Elizabeth E. Frauenhoffer

Variance in the Interpretation of Cervical Biopsy Specimens Obtained for Atypical Squamous Cells of Undetermined Significance

We sought to determine whether the variability in dysplasia rates in cases of atypical squamous cells of undetermined significance (ASCUS) reflects variability in interpretation of cervical biopsy specimens. In phase 1, 124 biopsy specimens obtained because of a cytologic diagnosis of ASCUS were reviewed independently by 5 experienced pathologists. Diagnostic choices were normal, squamous metaplasia, reactive, indeterminate, low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL). The rate of dysplasia ranged from 23% to 51%. All pathologists agreed in 28% of cases. In 52% of cases, the diagnoses ranged from benign to dysplasia. The overall interobserver agreement was poor. In phase 2, 60 cervical biopsy specimens (21 obtained for ASCUS, 22 for LSIL, and 17 for HSIL) were evaluated using the same diagnostic choices. Agreement was better in biopsies performed for HSIL and LSIL compared to those for ASCUS. Intraobserver reproducibility in the interpretation of biopsies performed for ASCUS ranged from poor to excellent. We conclude that variability in the interpretation of biopsy specimens plays an important role in the differences in rates of dysplasia reported for the follow-up of ASCUS.

Thyroid Lymphoma: A Single Institution's Experience

BACKGROUND: Primary lymphoma of the thyroid gland is uncommon. METHODS: The tumor registry at the Penn State Milton S. Hershey Medical Center was searched for all patients carrying a diagnosis of thyroid lymphoma. All available records for these patients were examined and information regarding patient and tumor characteristics, clinical presentation, interventions, and survival were tabulated. RESULTS: The average age of patient in our series was 67.5 years. There was a 2.7:1 female to male preponderance. Thirteen (60%) patients presented with thyroid nodule(s). Eleven (50%) presented with aerodigestive tract obstructive symptoms. Sixteen (73%) patients had no pre-existing history of thyroid disease; none had known pre-existing Hashimotos thyroiditis. CONCLUSIONS: The typical thyroid lymphoma patient is female and elderly with painless thyroid enlargement. Compressive symptoms of the aerodigestive tract are common at presentation and may require urgent intervention. Treatment modalities (XRT, CHOP chemotherapy) and outcomes are distinct from other thyroid malignancies. EBM RATING: C

The pattern of myometrial invasion as a predictor of lymph node metastasis or extrauterine disease in low-grade endometrial carcinoma.

The purpose of this study was to examine predictors of lymph node (LN) metastases or extrauterine disease (ED) in low-grade (FIGO grade 1 or 2) endometrioid carcinoma (LGEC) in a multi-institutional setting. For LGEC with and without LN metastasis or ED, each of the 9 participating institutions evaluated patients’ age, tumor size, myometrial invasion (MI), FIGO grade, % solid component, the presence or absence of papillary architecture, microcystic, elongated, and fragmented glands (MELF), single-cell/cell-cluster invasion (SCI), lymphovascular invasion (LVI), lower uterine segment (LUS) and cervical stromal (CX) involvement, and numbers of pelvic and para-aortic LNs sampled. A total of 304 cases were reviewed: LN+ or ED+, 96; LN−/ED−, 208. Patients’ ages ranged from 23 to 91 years (median 61 y). Table 1 summarizes the histopathologic variables that were noted for the LN+ or ED+ group: tumor size ≥2 cm, 93/96 (97%); MI>50%, 54/96 (56%); MELF, 67/96 (70%); SCI, 33/96 (34%); LVI, 79/96 (82%); >20% solid, 65/96 (68%); papillary architecture present, 68/96 (72%); LUS involved, 64/96 (67%); and CX involved, 41/96 (43%). For the LN−/ED− group, the results were as follows: tumor size ≥2 cm, 152/208 (73%); MI>50%, 56/208 (27%); MELF, 79/208 (38%); SCI, 19/208 (9%); LVI, 56/208 (27%); >20% solid, 160/208 (77%); papillary architecture present, 122/208 (59%); LUS involved, 77/208 (37%); CX involved, 24/208 (12%). There was no evidence of a difference in the number of pelvic or para-aortic LNs sampled between groups (P=0.9 and 0.1, respectively). After multivariate analysis, the depth of MI, CX involvement, LVI, and SCI emerged as significant predictors of advanced-stage disease. Although univariate analysis pointed to LUS involvement, MELF pattern of invasion, and papillary architecture as possible predictors of advanced-stage disease, these were not shown to be significant by multivariate analysis. This study validates MI, CX involvement, and LVI as significant predictors of LN+ or ED+. The association of SCI pattern with advanced-stage LGEC is a novel finding.

