Robot-Assisted Laparoscopic Adrenalectomy for Rare Myxoid Adrenocortical Carcinoma.

BACKGROUND: Surgical resection remains the standard treatment for adrenocortical carcinoma. Higher rates of local and peritoneal recurrence have been reported with the laparoscopic approach compared to open resection, although the evidence is limited. A dilemma occurs when tumors appear benign in nature, measure >5 cm, or when patients request a minimally invasive surgical approach. We describe the first reported case to date of successful robot-assisted laparoscopic adrenalectomy for myxoid variant adrenocortical carcinoma. CASE PRESENTATION: A 38 year old female presented with a large 8.0 cm enhancing left adrenal mass concerning for pheochromocytoma, given refractory hypertension and symptoms of palpitations and headaches. Functional work up was negative. The patient underwent robot-assisted laparoscopic left adrenalectomy after appropriate alpha and beta blockade. Histological sections demonstrated a cortical neoplasm with prominent myxoid changes consistent with myxoid adrenocortical carcinoma. The patient's symptoms resolved and serial imaging demonstrated no recurrence three and nine months, post-operatively. CONCLUSION: Myxoid adrenocortical carcinoma is a rare and aggressive entity best managed with surgical resection. Though open resection for invasive adrenal cancer remains the gold standard, minimally invasive approaches are being increasingly used, whether deliberately or not. We describe the first reported robot-assisted laparoscopic adrenalectomy for invasive myxoid adrenocortical carcinoma.

Thyroid fine-needle aspiration cytology: performance data of neoplastic and malignant cases as identified from 1558 responses in the ASCP Non-GYN Assessment program thyroid fine-needle performance data.

BACKGROUND: Fine-needle aspiration of the thyroid is a common procedure, with an established role in reducing unnecessary thyroid surgery and identifying neoplasms and malignancies. METHODS: The study evaluated 1558 responses in the American Society for Clinical Pathology (ASCP) Non-GYN Assessment program of aspirates of thyroid neoplasms and malignancies and placed them into the following groups: group A (target or correct interpretation), group B (incorrect interpretation as a benign thyroid nodule), group C (incorrect interpretation malignant aspirate as thyroid neoplasm), and group D (malignant diagnosis with incorrect interpretation). In clinical practice, responses in groups A, C, and D would lead to surgical excision, whereas responses in group B would not. RESULTS: Of a total of 1558 responses, 78.5% of the responses were in group A, 8.5% in group B, 3.75% in group C, and 9.25% in group D. By individual diagnosis, the group rates were 86.5%, 0%, 11%, and 2.5% for anaplastic thyroid carcinoma; 83%, 5.5%, 4.25%, and 7.25% for papillary thyroid carcinoma; 79%, 7%, 6%, and 8% for medullary thyroid carcinoma; 83.5% 6.75%, 0%, and 9.75% for Hürthle cell neoplasm; and 61%, 22%, 0%, and 17% for follicular neoplasm in groups A, B, C, and D respectively. CONCLUSIONS: Fine-needle aspiration was effective in diagnosing thyroid neoplasms and malignancies and in separating thyroid nodules into surgical and nonsurgical categories. Data from a large group of cytology professionals showed good performance; however, there is room for improvement, especially in making specific diagnoses. In particular, follicular neoplasm and follicular variant of papillary thyroid carcinoma were challenging diagnoses for participants.

Cytologic and cystoscopic predictors of recurrence and progression in patients with low-grade urothelial carcinoma.

BACKGROUND: Patients with low-grade urothelial carcinoma (LGUC) are at risk of recurrence and must undergo lifelong surveillance. To date, cytology and cystoscopy are the gold standard for the detection of de novo and recurrent LGUC. The objective of the current study was is to further characterize the role of cytology and cystoscopy in determining the risk of recurrence and progression in these patients. METHODS: The authors retrospectively identified patients with LGUC who had urine cytology within 2 months of biopsy, and data were abstracted from their electronic charts. Electronic medical records were reviewed for cystoscopic findings and histologic and cytologic follow-up data over a 5-year period. Statistical analysis was performed with chi-square tests. RESULTS: In total, 76 patients were identified who had histologic follow-up material available, and 49% of those patients demonstrated progression or recurrence of urothelial carcinoma. The initial presence of multiple lesions on cystoscopy was associated with any recurrence or progression (67.7% vs 31%; P = .002), tumor size >2 cm was associated with initial positive or suspicious urine cytology (23.8% vs 3.7%; P = .076), and positive or suspicious initial cytology was associated with high-grade recurrence (58.3% vs 19.4%; P = .009). CONCLUSIONS: Cystoscopic findings, such as the presence of multiple lesions, together with concurrent positive or suspicious urine cytology, were associated with recurrence or progression of LGUC. These findings may help to identify high-risk patients.

