Yimin Ge

Thyrolipoma and thyrolipomatosis: 5 case reports and historical review of the literature.

Because thyrolipoma (adenolipoma of thyroid) and thyrolipomatosis (diffuse lipomatosis of thyroid) are distinctively rare conditions with only few cases reported in the literature, we are reporting 5 additional cases. All the 5 patients were adult females, with ages from 38 to 79 years, who presented with thyroid masses. Four of the patients had normal thyroid function tests and one had mild hypothyroidism. All patients received partial or total thyroidectomy. The thyroid specimens showed either circumscribed yellow-tan masses (cases 1, 2, and 3) or diffuse yellow-brown discoloration (cases 4 and 5). Histologic examination revealed abundant mature fat infiltrating the affected thyroid tissue in 3 distinct patterns: (1) fat infiltration limited to follicular adenomas (thyrolipoma); (2) fat diffusely infiltrating throughout the thyroid gland (thyrolipomatosis); or (3) fat infiltration involving both follicular adenoma and their surrounding thyroid tissue. Because of the rarity of thyroid fat-containing lesions, confusion in differential diagnosis may occasionally occur. It is important to be aware during frozen section that these lesions may present as extrathyroidal nodules, which can be radioactive on intraoperative scan for parathyroid glands. In addition, a papillary thyroid carcinoma was also identified in one case of thyrolipomatosis. All patients recovered well after surgery and there has been no recurrence of the lesions after 1 to 24 years of clinical follow-up. In summary, we are reporting 5 rare cases of thyrolipoma and thyrolipomatosis with distinct histologic patterns. Previously reported cases of thyrolipomatosis were reviewed and analyzed with the current cases.

Clinicopathologic and immunohistochemical characteristics of adult primary cardiac angiosarcomas: analysis of 10 cases

Primary cardiac angiosarcoma is a rare but the most common malignant neoplasm of the heart in adults. The objective of this study is to analyze the clinicopathologic characteristics of primary cardiac angiosarcoma. Ten cases of primary cardiac angiosarcoma treated in a single institution were analyzed for their clinical, pathologic, and immunohistochemical features. There were 6 men and 4 women, with a mean age of 40 years (range, 20-61 years). The patients commonly presented with dyspnea and distant metastasis. All tumors were located in the right atrium, with a mean tumor size of 6.8 cm. Tumors were hemorrhagic, with variegated tan-brown solid areas. Histologically, they exhibited high-grade morphology with mixed solid growth and anatomizing channels. Frequent mitoses and tumor necrosis were common. The tumors were strongly positive for CD31, CD34, FLI-1, and WT-1 but negative for AE1/3, D2-40, human herpesvirus 8, and epidermal growth factor receptor. The tumor cells were focally reactive to p53, with a high rate of Ki-67 expression. A complete tumor resection was not possible in any of the patients because of the size or extensive local invasion of the tumor. Overall survival ranged from 1 to 81 months (mean, 26.6 months) after initial histologic diagnosis. Primary cardiac angiosarcomas are rare tumors that commonly arise in the right atrium. The mean age is much younger than that of soft tissue angiosarcoma. Regional tumor extension and distant metastasis are extremely common at the time of diagnosis. Surgical resection with adjuvant chemotherapy is currently the preferred treatment, and survival time appears to be inversely correlated with the tumor size and degree of regional tumor extension at the time of surgery.

Clinical performance of the Food and Drug Administration-Approved high-risk HPV test for the detection of high-grade cervicovaginal lesions.

In recent years, high‐risk human papillomavirus (hrHPV) testing for triaging atypical squamous cells of undetermined significance and cotesting with cytology have been implemented in clinical practice. However, clinical data for primary screening with human papillomavirus (HPV) testing alone are currently lacking.

Unexpected high prevalence of HPV 90 infection in an underserved population: is it really a low-risk genotype?

CONTEXT Human papillomavirus 90 (HPV 90) is a rarely reported genotype worldwide, with few data available to characterize its prevalence, distribution, and disease association. OBJECTIVE To investigate the prevalence, distribution, and disease association of HPV 90 infection in an underserved inner-city Latino population. DESIGN Residual SurePath specimens were collected from 808 women referred for abnormal Papanicolaou tests. DNA microarray against HPV subtypes determined HPV genotypes, followed by confirmatory DNA sequencing assays. RESULTS HPV 90 was detected in 32 women (4%) with an average age of 39 years (range, 23-42 years). Most women (31 of 32) had only HPV 90 infection, and one woman was coinfected with HPV 13. Two women had low-grade intraepithelial lesion and one woman had low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion; the rest of the women had negative concurrent cytology. Available concurrent biopsies in 2 of 3 instances with abnormal cytology confirmed HPV cytopathic effect, with no high-risk HPV detected by in situ hybridization. CONCLUSIONS We demonstrated an unexpected, high infection rate of HPV 90 in an underserved population in the United States, with 9.4% having concurrent cytologic abnormalities. In the absence of other detectable HPV genotypes by DNA microarray, DNA sequencing, and in situ hybridization, we suspect HPV 90 may be a causative agent responsible for the concurrent cervical lesions. Because of potential shifts in HPV infection patterns in the postvaccine era, monitoring the emergence of previously underrecognized HPV genotypes is becoming increasingly important. To the best of our knowledge, this is the first study to characterize HPV 90 infection in an underserved, North American population.

