrathyroidal thymic carcinoma is a rare thyroid neoplasm that frequently shows squamous differentiation and therefore overlaps with papillary thyroid carcinoma with squamous morulae, squamous cell carcinoma and anaplastic carcinoma. The coexpression of squamous markers together with CD5 and CD117 allows the recognition of CASTLE on FNA samples.

Noninvasive low-grade papillary urothelial carcinoma with degenerative nuclear atypia: a grading pitfall

Noninvasive low-grade papillary urothelial carcinoma is a papillary neoplasm with orderly appearance and mild nuclear pleomorphism. Some cases show significant nuclear pleomorphism with degenerative atypia leading to grading difficulties. A retrospective review of the pathology files identified 16 cases diagnosed as noninvasive low-grade papillary urothelial carcinoma with degenerative atypia. Fifteen cases were consults. The average age was 46 years (range 19-78). The average size was 1.7cm (range: 0.3-3.5). The submitting diagnoses in consults were noninvasive high-grade papillary urothelial carcinoma (n=6), condyloma (n=1), atypical papillary lesion (n=1), prominent umbrella cells (n=1), and not given (n=6). Ki-67 proliferation rate was <5% in 10 of 10cases (100%), and the cells with large atypical nuclei were negative. Microscopically, there were scattered cells with nuclei larger than 5 times the size of stromal lymphocytes but displayed smudgy chromatin and occasional multinucleation and intranuclear vacuoles. Next-generation sequencing identified the following mutations: HRAS (n=4), FGFR3 (n=3), KRAS (n=3), BRAF (n=1), PDGFRA (n=1), and PIK3CA (n=1). Other deleterious mutations were identified, but none in genes characteristic of high-grade tumors. Follow-up was available in 6 patients (median 32 months). One patient recurred with a noninvasive low-grade papillary urothelial carcinoma 20 months after the index case. All the remaining patients had no evidence of disease at the last follow-up. No patient died or had disease progression. The combination of preservation of polarity, low mitotic activity, Ki-67<5% with the larger atypical nuclei negative for Ki-67, along with nuclear atypia that is degenerative are features used to classify these tumors as low grade.

CYTO HISTOLOGIC CORRELATION OF A LOW GRADE FIBROMYXOID SARCOMAAT AN UNUSUAL LOCATION – A CASE REPORT

BACKGROUND Low grade fibromyxoid sarcoma (LGFMS) is a rare tumour of the deep soft tissues seen in young adults. The histologic features of LGFMS are well established, however the cytologic findings are scantily defined and the distinction from other benign and malignant myxoid soft tissue tumours is difficult. CASE DETAILS A 29 year old male presented with a superficial swelling in the left areolar region for two months. USG revealed a well-defined 2 by 2 cm hyperechoic lesion extending upto the subcutaneous fat. FNA yielded mucoid material and smears showed spindle cells having round to elongated nuclei with mild anisokaryosis, bland chromatin and wispy cytoplasm in a myxoid background. No significant nuclear pleomorphism or mitoses were noted. A diagnosis of myxoid mesenchymal lesion was made. The excised tumour was well circumscribed with grey white cut surface showing myxoid areas. Microscopically, the tumour displayed moderate cellularity with storiform, intersecting and parallel bundles of spindle cells showing mild nuclear pleomorphism. The myxoid areas showed cells in a haphazard fashion floating in abundant mucoid matrix associated with a capillary network. The mitotic index was low. IHC showed tumor cells positive for vimentin and negative for S-100 &amp; SMA. CONCLUSION LGFMS is a rare low-grade malignancy with a high local recurrence rate and late metastasis. The diagnosis of LGFMS can be difficult to render from fine needle aspiration cytology (FNAC) alone because of morphological overlap with other spindle cell and myxoid lesions. Cytohistological correlation and IHC is helpful in arriving at a correct diagnosis.