Development of cerebral metastasis after medical and surgical treatment of anal squamous cell carcinoma.

Squamous cell carcinoma of the anus is a relatively uncommon GI malignancy. When it does occur, it metastasizes in only a small minority of patients. Spread of anal squamous cell carcinoma to the brain is exceedingly rare, and has been previously reported only three times in the medical literature. We report the case of a 67 year old male who was diagnosed on presentation with a poorly differentiated anal squamous cell carcinoma that already had a solitary metastasis to the liver. While the tumors were initially responsive to chemoradiotherapy, the patient's primary and liver lesions recurred. The patient then underwent synchronous abdominoperineal resection for the primary lesion and a liver lobectomy for the metastasis. Soon thereafter, the patient developed focal neurologic symptoms and was found to have an intracranial lesion that on biopsy demonstrated metastatic squamous cell carcinoma. This case highlights the fact that patients with a previous history of anal squamous cell carcinoma can occasionally develop cerebral metastasis. Furthermore, cerebral metastases from anal squamous cell carcinoma portend a dismal prognosis even in the face of aggressive medical and surgical therapy.

Dysplastic squamous cells are frequently present in urine cytology specimens of patients with high-grade urothelial carcinoma.

BACKGROUND: In urothelial carcinoma (UCA), squamous differentiation (SqD) occurs mainly in high-grade UCA with invasion. Therefore, we sought to determine the frequency of dysplastic squamous cells (DSC) in urine specimens obtained from patients with high-grade UCA asking if DSC could serve as a surrogate marker for high-grade UCA. DESIGN: We searched for cases with a histologic diagnosis of high-grade UCA and available concurrent cytology, yielding 93 surgical specimens (including 71 biopsies, 12 cystectomies, 5 nephrectomies, 4 ureterectomies, and 1 urethrectomy) from 68 patients with 98 urine cytology samples. Both cytology and histologic specimens were evaluated for the presence of any SqD on histology and the presence of DSC on cytology besides urothelial cells. RESULTS: Forty-three of 68 patients (63%) had a cytologic diagnosis of 'positive/suspicious'. Twenty-one patients (30%) had surgical specimens that showed SqD. Seventeen patients had urine cytology specimens showing DSC (25%). Thirteen of these 17 patients showed DSC with concurrent malignant urothelial cells, while 4 patients displayed only isolated DSC. CONCLUSION: SqD is common in patients with high-grade UCA. DSC were detected in a subset of specimens from patients with high-grade UCA. In some instances, isolated DSC on cytology may represent the only evidence of an unsampled high-grade malignancy.

Utility of p16, Ki-67, and HPV test in diagnosis of cervical intraepithelial neoplasia and atrophy in women older than 50 years with 3- to 7-year follow-up.

BACKGROUND: Differentiating cervical intraepithelial neoplasia (CIN) from atrophy in postmenopausal women based on morphology alone is challenging. p16 and Ki-67 help distinguish CIN2/3 from atrophy. The goal of this study is to further characterize the utility of p16, Ki-67, and human papillomavirus (HPV) tests in women older than 50 years, particularly in CIN1. DESIGN: The authors retrospectively identified cervical specimens from three, 1-year time periods. Included were cases from women older than 50 years with benign diagnoses, atrophy, and CIN. Slides were stained with p16 and Ki-67 and graded as positive or negative. Medical records were reviewed for cytology, HPV test, and histopathologic diagnoses from the time of biopsy to 2010. RESULTS: A total of 97 cervical samples were included. In all, 34 (74%) CIN1 cases were negative for p16 and Ki-67. Of CIN1 cases with positive HPV tests, only 1/10 (10%) had positive p16 staining versus 2/2 (100%) of CIN2/3 cases. Of 39 women with CIN1 who had follow-up data available, 4 (10%) had subsequent histologic progression to CIN2/3 and none developed invasive disease. CONCLUSIONS: In our study, the majority of cases (74%) diagnosed as CIN1 in women ≥ 50 years are negative for p16 and Ki-67 and do not progress to high-grade dysplasia during 3- to 7-year follow-up. A combination of morphology, p16, and Ki-67 on cervical specimens in women older than 50 years, and furthermore, use of these stains on Pap tests in combination with HPV testing may help distinguish CIN from atrophy and reduce unnecessary invasive follow-up testing.

Diagnostic significance of 'atypia' in instrumented versus voided urine specimens.