Acute renal failure secondary to solid tumor renal metastases: Cases report and review of the literature

Renal metastases from solid tumors to both kidneys rarely result in acute renal failure (ARF). We present a case of squamous cell pulmonary carcinoma responsible for ARF due to (1) extensive (50% to 75%) bilateral parenchymal infiltration and replacement accompanied by tissue destruction, (2) widespread vascular invasion and thrombosis resulting in ischemia, and (3) histological evidence for foci of distal intratubular obstruction and pyelonephritis. Five additional cases, including one pulmonary cancer, causing ARF from extensive tissue replacement and destruction are reviewed. In a separate case, ARF resulted from lymphatic metastases rather than from parenchymal destruction or obstruction. Common findings in all six reported cases include bilaterally enlarged kidneys and progressive oligoanuria despite correction of prerenal or postrenal conditions. In our patient and in one other prior reported case, extrarenal obstruction was not considered important because invasive therapeutic procedures were unsuccessful in reversing ARF. In one case, irradiation of kidney tumor resulted in reversal of ARF. These cases emphasize the rare potential for solid tumors to metastasize to both kidneys and result in irreversible oligoanuric ARF. A high level of suspicion is required, and an early diagnosis may result in reversible ARF if the tumor is amenable to chemotherapy or irradiation.

CD10‐positive myxofibrosarcomas: a pitfall in the differential diagnosis of atypical fibroxanthoma

CD10 is now commonly used to differentiate atypical fibroxanthoma (AFX) from melanoma, spindle cell and dedifferentiated variants of squamous cell carcinoma and leiomyosarcoma. However, we have encountered CD10‐positive tumors that mimicked AFX but proved to be myxofibrosarcomas. The purpose of this study was to evaluate CD10 expression in a wide range of mesenchymal neoplasms that may involve the skin using tissue microarrays. Our results indicate that in addition to AFX, CD10 expression is common in myxofibrosarcomas, undifferentiated pleomorphic sarcomas, dermatofibromas and dermatofibrosarcoma protuberans. Myxofibrosarcomas commonly present in the skin and may be difficult to distinguish from AFX on small biopsies and CD10 positivity may confound the diagnostic difficulty.

EXPRESSION OF EPIDERMAL GROWTH FACTOR AND PLATELET-DERIVED GROWTH FACTOR RECEPTORS DURING CERVICAL CARCINOGENESIS

SummaryAltered expression of epidermal growth factor receptor (EGFR) is common in a variety of epithelial malignancies, including cervical cancer. However, the prognostic significance of EGFR expression is controversial for cervical cancer. Platelet-derived growth factor receptor (PDGFR) expression status is unknown in cervical cancer. Our results demonstrated that expression of EGFR and PDGFR was greatly enhanced in vivo and in organotypic cultures of low-grade cervical dysplastic tissues, but levels were decreased in high-grade lesions. To our knowledge, this is the first report identifying the expression of PDGFR in human epithelium. When low-grade dysplastic organotypic culture tissues were induced to differentiate more completely, EGFR expression, but not PDGFR expression, was relocalized to the basal layer as seen in normal tissues. Differentiation also induced phosphorylation of EGFR but not PDGFR. Our results suggest a role for EGFR and PDGFR during the early stages of cervical carcinogensis, and demonstrate the facility of organotypic cultures to study the role of these growth factors in the development of cervical cancer.