Navigating the Differential Diagnosis for Oncocytic Salivary Gland Lesions (Cytology and Histology)

Abstract Oncocytic lesions of the parotid gland include nonneoplastic entities and benign and malignant neoplasms. The most common benign neoplasm is Warthin tumor, which can be correctly diagnosed using fine-needle aspiration (FNA) or core biopsy in most cases. However, accurate FNA and/or biopsy preoperative diagnosis of many entities in this category is limited by sampling and overlap in morphological features among the different entities. We report the case of a 77-year-old man who presented with a right parotid mass identified on magnetic resonance imaging and computed tomography scan that was cystic with necrosis and with possible papillary growth in the cyst. The FNA smears were scantly cellular, with a few representative groups with significant nuclear crowding and overlapping in a bloody background. The cells had oncocytic cytoplasm, an increased nuclear-to-cytoplasmic ratio, and round-to-oval nuclei with prominent nucleoli. Necrosis, mitoses, and significant nuclear pleomorphism were not identified. The findings were interpreted as consistent with an oncocytoid/oncocytic salivary gland neoplasm. The cell block was acellular, so the neoplasm could not be further characterized by ancillary studies. The patient underwent a right superficial parotidectomy. The histopathological diagnosis was oncocytic carcinoma primarily based on the identification of perineural invasion. Oncocytic carcinoma is a rare, high-grade malignancy of salivary glands. This case will be used to discuss the differential diagnosis of oncocytoid/oncocytic salivary gland lesions on both cytopathology and histopathology and provide a pragmatic approach to the diagnostic evaluation. Indications for available ancillary testing will also be reviewed.

Dedifferentiated Liposarcoma With Meningothelial-Like Whorls: Five Additional Cases and Review of the Literature.

Background. Diagnosis of dedifferentiated liposarcoma (DDL) can sometimes be challenging due to a wide variety of histological features. "Meningothelial-like" whorl is an uncommon histological feature of DDL, which is also observed in neural tumors and follicular dendritic cell sarcoma. This feature is frequently associated with metaplastic bone formation. We conducted this study to describe the clinicopathological features of DDL with meningothelial-like whorls that would aid in establishing accurate diagnosis. Material and Methods. Microscopic glass slides of 5 cases of DDL with meningothelial-like whorls, diagnosed between January 2010 and December 2019, were reviewed. Results. Paratesticular region was the most common site. Whorls occupied 10% to 75% of tumor area and ranged in size from <0.1 cm to >2 cm. In 1 case, these whorls coalesced to form large areas of dedifferentiation. The cells forming whorls were spindle to epithelioid shaped and lacked significant nuclear pleomorphism and increased mitoses. Metaplastic bone formation was observed in 4 cases and cartilage formation in 3 cases. p16 and α-smooth muscle actin (α-SMA) immunohistochemical stains were positive in 2 cases, when performed. MDM2 gene amplification was observed in all cases by fluorescence in situ hybridization technique. These tumors showed aggressive behavior, similar to that of DDL without meningothelial-like whorls. Two patients died, 1 developed recurrence, 1 presented as recurrent tumor, and 1 developed metastasis. Conclusion. Meningothelial-like whorls in DDL most likely represent an early stage of dedifferentiation. Presence of well-differentiated liposarcoma areas, metaplastic bone formation, positive expressions for p16 and α-SMA immunohistochemical stains, and MDM2 gene amplification are useful diagnostic clues. These tumors have the potential to behave aggressively.

Clinicopathological study of BCOR rearrangement in high grade endometrial stromal sarcoma