BACKGROUND: Urine cytology plays an important role in monitoring patients with a history of urothelial carcinoma. Because it is difficult to reliably discriminate artifacts induced by instrumentation, inflammation, or therapy those of from malignant cells, many of these specimens are categorized as atypical. The objective of the current study was to study the prevalence and significance of atypical urine cytology with regard to the effect of instrumentation and prior biopsy. METHODS: All urine cytology cases seen during a 4-year period (2001-2004) with a diagnosis of atypical urothelial cells (AU) were obtained from the cytopathology computer database. In all cases with available surgical follow-up, the following data were extracted: total number and type of urine specimen, the primary histologic diagnosis, and follow-up histologic diagnosis. RESULTS: In all, 1653 voided and 3502 instrumented urine specimens were examined. A diagnosis of AU was rendered in 115 (6.9%) of the voided urine specimens and in 277 (7.9%) of the instrumented specimens. Follow-up histology was available in 70 cases, including 55 instrumented and 15 voided urine specimens. A nonbenign follow-up diagnosis was observed in 18 of 55 (32.7%) cases in the instrumented group and in 7 of 15 (46.6%) cases in the voided group. Voided urine was marginally associated with a worse subsequent biopsy diagnosis (Pexact Monte Carlo = .09) CONCLUSIONS: An AU diagnosis is more predictive of a subsequent adverse biopsy diagnosis in voided urine specimens compared with instrumented urines. In the absence of a benchmark for the atypia rate, it is prudent to keep the atypia rate low to keep it more meaningful. This important category should be used by the pathologist to convey concern and recognize the difficulty in interpretation of specimens that may require close follow-up.

Use of digital video for documentation of microscopic features of tissue samples.

CONTEXT: Digital photography is commonly used to document microscopic features of tissue samples, but it relies on the capture of arbitrarily selected representative areas. Current technologic advances permit the review of an entire sample, some even replicating the use of a microscope. OBJECTIVE: To demonstrate the applicability of digital video to the documentation of histologic samples. DESIGN: A Canon Elura MC40 digital camcorder was mounted on a microscope, glass slide-mounted tissue sections were filmed, and the unedited movies were transferred to a Apple Mac Pro computer. Movies were edited using the software iMovie HD, including placement of a time counter and a voice recording. RESULTS: The finished movies can be viewed in computers, incorporated onto DVDs, or placed on a Web site after compression with Flash software. The final movies range, on average, between 2 and 8 minutes, depending on the size of the sample, and between 50 MB and 1.6 GB, depending on the intended means of distribution, with DVDs providing the best image quality. CONCLUSIONS: Digital video is a practical methodology for documentation of entire tissue samples. We propose an affordable method that uses easily available hardware and software and does not require significant computer knowledge. Pathology education can be enhanced by the implementation of digital video technology.

Validation of World Health Organization/International Society of Urologic Pathology 2004 classification schema for bladder urothelial carcinomas using quantitative nuclear morphometry: identification of predictive features using bootstrap method.

OBJECTIVES: Despite the introduction of the new World Health Organization 2004 grading classification, the grading of urothelial carcinoma remains difficult and subjective. The aim of this study was to evaluate the role of computer-assisted image morphometric analysis as a tool to improve the objectivity of histologic grading of urothelial carcinoma. METHODS: A total of 75 urinary bladder biopsies from a cohort of patients with a first-time diagnosis of urothelial carcinoma representing low-grade (n = 19) and high-grade (n = 56) urothelial carcinoma were evaluated. Quantitative nuclear morphometry was performed on these biopsies using approximately 80 to 100 cells per case. A total of 17 nuclear morphometry features were extracted, and a bootstrap-based predictor selection using stepwise logistic regression analysis was performed. Subsequently, a validation was performed using the five top features from the logistic regression analyses by implementing a nonparametric discriminant analysis to identify the most discriminative features that predicted for high-grade cases. RESULTS: The bootstrap technique included nuclear pleomorphism as the most frequently selected predictor of high-grade urothelial carcinoma (in 213 of 500 replicates). Validation using the top five features in the logistic regression analysis method (pleomorphism, configuration run length, DNA mass, feret-Y, and age) using discriminant analysis gave a resubstitution error of 4%, indicating the usefulness of the selected predictors. CONCLUSIONS: The present study is the first to provide a morphometric validation of the World Health Organization 2004 system for pathologic grading of bladder cancer. Furthermore, quantitative nuclear morphometry could aid in the objective grading of urinary bladder biopsies. This information might aid the treating physicians in better risk stratification of patients with urothelial carcinoma.

Pulmonary glomus tumor.

Glomus tumor (GT) is an infrequent but distinct neoplasm. Pulmonary GT is a rare neoplasm with only a few cases reported in the literature. These tumors are usually benign and, although rare, tumors with aggressive behavior have been reported. The tumor size, location, and histomorphological features may be useful in predicting tumor behavior. We present here a case of pulmonary GT that was initially diagnosed as a typical carcinoid tumor. The differential diagnosis as well as the recent classification of GTs is discussed along with a review of literature.

