Umesh Kapur

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.

Diagnostic significance of ‘atypia’ in instrumented versus voided urine specimens

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.

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.

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.

Fine‐needle aspiration of the thyroid is a common procedure, with an established role in reducing unnecessary thyroid surgery and identifying neoplasms and malignancies.

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

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.

Inflammatory sarcomatoid carcinoma: A case report and discussion of a malignant tumor with benign appearance

Inflammatory sarcomatoid carcinoma is an aggressive tumor with an unusually benign appearance. We report the case of a 65-year-old man with a history of inoperable poorly differentiated carcinoma of the right lung, for which he had received chemoradiotherapy. A new solitary mass was discovered 4 years later in the left lung on surveillance computed tomography. The patient underwent thoracotomy with a wedge biopsy on which frozen section was performed. The nodule was vaguely granulomatous and associated with a mixed inflammatory infiltrate and a deceptively bland spindle cell proliferation. Results of immunoperoxidase studies, however, showed that the nodule contained neoplastic cells with an epithelial phenotype that were invading the pulmonary vessels. These are features of the rare inflammatory sarcomatoid carcinoma. In contrast to sarcomatoid carcinomas, this case highlights the deceptively benign appearance of inflammatory sarcomatoid carcinoma. This leads us to concur with the recommendation to exercise caution when attempting the diagnosis of apparently benign lesions on intraoperative frozen section in patients with high clinical suspicion of malignancy.

Fine-needle aspiration diagnosis of metastatic urothelial carcinoma: A review

Urothelial carcinoma (UC) is the most common malignant neoplasm of the urinary tract. Metastases of UC are most common in the regional lymph nodes, lungs, liver, bone, and adrenal glands. Fine‐needle aspiration cytology diagnosis of such metastases can be difficult, particularly in the setting of incomplete clinical history or when multiple primary neoplasms may be present. This review focuses on the cytologic features helpful in differentiating UC from its potential mimics, as well as ancillary studies that may be helpful in the distinction. Diagn. Cytopathol. 2012;.

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.

Giardia lamblia trophozoites in an ultrasound-guided fine-needle aspiration of a pancreatic mucinous neoplasm

The patient is a 74-year-old woman who was found to be in atrial fibrillation and admitted to the hospital. During her hospital stay, a chest radiograph demonstrated an illdefined nodule in the liver. A CT scan revealed three liver lesions ranging from 2.1 to 3.3 cm, typical for hemangiomas, and a 2.7-cm well-defined cystic lesion in the body of the pancreas. The patient underwent upper gastrointestinal endoscopy with ultrasound-guided fine-needle aspiration (EUS-FNA). The aspirated material was used to make direct smears and the needle rinse was placed in CytoLyt for cell block preparation. The cyst fluid was sent for amylase and CEA levels. The slides of both cysts were hypocellular with rare mucinous epithelial cells (Fig. C-1). There were numerous binucleate organisms ranging in size from 9 to 20 lm with a central axostyle, morphologically consistent with the trophozoites of G. lamblia (Fig. C-2). No organisms or mucinous epithelial cells were identified in the cell block. The pancreatic cyst fluid had an amylase level of 100 U/l and a CEA level of 37,749 ng/ml. These values supported the diagnosis of mucinous neoplasm. The patient underwent a distal pancreatectomy that showed a mucinous cystic neoplasm. No organisms were identified in the pancreatic cysts; however, the patient had received 3 days of treatment with metronidazole prior to surgery.

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.