Objective: To investigate clinicopathological, cytogenetic features and differential diagnoses of high grade endometrial stromal sarcoma (HGESS) with BCOR gene rearrangement. Methods: Five cases of HGESS with BCOR rearrangement were collected from consultant files (2016-2018) at Fudan University Shanghai Cancer Center. Interphase FISH was performed using a dual color break-apart probe. The clinical data, histologic features and immunohistochemical findings were reviewed. Results: All 5 cases occurred in adult women with a median age of 48 (range, 45-55) years. Abdominal pain and abnormal vaginal bleeding were the most common symptoms. Microscopically, the tumors showed mainly tongue-like and/or intersecting myometrial invasion. Stromal myxoid matrix and/or collagen plaques were prominent in all the cases. Most tumors consisted of uniform, haphazard fascicles of short spindle cells with mild to moderate nuclear atypia. Mitotic figures and necrosis were easily identified. Significant nuclear pleomorphism was not seen. Most tumors were rich in thick-walled small vessels. Prominent perivascular tumor cell whorling seen in conventional low-grade endometrial stromal sarcoma was not seen. All tumors expressed CD10 with only focal or absent desmin, SMA and/or h-caldesmon staining. ER or PR expression was seen in 4 tumors and 1 tumor showed both marker expression. Diffuse cyclin D1 was present in 2 tumors. BCOR immunoreactivity was present with strong staining in 3 cases and moderate staining in 1 case respectively. Ki-67 index ranged from 10% to 30%. Fluorescence in situ hybridization confirmed chromosomal aberration of BCOR gene in all tumors, that were previously diagnosed as myxoid leiomyosarcoma (2 cases), spindle cell uterine sarcoma (2 cases) and low-grade endometrial stromal sarcoma (1 case). Limited follow-up information revealed that 3/5 patients developed tumor recurrence, metastasis or death within one year. Conclusion: BCOR rearranged HGESS has distinct morphological features and aggressive clinical behavior. In the presence of significant overlapping morphologic features between BCOR rearranged HGESS and other myxoid uterine mesenchymal tumors, especially myxoid leiomyosarcoma, molecular analysis is essential for accurate diagnoses.

Coexisting pancreatic serous cystadenoma and pancreatic ductal adenocarcinoma: A cytological-pathologic correlation with literature review

Pancreatic serous cystadenoma (SCA) is a benign neoplastic lesion with a distinctive gross and microscopic appearance consisting of numerous thin-walled cysts lined by uniform epithelial cells with clear cytoplasm and small nuclei. The vast majority of serous cystadenomas are benign. Pancreatic SCA has rarely been reported in association with other pancreatic lesions. We present a challenging case in which a cystic and solid pancreatic mass was identified on imaging studies. FNA was performed and showed clusters of atypical cells with significant nuclear pleomorphism (>4:1), disorganized, overlapping nuclei, and prominent nucleoli. The FNA diagnosis was positive for malignancy, consistent with adenocarcinoma. The patient underwent neoadjuvant therapy and pancreaticoduodenectomy. Final pathology showed a serous cystadenoma associated with small foci of high-grade PanIN. The lack of invasive adenocarcinoma in the resection specimen was most likely due to complete response of the tumor to neoadjuvant chemoradiation therapy, but it is also possible that only high-grade PanIN was present initially. To our knowledge, this is the first reported case of SCA and high grade PanIN/PDAC that was assessed by FNA. We discuss the cytologic differential diagnosis and how to avoid potential pitfalls highlighted by this case.

Hepatoid Carcinoma of the Ovary: Clinical, Histopathologic, and Immunophenotypic Features.

Hepatoid carcinoma of the ovary (HCO) is a rare malignant tumor of uncertain histogenesis that was first described by Ishikura and Scully in the late 1980s. Unlike hepatoid yolk sac tumor (HYST), one of its main differential diagnoses, HCO usually presents in perimenopausal and postmenopausal women without gonadal dysgenesis. Most cases show advanced local disease at initial presentation, with diffuse intraperitoneal dissemination. Despite aggressive treatment, including surgery and adjuvant chemotherapy, 61.5% of patients either die of the disease (11 of 26; 42.3%) or are alive with recurrent or residual disease (5 of 26; 19.2%) after a median follow-up of 11.5 months (range, 1-60 months). Most HCOs are solid, with high-grade histology, significant nuclear pleomorphism, scattered giant cells, and a high mitotic index. Their immunophenotype is defined by the expression of broad-spectrum cytokeratins, α-fetoprotein, and hepatocellular antigens with absence of sex cord and germ cell markers. Although immunohistochemistry can be very helpful to distinguish between sex cord-stromal tumors and HCO, differentiation of the latter from HYST, metastatic hepatocellular carcinoma, and metastatic gastrointestinal tumors with hepatoid phenotype requires integration of clinical, radiologic, and pathologic information.

