David Ben-Dor

Adrenocortical Oncocytic Tumors: Report of 10 Cases and Review of the Literature

Ten additional adrenocortical oncocytic tumors are presented: 2 benign oncocytomas, 4 borderline oncocytomas of uncertain malignant potential, and 4 oncocytic carcinomas. Histologically all tumors were entirely or predominantly composed of oncocytes. Immunohistochemically all tumors were immunoreactive for mitochondrial antigen mES-13. Electron microscopy was performed in 8 cases and was confirmatory of the oncocytic cell change. The morphologic parameters of the Weiss system, considered to be predictive of the biologic behavior of conventional (nononcocytic) adrenocortical tumors, are reviewed in the context of their possible application to the oncocytic tumor variant. Proposed major criteria (high mitotic rate, atypical mitoses, venous invasion) and minor criteria (large size and huge weight, necrosis, capsular invasion, sinusoidal invasion) in distinguishing malignant tumors are discussed, and definitional criteria (predominantly cells with eosinophilic and granular cytoplasm, high nuclear grade, diffuse architectural pattern) in common with all types of oncocytic tumors are outlined. The authors’ proposed working rules for diagnostic categorization of oncocytic adrenocortical tumors are defined, with the presence of 1 major criterion indicating malignancy, 1 to 4 minor criteria indicating uncertain malignant potential (borderline), and the absence of all major and minor criteria indicative of benignancy. Using these criteria, the diagnosis of malignancy was straightforward in 3 of the 4 cases designated as oncocytic carcinoma (presence of at least 2 major criteria and all the minor criteria), while in 1 case the original diagnosis of benign oncocytoma was reversed to malignant following critical review of the original pathologic material after local tumor recurrence. Tumor recurrence occurred in 2 carcinomas at 8 and 20 months, respectively, and was followed in 1 case by the patient’s death. The third patient expired at 6 months from unrelated causes, and the fourth patient is free of disease at the relatively short follow-up interval of 6 months. Regarding the 4 patients with borderline tumors, all are alive with no evidence of disease, with follow-up ranging from 10 to 61 months (mean 38.7 months). The 2 benign tumors have a follow-up of 25 and 30 months, respectively. Diagnostic difficulties are delineated and a complete review of the literature on this topic has also been performed.

Immunostaining for Human Herpesvirus 8 Latent Nuclear Antigen-1 Helps Distinguish Kaposi Sarcoma From Its Mimickers

We assessed the usefulness of a mouse monoclonal antibody (13B10) against human herpesvirus 8 (HHV-8) latent nuclear antigen-1 (LNA-1) in diagnosis of Kaposi sarcoma (KS) and for distinguishing it from various mimickers by studying 50 cases of KS and 53 mimickers (angiosarcoma, 15; kaposiform hemangioendothelioma, 6; spindle cell hemangioma, 3; reactive angioendotheliomatosis, 3; bacillary angiomatosis, 4; acroangiomatous dematitis, 2; microvenular hemangioma, 2; hobnail hemangioma, 2; pyogenic granuloma, 5; dermatofibroma, 8; arteriovenous hemangioma, 1; verrucous hemangioma, 1; nonspecific vascular proliferation, 1) from patients with or without acquired HIV infection. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections. All 50 cases of KS were positive for HHV-8 LNA-1, with immunolocalization in the nuclei of the spindle cells and cells lining the primitive and thin-walled vascular channels, whereas all 53 mimickers (including 4 lesions from HIV-positive patients) tested negative. The results idicate that positive immunostaining for HHV-8 LNA- 1 exhibits high sensitivity and specificity for the diagnosis of KS and is, thus, useful for distinguishing it from the mimickers.

Plasmacytoid urothelial carcinoma: detailed analysis of morphology with clinicopathologic correlation in 17 cases.