Expanding the pathologic spectrum of immunoglobulin light chain proximal tubulopathy.

CONTEXT: In plasma cell dyscrasias, involvement of the distal tubules is frequent and well characterized. In contrast, proximal tubules have only rarely been reported to show diagnostic pathology such as intracytoplasmic crystals. OBJECTIVE: To look for additional morphologic features that might be helpful in the diagnosis of proximal tubulopathy associated with an underlying plasma cell dyscrasia. DESIGN: We examined patients presenting with nonspecific renal symptoms who were found to have light chain restriction limited to proximal tubular epithelium by immunofluorescence. We correlated these results with light microscopy, electron microscopy, and the clinical findings. RESULTS: By immunofluorescence, 5 patients had light chain restriction in proximal tubular epithelium. By light microscopy, only 1 patient had focal rhomboid crystals in the proximal tubular epithelium; all other biopsies failed to show any discernible pathology within the proximal tubules or elsewhere in the kidney. By electron microscopy, proximal tubules from 2 patients showed crystals with a latticelike structure, whereas the remaining 3 patients had only prominent phagolysosomes. However, by immunoelectron microscopy, the lysosomal content showed light chain restriction (in 2 cases studied). Post-kidney biopsy, all patients were diagnosed with multiple myeloma or plasma cell dyscrasia. One patient developed renal failure and had recurrence of crystals in the allograft. CONCLUSIONS: Light chain proximal tubulopathy may be associated with the presence of crystals or with the presence of phagolysosomes with light chain restriction as the sole abnormality. Both kappa and lambda light chains may be involved. The prognosis is variable and the pathology may recur in transplants.

Follicular neoplasm of the thyroid--vanishing cytologic diagnosis?

The significance of making a diagnosis of follicular neoplasm on fine needle aspiration (FNA) biopsy remains a controversial issue, considering that the diagnosis of follicular carcinoma is based on histological criteria and the significantly decreasing incidence of follicular carcinoma in the general population. On FNA the main differential diagnoses of follicular neoplasm includes follicular variant of papillary carcinoma (FVPC), follicular adenoma, follicular carcinoma and benign solitary nodule occurring in a goiter. Several studies have looked at immunohistochemical and molecular markers to distinguish benign from malignant lesions but none of them have proved to be infallible. Although, FVPC is a distinct entity from the follicular neoplasm group, it is not always possible to separate it from the other follicular lesions because of overlapping cytologic features and often-sporadic presence of nuclear features, follicular variant of papillary carcinoma remains the main pitfall in a diagnosis of follicular neoplasm. Since a significant number of cases that are malignant on follow-up are usually FVPC, consequently, follicular neoplasm is an essential diagnostic consideration on FNA. In addition, follicular carcinoma, despite a decreasing incidence continues to be a real entity. Therefore, it is essential that follicular neoplasm continue to be part of our diagnostic repertoire.

Fine-needle aspiration of malignant mesothelioma with unusual morphologic features: a case report.

Malignant mesothelioma is an aggressive neoplasm linked to asbestos exposure. Most mesothelioma patients present with pleural effusion and the fluid is typically sent for cytological examination. Therefore, cytopathologists are most familiar with features of mesothelioma in fluid preparations. We present here a case of malignant mesothelioma with unusual cytological features diagnosed on FNA. The diagnosis was confirmed by immuno-histochemical and electron microscopic studies. In addition, we compare the cytomorphological features observed in malignant effusion versus fine-needle aspiration.

Prediction of nonsentinel lymph node metastasis in sentinel node-positive breast carcinoma.

The incidence of nonsentinel (NSN) lymph node metastases in patients with a tumor-positive sentinel (SN) lymph node varies greatly from 20% to 70% in the published literature. Current practice is that most patients with a positive SN (micro- and macrometastases) undergo a complete axillary dissection. However, it has been shown by other investigators that a large number of patients with a positive SN do not necessarily need a complete axillary dissection. In this analysis, we reviewed the pathology slides from 58 patients who had undergone SN and axillary node dissection. The tumor size, histologic parameters, receptor (estrogen and progesterone), and HER-2neu oncoprotein expression were noted. Student t test and Fisher exact test were used for statistical analysis. Of 58 patients, 19 (32.7%) had NSN metastases. Primary tumor size (P < .002), size of SN metastatic tumor (P < .03), and the presence of extracapsular tumor extension (P < .0001) were associated significantly with NSN metastases. We have shown in this study that it would be possible to predict the NSN status based on primary tumor size, size of SN metastatic tumor, and presence of SN extracapsular tumor extension.