Giant Cell Tumor of Soft Tissues: A Case Report and Review of Literature

Background: Primary giant cell tumor (GCT) of soft tissue (GCTST) is an extremely rare slow-growing entity bearing a high similarity to conventional bone TCG (GCTB). The term, malignant tumor of giant cells of soft tissues have been reserved for histologically high-grade lesions. Although the gold standard remains surgical carcinological resection, bisphosphonates are beginning to prove their benefit in the treatment of GCTST. Results and Discussion: A 37-year-old man came to the outpatient department of medical oncology with a painful swelling arising from his right elbow. Magnetic resonance imaging (MRI) of the right elbow was done and revealed a 19 cm × 7 cm, T1 and T2 hypointense lesion with significant postcontrast enhancement of calcified tissue nodules, distance extension report was negative. An echo-guided biopsy of the right elbow was performed. The anatomopathological examination showed a poorly delimited encapsulated tumor proliferation composed of sheets of histiocytic cells admixed with multinucleated giant cells dispersed uniformly among this tumor. Cells were embedded in a richly vascularized tissue. No significant nuclear pleomorphism or mitotic activity was appreciated. There were focal areas of osseous metaplasia. On the basis of these date, the diagnosis of giant cell tumor of low malignant potential was retained. Due to its intra-articular extension, the mass was judged unresecable. The case was discussed in a multidisciplinary consultation meeting indicating medical treatment with zoledronic acid given the unavailability of denosumab. After 8 monthly injections of zoledronic acid, a control imaging of the right elbow and forearm concluded to tumor stability. Conclusion: GCTST is a slow-growing tumor known as soft tissue tumor. Numerous studies show the role of bisphosphonates when complete surgical excision cannot be performed. Further studies are needed to establish a standardized treatment protocol particularly in the context of inoperable large primary GCTST.

Expression of anaplastic lymphoma kinase and its clinical significance in non-small cell lung cancer

To investigate the frequency of anaplastic lymphoma kinase (ALK) expression in non-small cell lung cancer (NSCLC) patients and its correlation with the clinicopathologic features. ALK immunohistochemistry and ALK fluorescent in situ hybridization (FISH) were performed on formalin-fixed, paraffin-embedded tissue in 100 cases of NSCLCs between 2011 and 2013. Relevant clinicopathologic data were collected and correlated with ALK expression. All patients with immunohistochemical score of 3 (n = 12) were FISH-positive and all patients with score of 0 (n = 78) were FISH-negative. Among patients with immunohistochemical scores of 1 and 2, 2/3 and 6/7 were FISH-positive, respectively. The sensitivity and specificity of ALK immunohistochemistry with intensity score of 1 or more were 100% and 98%, respectively. Invasive mucinous adenocarcinoma, solid or acinar growth pattern, presence of mucous cells (signet-ring cells or goblet cells), extracellular mucus and lack of significant nuclear pleomorphism characterized ALK-rearranged cancer. ALK-rearranged cancers possess specific histological features. Immunohistochemistry can be used as a routine test for screening ALK-positive cases in advanced NSCLC, and FISH testing should be used to confirm ALK translocation for patients with tumors showing staining for ALK by immunohistochemistry. All of these can help physicians identify patients who may benefit from targeted therapy.

Clinicopathological analysis of intraductal proliferative lesions of prostate: intraductal carcinoma of prostate, high-grade prostatic intraepithelial neoplasia, and atypical cribriform lesion.