The plasmacytoid variant of urothelial carcinoma is rare, of which less than 40 cases have been reported in the English language literature. Herein we report the largest series to date of 17 cases of urothelial carcinoma with plasmacytoid features and report the associated clinicopathologic findings. The architectural pattern of the tumor varied from cells arranged in cords and single cells (35%), small nests (17%), solid sheetlike growth (29%), and diffuse discohesive patternless architecture (23%). The plasmacytoid component varied from 15% to 100% of the specimen analyzed; in 12 cases the plasmacytoid component composed greater than 50% of the tumor. The individual tumor cells had striking morphologic overlap with plasma cells with an eccentrically placed nucleus and abundant amphophilic to eosinophilic cytoplasm. The nuclei were of low to intermediate nuclear grade with minimal nuclear pleomorphism. Thirteen of 17 cases (76%) were associated with conventional high-grade invasive urothelial carcinoma and 9 cases showed very focal intracytoplasmic vacuoles mimicking signet ring cells. One case also showed sarcomatoid dedifferentiation. The tumor cells were positive for cytokeratin 7 (94%) and cytokeratin 20 (31%); CD138 was positive in 94% of cases. All cases were invasive—7 into at least the lamina propria, 7 into at least the muscularis propria, and 3 into perivesical fat. Follow-up information was available in 16 cases (range: 2 wk to 43 mo; mean 10 mo; median 5.5 mo). Eleven patients died of disease and 5 patients were alive with disease. Plasmacytoid variant of urothelial carcinoma is an aggressive subtype associated with poor prognosis. In limited samples, it may be misdiagnosed as chronic cystitis or plasmacytoma, a pitfall further compounded by CD138 expression. Distinction from metastatic carcinoma from other primary sites such as stomach and breast is critical due to differing therapeutic implications.

Acute prostatitis in middle-aged men: a prospective study

To determine the clinical outcome of middle‐aged men with acute prostatitis, the optimum time for re‐assessing their prostate‐specific antigen (PSA) levels, and to detect any possible echotextural and vascular changes that remain as a consequence of acute inflammation.

Using gray-scale and two different techniques of color Doppler sonography to detect prostate cancer

OBJECTIVES To correlate the findings of prostate color Doppler sonography (CDS) with those of site-specific transrectal ultrasound-guided core biopsy; to evaluate the significance of two different color presets in detecting prostate cancer compared with gray-scale transrectal ultrasonography; and to compare the accuracy of conventional gray-scale transrectal ultrasound (CGS)-guided biopsy with CDS-guided biopsy. METHODS Seventy patients were enrolled in this prospective study. CDS was performed before biopsy. Two color presets were used: CDS-1 (high sensitivity) and CDS-2 (high specificity). The color flow was graded on a scale from 0 to 2+. At the completion of the color grading, color maps were constructed. In each case, CDS-guided biopsy was performed followed by CGS-guided biopsy (six sextant biopsies and focal lesional biopsies). RESULTS The cancer detection rate was 33%, 31%, and 27% for CGS-guided biopsy, CDS-1, and CDS-2, respectively. CDS-1 was more sensitive than CDS-2 (81% versus 60%) but both presets had similar specificities (79% versus 82%). CGS-guided biopsy yielded a sensitivity of 90%, a specificity of 38%, and a positive and negative predictive value of 34% and 83%, respectively. A biopsy strategy combining hypoechoicity with increased color flow increased the specificity to 97%, positive predictive value to 68%, and negative predictive value to 84%, but its sensitivity was low (18%). CONCLUSIONS Our experience suggests that low-velocity, high-sensitivity color is superior to all other CDS settings. The presence of focal peripheral zone hypervascularity at CDS is associated with a high likelihood of prostate cancer. However, only a combination of CDS guidance with six sextant biopsies may achieve maximal sensitivity and specificity.

Oncocytic Adrenocortical Tumors

Oncocytic tumors of the adrenal cortex are very uncommon. Arriving at the correct diagnosis is important and the use of mES-13 immunohistochemical testing or ultrastructural analysis can support their recognition. However, once the diagnosis is established, trying to predict their biologic behavior is even more important. The Weiss system, considered to be predictive of the biologic behavior of conventional (nononcocytic) adrenocortical tumors, has been recently reviewed in the context of its possible application to the oncocytic tumor variant, along with the introduction of the size and weight parameter. Definitional criteria (mainly cells with eosinophilic and granular cytoplasm, high nuclear grade, diffuse architectural pattern) common to all types of oncocytic tumors are outlined, and proposed major criteria (high mitotic rate, atypical mitoses, venous invasion) and minor criteria (large size and huge weight, necrosis, capsular invasion, sinusoidal invasion) for distinguishing malignant tumors are discussed. As a starting point for this discussion, a case of uncertain malignant potential is presented. The authors’ proposed working rules for diagnostic categorization of such tumors are defined, with the presence of 1 major criterion indicating malignancy, 1 to 4 minor criteria indicating uncertain malignant potential (borderline), and the absence of all major and minor criteria indicative of benignancy.