Double lung transplantation for diffuse idiopathic pulmonary neuroendocrine cell hyperplasia.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare cause of obstructive lung disease and a proposed precursor of pulmonary carcinoid tumors. With increased awareness of this disease, an accumulating number of cases have been reported. Patients may have progressive shortness of breath due to small airway obstruction. There is limited information on treatment of the disease, particularly for those with progressive disease. Here we report 2 patients who were treated at our institution with double lung transplantation. Both patients were female nonsmokers with a clinical presentation of cough and dyspnea. Multiple bilateral lung nodules were identified on high-resolution computed tomography and pulmonary function tests showed obstructive pattern in both patients. The diagnoses of DIPNECH were made by histologic evaluation of the explanted native lungs. These 2 patients are in stable condition following double lung transplantation at the time of this report. DIPNECH is increasingly recognized due to improved sensitivity of investigative imaging and increased awareness of the entity. Considering the malignant potential and lack of effective treatment of the disease, lung transplantation could be potentially an effective treatment option for these patients.

Image-guided ThinPrep Papanicolaou tests and cotesting with high-risk human papillomavirus in women aged 30 years and older in a low-risk private practice population

Screening for cervical cancer precursors has evolved considerably with the introduction of new technologies to improve the early detection of disease. The objective of this study was to analyze the accuracy and effectiveness of combined screening with cytology and high‐risk human papillomavirus (HR‐HPV) testing in a low‐risk population of women aged ≥30 years.

The Presence of Anti-HLA Donor-Specific Antibodies in Lung Allograft Recipients Does Not Correlate With C4d Immunofluorescence in Transbronchial Biopsy Specimens

CONTEXT C4d immunofluorescence (IF) is a surrogate for development of donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) class I and II antigens in kidney and heart biopsy specimens for monitoring of antibody-mediated (humoral) allograft rejection (AMR). Use of C4d IF in monitoring of lung allografts has shown conflicting results. OBJECTIVE To determine if C4d IF can be used as a reliable marker for AMR and if it correlates with the presence of DSAs and histologic findings on biopsy. DESIGN All transbronchial biopsies in lung allograft recipients, performed at our institution in a 3-year period, were reviewed. A cohort of 92 patients with 110 corresponding biopsies met the inclusion criteria of (1) having a resulted DSA within 2 weeks of biopsy and (2) having C4d immunofluorescence studies performed and confirmed. RESULTS Twenty-nine patients (31.5%) were positive for DSAs and 63 patients (68.5%) did not develop DSAs. Positive C4d capillary IF was seen in 18 of 110 total biopsy specimens (16.4%). Eight of these biopsy samples were from patients positive for DSAs and 10 were from patients negative for DSAs. The correlation coefficient between the presence of DSAs and C4d IF was 0.1628 (P = .09). CONCLUSIONS A significant proportion of DSA-positive patients had negative C4d IF results and frequently have no histologic changes on biopsy specimens. DSA-negative patients can be positive for C4d and may show the same histologic changes as reported for DSA-positive patients. Diagnosis of AMR in lung may require a collaborative approach combining clinical data, DSA status, and histology.

Interstitial cystitis: Another IgG4-related inflammatory disease?

Interstitial cystitis (IC) is a disease of undetermined etiology and pathogenesis. Inflammation is thought to play a key role in many patients, characteristically with an increase in mast cells within the detrusor muscle of the bladder. We observed that some patients with IC had prominent plasma cells in bladder tissue, which elicited our interest in their possible pathogenic role in patients with IC. A total of 44 cases of IC were collected, including 42 bladder biopsies and 2 cystectomies. Patient age ranged from 18 to 92 years (average age of 49.5 years) and included 7 male and 37 female patients. The histology and immunostains for IgG, IgG4 and tryptase were examined, and the results were correlated with clinical and cystoscopic findings. Four cases showed a significant increase in IgG4-positive plasma cells, with greater than 30 IgG4 plasma cells per high-power field and an IgG4/IgG ratio greater than 0.5. In addition, statistically significant differences were found between IC with IgG4-positive plasma cells vs IgG4-negative cases. The IgG4-positive patients were of older age and had increased severe inflammation and decreased bladder capacity as compared with the IgG4-negative patients. We propose that a subset of patients with IC may have an IgG4-related disease, and further study including serum IgG4 measurement is required to better define this relationship.