Intraductal carcinoma of the prostate (IDC-P) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two distinct intraductal lesions; the former is usually associated with invasive carcinoma and has an aggressive course while the latter is considered a precancerous lesion. In addition, there are morphologically lesions not well characterized that fall between IDC-P and HGPIN, consequently termed "atypical cribriform lesions (ACLs)." Using whole mount radical prostatectomy specimens, we evaluated the relationship between these intraductal proliferative lesions and clinicopathological parameters. In this study, ACLs were characterized as a loose cribriform intraductal proliferation with greater architectural complexity when compared to HGPIN, but lacking significant nuclear pleomorphism and/or comedonecrosis. Of 901 radical prostatectomies (2006-2012), IDC-P, ACL, and HGPIN were recorded in 155, 22, 436 cases, respectively. Patients with IDC-P showed more aggressive pathologic features when compared to HGPIN. Invasive cancers in patients with ACL had higher Gleason score (P=.00016), larger tumor volume (P=.025), and more advanced pT stage (P=.023) than those with HGPIN. Cases with ACL showed a higher risk of biochemical recurrence than those with HGPIN and a lower risk than those with IDC-P based on log-rank tests (P=.0045 and P=.0069, respectively). In multivariate analysis, the presence of HGPIN was identified as an independent predictor for infrequent biochemical recurrence (P=.0058). We confirmed IDC-P as a marker of adverse pathologic features and clinical aggressiveness. Our results suggest that ACL should be distinguished from HGPIN and these lesions mandate active clinical surveillance.

Architectural Versus Nuclear Atypia-defined FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma (EEC)

International Federation of Gynecology and Obstetrics (FIGO) Grade 2 endometrial endometrioid adenocarcinoma carries a 88% 5-yr survival rate. They are defined by >5% but <50% solid epithelial component. A small subset may display <5% solid growth, but marked nuclear atypia and are designated Grade 2. We compared tumor characteristics, staging, and clinical outcome of patients with architectural versus atypia-defined Grade 2 endometrial endometrioid adenocarcinoma. A total of 154 Grade 2 endometrial endometrioid adenocarcinoma cases were reviewed to confirm grade; percent solid growth, and presence of atypia. Only marked atypia (significant nuclear pleomorphism identifiable at 10× or enlarged nuclei, 1.5 to 2× normal, with irregular nuclear contours, dispersed chromatin, and prominent nucleoli) increased the FIGO Grade 1 level. Depth of invasion, tumor stage, lymph node status, and clinical outcomes were then compared. A total of 154 cases were evaluated. Twenty-three were eliminated (6 Grade 3, 17 Grade 1). Of the 131 FIGO II cases, 19 (15%) were based on the presence of severe atypia and 112 (85%) met the architecturally defined criteria. Atypia-defined versus architecturally defined Grade 2 endometrial endometrioid adenocarcinoma's show no significant difference in stage and prognosis. An increase in grade based on presence of nuclear atypia stratifies patients at increased risk as 89% of these patients have myoinvasion at the time of hysterectomy which is in distinct contrast to our previous study (International Journal of Gynecologic Pathology. 2012 July; 31(4): 337-43), where 70% of Grade I cases were noninvasive. No significant correlation between percentage of solid component and risk of recurrence was identified in this study.

Fine needle aspiration cytology findings of mucinous carcinoma of breast: a study of eight cases with histological correlation

Background: Pure mucinous carcinoma is a rare histologic type of mammary neoplasm and may exist as mixed mucinous-ductal carcinoma. This study aims to describe fine needle aspiration cytology features of mucinous carcinoma of breast diagnosed in Tribhuvan University Teaching Hospital, Nepal over the period of 2 years and to correlate with histological findings.Materials and Methods: There were a total of 8 cases of mucinous carcinoma of breast, diagnosed on fine needle aspiration cytology in TUTH during the period from April 2010 to March 2012. The patient’s age, laterality of involvement, fine needle aspiration cytology features, gross and histological findings, type of surgery performed and tumor size were evaluated. Fine needle aspiration cytology smears were evaluated for cellularity, amount of mucin, chicken-wire vasculature and nuclear atypia.Results: Fine needle aspiration cytology provided a pre-operative diagnosis of mucinous carcinoma in 5 cases and mixed mucinous carcinoma-invasive ductal carcinoma in 3 cases. Histological examination showed pure mucinous carcinoma in 3 cases, mixed mucinous carcinoma-invasive ductal carcinoma in 4 cases and mixed cribriform carcinoma and ductal carcinoma in 1 case.Conclusion: Mucinous carcinoma may appear clinically and radiologically benign and fine needle aspiration cytology plays important role in the correct pre-operative diagnosis. Significant nuclear pleomorphism and necrosis, in addition to extracellular mucin suggests mixed mucinous carcinomainvasive ductal carcinoma.Journal of Pathology of Nepal (2012) Vol. 2, 285-288DOI: http://dx.doi.org/10.3126/jpn.v2i4.6879