Colour Doppler ultrasonography for detecting perineural invasion (PNI) and the value of PNI in predicting final pathological stage: a prospective study of men with clinically localized prostate cancer.

To assess the ability of colour Doppler transrectal ultrasonography (CD‐TRUS) to improve the accuracy of detecting perineural invasion (PNI, reported to be an independent predictor of extraprostatic extension) and in predicting the pathological stage of the cancer, comparing it with the results of grey‐scale TRUS‐guided biopsies.

Selected case from the Arkadi M. Rywlin International Pathology Slide Seminar: Sporadic lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a systemic, progressive, and fatal condition affecting almost exclusively women in their reproductive years. LAM most often occurs as a sporadic disease, but also occurs in women with tuberous sclerosis complex (TSC) (syndromic LAM). There are no pathologic differences between sporadic and syndromic LAM. Sporadic LAM is a rare disease with prevalence of approximately 1 to 2 cases per million women in the United States and among populations of white descent, and is even rarer among Asian and African individuals. Syndromic LAM affects 4% to 5% of women with TSC. Sporadic LAM is often found also in association with renal angiomyolipoma, the most common sign of TSC, but LAM associated with angiomyolipoma does not define TSC. Although LAM is not diagnostic for TSC either in isolation or in association with angiomyolipoma, still it is considered by some researchers as an incomplete expression (forme fruste) of TSC. LAM may involve the lungs and the axial lymphatics and lymph nodes of the thorax and retroperitoneum. In sporadic LAM, thoracic, intraabdominal, and cervical lymph nodes can be involved with or without lung involvement. The diagnosis of LAM is often delayed. A case of LAM in a young lady, which was complicated with pleural and peritoneal chylous effusions, is presented. The diagnosis was first made on a retroperitoneal lymph node biopsy. The patient had a prolonged prior history of respiratory problems owing to lung involvement, and eventually died 2 years after diagnosis. Focus on the clinicopathologic diagnosis of TSC is also made.

Tuberous Sclerosis Complex With Polycystic Kidney Disease of the Adult Type: the TSC2/ADPKD1 Contiguous Gene Syndrome

Although different diseases, tuberous sclerosis complex and autosomal dominant polycystic kidney disease have been seen in association, the molecular basis of this being the proximity of tuberous sclerosis complex 2 and polycystic kidney disease 1 genes on the same chromosome (16p13.3). Therefore, the classic autosomal dominant polycystic kidney disease renal phenotype may occur in the context of tuberous sclerosis complex disease as a result of large deletions involving both the polycystic kidney disease 1 and tuberous sclerosis complex 2 genes. This is known as the tuberous sclerosis complex 2/autosomal dominant polycystic kidney disease 1 contiguous gene syndrome. The criteria for this condition are fulfilled when renal lesions typical for classic autosomal dominant polycystic kidney disease phenotype are associated with tuberous sclerosis complex phenotype. We present a new case of the sporadic form of this genetic disorder. The diagnosis of tuberous sclerosis complex in this patient was established on the presence of major and minor features, and the diagnosis of ADPKD was based on the presence of numerous large roundish renal cysts lined by a nondescript tubular epithelium. Sporadic cases of autosomal dominant polycystic kidney disease and tuberous sclerosis complex do occur. Molecular analysis was not performed because the patients parents refused permission.

Rapidly Growing Mass in the Parotid Gland

An 18-year-old girl was referred to the Oral & Maxillofacial Surgery Department at the Barzilai Medical Center, Ashkelon, Israel, with a main complaint of a painless, rapidly growing, mass in the right parotid region of 3 months’ duration. Before this consultation she had been seen elsewhere, where an ultrasound of right facial region was performed, showing a cystic-like lesion in the right parotid area and enlarged lymph nodes in the posterior neck region. Her medical history was uneventful, and she was taking no medications. Facial examination showed 3 2-cm mass in the tail region of the right parotid gland (Fig 1). The mass was hard, mobile, and seemed to be located deep in the gland. There was no evidence of facial nerve weakness. Oral examination showed reduced salivary flow from the right Stenson’s duct. The oral mucosa was normal, and the teeth were in good condition. Blood studies showed an increased erythrocyte sedimentation rate (30 mm first hour and 60 mm second hour) and slightly increased neutrophils. Sialography of the right parotid gland showed normal gland architecture. Axial computerized tomography showed a 2.5 3-cm mass in the deep lobe of the right parotid gland (Fig 2).