Case report 704

A case of extraskeletal osteosarcoma occurring in its most common location, the thigh, is reported. Particular emphasis is given to demonstrating the spectrum of radiological findings, including CT, MRI, and scintigraphy and to illustrate that this entity can metastasize to bone.

Well-differentiated serous ovarian carcinoma presenting as a breast mass: a case report and flow cytometric DNA study.

Ovarian carcinoma metastatic to the breast is uncommon. We report a rare occurrence of ovarian carcinoma that initially presented as a breast mass. Complete examination revealed bilateral ovarian tumors with widespread peritoneal and abdominal disease. One of the ovarian tumors was a papillary serous tumor of low malignant potential, and the other was a well-differentiated papillary serous carcinoma. Although the neoplasm within the breast resembled serous ovarian carcinoma with psammoma bodies, the initial presentation and the presence of an apparent intraductal component created a potential for its misdiagnosis as a primary breast carcinoma. Using DNA flow cytometry, we demonstrated the relationship between the breast, lymph node, and peritoneal metastases and the serous carcinoma, thereby supporting the histologic diagnoses.

Risk factors for recurrence and prognosis of low-grade endometrial adenocarcinoma; Vaginal versus other sites

Endometrial adenocarcinoma is the most common gynecologic cancer in the United States. The prognosis is generally favorable, however, a significant number of patients do develop local or distant recurrence. The most common site of recurrence is vaginal. Our aim was to better characterize patients with vaginal recurrence of low-grade endometrioid adenocarcinoma with respect to associated tumor parameters and clinical outcome. We compiled 255 cases of low-grade (FIGO Grade I or II) endometrioid adenocarcinoma on hysterectomy specimens with lymph node dissection. A total of 113 cases with positive lymph nodes or recurrent disease were included in our study group. Seventy-three cases (13 Grade 1, 60 Grade 2) developed extravaginal recurrence and 40 cases (7 Grade 1, 33 Grade 2) developed vaginal recurrence. We evaluated numerous tumor parameters including: percentage myoinvasion, presence of microcystic, elongated, and fragmented pattern of myoinvasion, lymphovascular space invasion, and cervical involvement. Clinical follow-up showed that 30% (34/113) of all patients with recurrent disease died as a result of their disease during our follow-up period, including 31 (42.5%) with extravaginal recurrence and 3 (7.5%) with primary vaginal recurrence (P=0.001). The 3 patients with vaginal recurrence developed subsequent extravaginal recurrence before death. Vaginal recurrence patients show increased cervical involvement by tumor, but lack other risk factors associated with recurrent disease at other sites. There were no deaths among patients with isolated vaginal recurrence, suggesting that vaginal recurrence is not a marker of aggressive tumor biology.

Pulmonary Crystal-Storing Histiocytosis Diagnosed By Computed Tomography-Guided Fine-Needle Aspiration

Crystal‐storing histiocytosis (CSH) is a rare process most often occurring in conjunction with an underlying hematopoietic neoplasm, usually multiple myeloma or low‐grade B‐cell lymphoma. We report the first case of pulmonary CSH diagnosed by fine‐needle aspiration biopsy. A patient with a history of urothelial carcinoma developed a lung nodule, which was evaluated by fine‐needle aspiration biopsy. Cytologic examination revealed macrophages with abundant cytoplasmic crystals diagnostic of CSH. Based on this cytologic interpretation, additional clinical laboratory evaluation was pursued and revealed a previously unknown monoclonal serum protein. CSH must be differentiated from other non‐neoplastic and neoplastic lesions and when diagnosed, should trigger a search for an underlying lymphoproliferative disorder. Diagn. Cytopathol. 2010.