Nazeel Ahmad

Diagnostic digital cytopathology: Are we ready yet?

Background: The cytology literature relating to diagnostic accuracy using whole slide imaging is scarce. We studied the diagnostic concordance between glass and digital slides among diagnosticians with different profiles to assess the readiness of adopting digital cytology in routine practice. Materials and Methods: This cohort consisted of 22 de-identified previously screened and diagnosed cases, including non-gynecological and gynecological slides using standard preparations. Glass slides were digitalized using Aperio ScanScope XT (×20 and ×40). Cytopathologists with (3) and without (3) digital experience, cytotechnologists (4) and senior pathology residents (2) diagnosed the digital slides independently first and recorded the results. Glass slides were read and recorded separately 1-3 days later. Accuracy of diagnosis, time to diagnosis and diagnostician′s profile were analyzed. Results: Among 22 case pairs and four study groups, correct diagnosis (93% vs. 86%) was established using glass versus digital slides. Both methods more (>95%) accurately diagnosed positive cases than negatives. Cytopathologists with no digital experience were the most accurate in digital diagnosis, even the senior members. Cytotechnologists had the fastest diagnosis time (3 min/digital vs. 1.7 min/glass), but not the best accuracy. Digital time was 1.5 min longer than glass-slide time/per case for cytopathologists and cytotechnologists. Senior pathology residents were slower and less accurate with both methods. Cytopathologists with digital experience ranked 2 nd fastest in time, yet last in accuracy for digital slides. Conclusions: There was good overall diagnostic agreement between the digital whole-slide images and glass slides. Although glass slide diagnosis was more accurate and faster, the results of technologists and pathologists with no digital cytology experience suggest that solid diagnostic ability is a strong indicator for readiness of digital adoption.

Urothelial carcinoma in a child

OBJECTIVES Urothelial carcinoma of the bladder occurs rarely in the first 2 decades of life. We report a case of a 12 year-old child that presented with a Ta grade II/III urothelial carcinoma of the bladder. METHODS We describe its clinical presentation and diagnostic procedures as well as treatment and follow-up. Finally, we review the literature to analyze the etiology, treatment, and surveillance of urothelial carcinoma in the pediatric population. RESULTS Since 1950, there are less than 100 cases of urothelial carcinoma reported in patients less than 30 years, and even less in children and adolescents. Most of the small series describe these tumors as being characteristically superficial and low grade (I-ll). This child presented with silent macroscopic hematuria and an MRI revealed a solid and papillary mass measuring 2.7 cm. A cystoscopy and resection of the tumor confirmed the diagnosis. A re-resection at two months confirmed no residual tumor in the bladder. CONCLUSIONS There is no established criteria for the etiology, treatment, and surveillance of urothelial carcinoma in the pediatric population. Children with gross hematuria as the presenting complaint should undergo a complete evaluation to rule out the presence of urothelial carcinoma.

Multimodality management of a polyfunctional pancreatic endocrine carcinoma with markedly elevated serum vasoactive intestinal polypeptide and calcitonin levels.

We present an unusual case of a 52-year-old woman with severe, uncontrollable, refractory diarrhea attributable to pancreatic endocrine carcinoma (ECA) with markedly elevated serum vasoactive intestinal polypeptide (VIP) and calcitonin levels. After initial correction of fluid and electrolyte abnormalities, the patient was treated with high-dose octreotide. Shortly thereafter, due to the intractable nature of her diarrhea, she underwent cytoreductive hepatic surgery. The pancreatosplenectomy specimen showed a poorly differentiated ECA of the distal pancreas, immunoreactive for synaptophysin, CD56, and S100 protein, with morphologically similar hepatic and lymph node metastases. Postoperatively, her diarrhea improved, along with decline in serum VIP and calcitonin levels. Systemic chemotherapy with etoposide and cisplatin did not result in any radiographic and biochemical improvement. Having radiologically stable disease with depot-octreotide and short-acting octreotide (Sandostatin), she was subjected to peptide receptor radiotherapy with [177Lu-DOTA0,Tyr]octreotate (LuTate) that resulted in marked clinical and biochemical improvement, along with dramatic reduction in the number and size of hepatic metastases. In summary, this is a unique case of metastatic VIP- and calcitonin-secreting pancreatic ECA with dramatic sustained clinical, biochemical, and objective tumor response to peptide receptor radionuclide therapy.

Prostate adenocarcinoma: cellular and molecular abnormalities.

Adenocarcinoma of the prostate gland presents with a wide variety of clinical findings, ranging from asymptomatic, relatively latent tumors to highly aggressive, metastasizing cancers. Tumors predominantly arise from epithelial cells in the peripheral zone of the gland. Tumors that progress, if untreated, will extend into the prostatic capsule and seminal vesicles, and will ultimately metastasize to regional and distant sites such as lymph nodes and bone. Metastatic hormone-refractory disease is the most important cause of morbidity, treatment failure, and subsequent mortality from prostate cancer. The two main issues for clinicians and pathologists involved in prostate cancer are early detection of the cancer and identification of the prognostic factors that predict outcome in individual patients.1

Pathologic quiz case: a 57-year-old man with hypertension and hypokalemia.

A man with a past medical history significant for hypertension and non–insulin-dependent diabetes mellitus presented for evaluation of chronic hypokalemia. Initially, the low potassium levels were attributed to his antihypertensive medication. However, hypokalemia persisted despite discontinuation of all potassiumwasting diuretics and supplementation with 80 mEq of oral potassium daily. A metabolic workup showed a plasma potassium level of 2.7 mEq/L (reference range, 3.3–4.7 mEq/L) and a plasma aldosterone level of 47 ng/dL (reference range, 4–31 ng/dL) (1.30 nmol/L; reference range, 0.11–0.86 nmol/L). The plasma renin activity was decreased, with a plasma aldosterone–plasma renin activity ratio of 47. The sodium level was mildly elevated at 148 mEq/L (reference range, 137–145 mEq/L). The magnesium, chloride, and bicarbonate levels, pH, white blood cell count, and cortisol levels were all within the reference ranges. The patient was given spironolactone therapy. A radiologic workup with abdominal computed tomography and magnetic resonance imaging demonstrated a left renal mass with solid and cystic components that was 3.2 cm in greatest dimension; the workup also revealed enlargement and prominence of the left adrenal gland. The patient underwent left adrenalectomy and partial left nephrectomy. The 14-g left adrenal gland measured 4.8 3 3.0 3 2.0 cm and contained 4 golden yellow, wellcircumscribed nodules scattered throughout the cortex that ranged from 0.3 to 0.8 cm in greatest dimension. The remaining normal adrenal cortex was unremarkable. The nodules did not invade the adrenal capsule or adrenal medulla. Within the parenchyma of the left partial nephrectomy specimen was an oval, well-circumscribed, centrally cystic, variegated yellow-gray to tan nodule that was 3.2 cm in greatest dimension. Microscopically, the cells of the adrenal nodules ranged from large, pale, lipid-rich cells resembling the zona fasciculata to eosinophilic cells with a granular cytoplasm resembling the zona glomerulosa. There were areas of mild nuclear and cellular pleomorphism without anaplasia or necrosis. Focally, the cells of the nodules contained small eosinophilic intracytoplasmic inclusions with a laminated appearance surrounded by a clear halo (Figure 1). A Luxol fast blue stain of these inclusions was characteristic of the pathologic entity (Figure 2). The nodules were partially surrounded by a fibrous pseudocapsule. The re-