p16INK4a and ProEx C Immunostains Facilitate Differential Diagnosis of Hyperchromatic Crowded Groups in Liquid-Based Papanicolaou Tests with Menstrual Contamination

Objective: Evaluation of hyperchromatic crowded groups in Papanicolaou (Pap) tests from women during menstruation can be a diagnostic pitfall due to similar morphological appearances with significant cervical lesions. We studied the results of p16INK4a and ProEx C on cell blocks from Pap tests during menstruation in an attempt to facilitate the differentiation. Study Design: Immunohistochemical stains for p16INK4a and ProEx C were performed on 25 cell blocks prepared from residual liquid-based cervical material with menstrual contamination. Results: Strong, diffuse, and full thickness staining pattern for p16INK4a and ProEx C was observed in cases of high-grade squamous intraepithelial lesion (HSIL) and small cell carcinoma of the cervix. The low-grade squamous intraepithelial lesion cases and cases negative for intraepithelial lesion or malignancy were negative for ProEx C, with focal staining for p16INK4a. The benign endometrial cells had either negative or focal patchy staining, which is often associated with tubal metaplasia. Conclusion: p16INK4a and ProEx C are sensitive markers for identifying significant lesions in Pap test specimens with menstrual contamination. Patchy/mosaic staining may be seen in benign endometrial tissue with tubal metaplasia, but strong, diffuse staining likely indicates HSIL or carcinoma. These findings can be helpful in interpreting hyperchromatic crowded groups in menstrual Pap specimens. Further study may be prudent, being aware of the small study group.

Folate Receptor α Expression Level Correlates With Histologic Grade in Lung Adenocarcinoma

CONTEXT -Folate receptor α (FRA) is a glycosylphosphatidylinositol-anchored high-affinity folate receptor that localizes to the apical surface of epithelia when it is expressed in normal tissue. Unlike normal tissues, FRA may localize to the basolateral side in tumors. These features make FRA an attractive drug target, and several FRA-targeted drugs have been developed and are in phases of clinical testing. Folate receptor α protein expression shows intertumoral variability that may correlate with response to therapy and to clinicopathologic parameters. Using immunohistochemistry, a recent study of breast carcinomas found FRA protein expression was associated with triple-negative status and high histologic grade in breast cancer. Although a prior study of lung adenocarcinomas found the expression level of the gene encoding FRA, FOLR1, was significantly increased in low-histologic-grade tumors compared to high-histologic-grade tumors, the relationship between FRA protein expression and histologic grade has not been reported for lung adenocarcinomas. OBJECTIVE -To investigate the relationship between FRA protein expression level and clinicopathologic parameters in lung adenocarcinomas, including histologic grade, by performing immunohistochemistry for FRA on a cohort of non-small cell lung carcinomas. DESIGN -High-density tissue microarrays constructed from 188 non-small cell lung carcinomas and used in prior studies were immunostained with FRA-specific antibody clone 26B3. Folate receptor α membranous staining intensity was given a semiquantitative score from 0 to 3+ for triplicate cores of tumor and averaged for each tumor. An average semiquantitative score from 0 to 1.4 was considered low expression, and an average semiquantitative score greater than 1.4 was considered high expression. RESULTS -The majority (60 of 78; 77%) of lung adenocarcinomas and a minority (4 of 41; 10%) of lung squamous cell carcinomas were positive for FRA. Folate receptor α expression in lung adenocarcinomas compared with squamous cell carcinomas was statistically different (P < .001, χ(2) test). In lung adenocarcinomas, FRA expression level correlated with histologic grade (P = .005, χ(2) test for trend), but no other clinicopathologic parameter. The majority (23 of 27; 85%) of grade 1 adenocarcinomas had high FRA protein expression, whereas approximately half of grade 2 (10 of 19; 53%) and grade 3 (12 of 25; 48%) adenocarcinomas had high FRA protein expression. Out of adenocarcinomas with lepidic growth pattern, 16 of 20 (80%) showed high FRA protein expression. Out of adenocarcinomas with solid growth pattern, 2 of 6 (33%) showed high FRA protein expression. In lung adenocarcinomas, FRA expression level did not correlate with thyroid transcription factor 1, napsin A, or survival. CONCLUSIONS -Folate receptor α protein was expressed in the majority of lung adenocarcinomas and a minority of lung squamous cell carcinomas. Folate receptor α protein expression correlated with histologic grade for lung adenocarcinomas, and the greatest difference was observed between grade 1 and grade 3. Our results indicate that poorly differentiated adenocarcinomas or focuses of poor differentiation in a heterogeneous tumor may lack FRA protein expression and be more likely to be resistant to FRA-targeting drugs.