Solid Pattern Yolk Sac Tumor

Yolk sac tumors may exhibit numerous patterns. One that has received little attention overall, yet is not uncommon, is a solid pattern, which is especially prone to misinterpretation, usually as seminoma, in biopsy specimens from metastatic or mediastinal sites. This distinction is of critical importance as the 2 tumors are treated differently. To determine features useful in the diagnosis of solid yolk sac tumor we reviewed 52 germ cell tumors (28 testicular primaries, 21 metastases from the testis, and 3 mediastinal primaries) that had a yolk sac tumor component with foci of solid growth, defined as a sheet-like arrangement of tumor cells occupying >2 mm and with no or only rare microcysts. Solid yolk sac tumor was almost always associated with other patterns, most commonly microcystic/reticular (75%), glandular (35%), and myxoid (25%). The solid foci consisted of sheets of cells with usually abundant cytoplasm that was mostly (85%) pale to clear and frequently had intercellular basement membrane deposits (75%), rare microcysts (67%), significant nuclear pleomorphism (65%), and hyaline globules (65%). In 2 cases (4%), the cells were small with scant cytoplasm (blastema-like variant). A myxoid background (39%), lymphocytic infiltrate (17%), and an appliqué pattern (8%) were sometimes observed. On immunostaining, AE1/AE3 cytokeratin and glypican 3 provided the most intense and diffuse reactivity for solid yolk sac tumor, whereas α-fetoprotein was negative in 38%. CD117 stained 59%, whereas only rare cells in 1 case (3%) were weakly reactive for podoplanin; OCT3/4 was uniformly negative. We conclude that solid yolk sac tumor can generally be recognized by careful morphologic evaluation, especially its association with other yolk sac tumor patterns, the presence of intercellular band-like deposits of basement membrane, occasional microcysts, nuclear pleomorphism, intracellular hyaline globules, and usual absence of lymphocytes. In difficult cases a concise immunohistochemical panel consisting of AE1/AE3, glypican 3, and OCT3/4 distinguishes solid yolk sac tumor from other neoplasms. α-fetoprotein stains are commonly negative or weak and focal in solid yolk sac tumor and cannot be solely relied on for diagnosis. Common CD117 positivity in solid pattern yolk sac tumors makes it an unreliable discriminator between yolk sac tumor and seminoma.

Case report: parotid basal cell adenoma, membranous type

A52-year-old female withbackgroundofnon-Hodgkin's lymphoma and polymyositis presented with a 4 year history of slow growing, left parotid mass. There were no other associated symptoms. Fine needle aspirate of the mass was performed and the diagnosis of an atypical primary salivary gland neoplasm was made. Subsequent left parotidectomy was performed and the diagnosis of parotid basal cell adenoma, membranous type was made. Basal cell adenoma is a benign epithelial neoplasm of the salivary gland which is characterised by uniform proliferation of basaloid cells. Basal cell adenoma often occurs in the parotid gland followed by the submandibular gland and the upper lip region. Basal cell adenoma accounts for 1–3% of all benign parotid tumours, and the peak incidence is in the 6th to 7th decades of life. There are various subtypes based on morphological features which include solid, trabecular, tubular, and membranous types. The membranous subtype has been associated with the dermal cyclindromas which have similar incidence of chromosomal alteration at 16q12– 13. The membranous subtype is characterised by tumour cells arranged in a jig-saw like pattern with prominent PAS+ eosino-philic, basement-membrane type material. The main differential diagnosis is basal cell adenocarcinoma, and it can be difficult to distinguish between the two. Basal cell adeno-carcinoma is characterised by increased number of mitotic figures, increased nuclear pleomorphism, infiltrative growth, and peri-neural and intravascular invasion. In our case, the proliferative index Ki-67 is low, and there is no significant nuclear pleomor-phism, infiltrative growth pattern, or perineural invasion. However, the lesion extends to the diathermied margin, which is associated with a higher rate of recurrence of approximately 25%.

Pathology Quiz Case 2

A 46-YEAR-OLD MAN PRESENTED WITH A several-month history of dysphagia. He was otherwise healthy, denied tobacco or alcohol use, and reported a history of tonsillectomy. His voice was clear. Flexible laryngoscopy demonstrated a polypoid mass that filled the right piriform sinus and spilled into the laryngeal introitus (Figure 1). The vocal folds were mobile. A contrast computed tomogram of the neck showed a cystic-solid lesion in the region of the right piriform sinus, with an associated mass effect. The patient elected to undergo transoral laser excision of the hypopharyngeal mass. The resection was performed with suspension laryngoscopy and a handheld carbon dioxide laser (OmniGuide, Cambridge, Massachusetts). Multiple masses were resected, and it was confirmed that they emanated from the piriform sinus. Gross examination revealed multiple tan-gray, irregularly shaped tissue fragments measuring 4.1 3 1.2 cm, with 1 area showing smooth, gray mucosa. Sectioning showed tan-gray firm tissue. Histologic analysis demonstratedanodular areaofblandspindlecellproliferationwithout a capsule in the submucosa, with interspersed mature fatty tissue in the periphery (Figure 2). The spindle cells were arranged in a nondescript pattern with meshworks of small vessels (Figure3). No specific architecture, such as a herring bone or hemangiopericytic pattern, was noted. No significant nuclear pleomorphism, mitosis, necrosis, or hemorrhage was present. There was no evidence of dysplasia or malignancy. Immunohistochemical stains were strongly positive for vimentin and CD34 (Figure 4) and negative for smooth muscle antigen, S-100 protein, keratin, and neurofilament in the spindle cells. What is your diagnosis?

Comprehensive Histologic Analysis of ALK-Rearranged Lung Carcinomas

A subset (1% to 5%) of non-small-cell lung carcinomas harbors the EML4-ALK fusion gene. Data from previous studies on the histomorphology of ALK-rearranged lung cancer are inconsistent, and the specific histologic parameters that characterize this subset and how accurately such parameters predict underlying ALK abnormality remain uncertain. To answer these questions, we performed a comprehensive histologic analysis of 54 surgically resected, extensively sampled ALK-rearranged lung carcinomas and compared them with 100 consecutive resections of ALK-wild-type lung cancers. All 54 cases showed at least a focal adenocarcinoma component, and 3 and 2 cases had additional squamous and sarcomatoid differentiation, respectively. Solid or acinar growth pattern, cribriform structure, presence of mucous cells (signet-ring cells or goblet cells), abundant extracellular mucus, lack of lepidic growth, and lack of significant nuclear pleomorphism were more common in ALK-positive cancers. Two recognizable constellations of findings, a solid signet-ring cell pattern and a mucinous cribriform pattern, were present at least focally in the majority (78%) of ALK-positive tumors, but were rare (1%) in ALK-negative tumors. Multivariate analysis showed that a combination of these 2 patterns was the most powerful histologic indicator of ALK rearrangement. Characteristic histologies were present both in primary sites and in metastases. Thus, histologic findings may help to identify cases for ALK testing. However, none of the histologic parameters were completely sensitive or specific to ALK rearrangement, and histomorphology should not replace confirmatory molecular or immunohistochemical studies. ALK-positive cancers commonly showed coexpression of thyroid transcription factor-1 and p63, and its significance is currently unclear.