SP Web 7-2-09 Case 1: History: 40 year-old female with diarrhea following treatment of pneumonia. Your Diagnosis: a) Ulcerative colitis b) Crohn’s disease c) Collagenous colitis d) Pseudomembranous colitis Answer: D Description: The colectomy specimen demonstrates a mucosal necrosis pattern, including epithelial cell necrosis, fibrin in the lamina propria, and pseudomembranes formed by fibrin, mucus, degenerating neutrophils and degenerating epithelial cells. While this morphology may be seen in patients suffering with ischemia or E. coli 0157:H7 infection, the morphology is typical of antibiotic-associated pseudomembranous colitis caused by C. difficile. Differential Diagnosis: Ulcerative colitis and Crohn’s disease would demonstrate signs of a chronic colitis; i.e., crypt distortion, crypt atrophy, and metaplasia. Collagenous colitis does not demonstrate the marked activity and mucosal necrosis seen in pseudomembranous colitis. Severe C. difficile colitis may result in full thickness mucosal necrosis and toxic megacolon, requiring colectomy as was the case here. Case 2: History: 43 year-old female with a 7 cm adrenal mass Your Diagnosis: a) Granulocytic sarcoma b) Myelolipoma c) Diffuse Large B Cell lymphoma d) Adrenal cortical carcinoma Answer: B Description: Within the adrenal there is a highly cellular proliferation of normal hematopoetic elements associated with fat. One sees megakaryocytes, a spectrum of maturing granulocytes, and islands of erythroid precursors. These are the typical features of a myelolipoma. Differential Diagnosis: Granulocytic sarcoma would feature sheets of primitive granulocytic cell precursors. Diffuse large B-cell lymphoma would feature sheets of pleomorphic lymphocytes with irregular nuclear contours and prominent nucleoli. Adrenal cortical carcinoma would demonstrate more polygonal cells with eosinophilic cytoplasm, reminiscent of the cytology of the normal adrenal cortex. Adrenal cortical carcinoma demonstrates cytologic atypia, and characteristically shows vascular and capsular invasion. Myelolipomas which are fat-poor, like the current case, are often difficult to distinguish from other adrenal lesions by imaging. . Case 3: History: 21 year-old male with a bladder polyp Your Diagnosis: a) Polypoid cystitis b) Inflammatory myofibroblastic tumor c) Botryoid embryonal rhabdomyosarcoma d) Eosinophilic cystitis Answer: C Description: Much of this fragmented biopsy is histologically bland, and could pass for an inflammatory polyp in that the stroma is myxoid and the cells do not show cytologic atypia. However, in other areas of the biopsy there is condensation of primitive stromal cells beneath the epithelium, forming a so-called “cambium-layer.” These primitive cells have wisps of eosinophilic cytoplasm, and were immunoreactive for myogenin and desmin on immunostains. Differential Diagnosis: Polyp formations are often seen in patients with cystitis, particularly in association with a stent. Inflammatory myofibroblastic tumor (IMT) would not demonstrate immunoreactivity for Myogenin, and often labels for ALK. The cells of an IMT generally have more hypochromatic nuclei than those of a rhabdomyosarcoma. Eosinophilic cystitis may be seen in patients with allergic conditions; however, in most cases eosinophilic infiltration of the bladder is secondary to a prior biopsy. Eosinophilic cystitis would not show the spindle-cell proliferation seen in the current case. Botryoid embryonal rhabdomyosarcoma is associated with a favorable prognosis relative to other subtypes of rhabdomyosarcoma. Case 4: History: 74 year-old male with cirrhosis and liver mass Your Diagnosis: a) Hepatocellular carcinoma b) Hepatocellular adenoma c) Focal nodular hyperplasia d) Regnerative nodule Diagnosis: A Description: The background liver shows areas of steatosis, and foci of regenerative hepatocyte nodules surrounding by fibrosis. Cirrhosis was better developed in other parts of the liver. The neoplasm consists of thickened trabeculae of hepatocytes. The trabeculae are often over 5 cells in thickness, and the cells demonstrate a high nucleus to cytoplasm ratio, pleomorphism, and readily identifiable mitotic figures. The cytoplasm is eosinophilic and granular and resembles that of the non-neoplastic hepatocytes. These are the typical features of hepatocellular carcinoma. Differential Diagnosis: Hepatocellular adenoma is a diagnosis which should not be made in the presence of significant cytologic atypia and mitotic figures. It is typically seen in young females who are taking oral contraceptives. Focal nodular hyperplasia features bile duct proliferation in association with benign hepatocytes, and essentially resembles cirrhosis (hence the old terminology, focal cirrhosis). Regenerative nodules in cirrhosis may feature expansions of hepatocytes, but the trabeculae should be 2 cells thick or less, and significant cytologic atypia should not be present. Case 5: History: 63 year-old female with a lung mass. Your diagnosis: a) Bronchioloalveolar carcinoma b) Micropapillary carcinoma c) Atypical adenomatous hyperplasia d) Usual interstitial pneumonia Answer : B Description: An ill-defined nodule is present within the lung, and it demonstrates central elastosis. At the periphery, one sees atypical pneumocytes lining thickened alveolar septa. At high power, one sees tufts of atypical pneumocytes projecting into distorted alveolar spaces. These tufts demonstrate marked cytologic atypia, and lack fibrovascular cores. This is the typical architecture of a micropapillary carcinoma. Differential Diagnosis: Bronchioloalveolar carcinoma will feature atypical pneumocytes lining essentially intact, thin alveolar septa. The micropapillary projections seen in the current case should not be present. Atypical adenomatous hyperplasia would feature small (usually less than 5 mm) areas of atypical pneumocytes with minimal cytoplasm lining intact alveolar spaces. The advanced cytologic atypia seen in the current case would not be present. It is always important to consider usual interstitial pneumonitis before diagnosing a pulmonary adenocarcinoma. One may see cytologic atypia, often accentuated on frozen section, in areas of UIP with honeycomb change. In this case, the absence of cilia and the advanced cytologic atypia, along with the absence of other typical features of UIP (such as fibroblast foci, honeycomb change, or temporal heterogeneity of inflammatory changes), exclude this diagnosis. Micropapillary carcinomas may be seen in a variety of organs. Common sites include the breast, lung, bladder and salivary gland. This morphology is associated with high-stage in all sites. Reference: Adv Ant Pathol 2004; 11:297-303. Case 6: History: 77 year-old female with an endobronchial lung mass Your diagnosis: a) Carcinoid tumor b) Atypical carcinoid tumor c) Large cell neuroendocrine carcinoma d) Small cell carcinoma Answer: A Description: This is an endobronchial mass which protrudes into the lumen of the bronchus without overlying epithelium. The neoplastic cells grow in ribbon-like, trabecular pattern. While the lesion appears to be highly cellular at low power, at high power one can appreciate the uniform, “salt & pepper” chromatin of the neoplastic cells. Mitotic figures are extremely scant (less than 2 per 50 high power fields), and there is no necrosis. These are the typical features of a pulmonary carcinoid tumor. Differential Diagnosis: Atypical carcinoid tumor would feature either an increased mitotic rate or foci of necrosis. Large cell neuroendocrine carcinoma and small cell carcinomas are high-grade carcinomas, so they typically feature extensive necrosis and mitotic rates greater than 1 per high power field. Small cell carcinoma features fusiform cells with hyperchromatic nuclei that show nuclear molding, while large cell neuroendocrine carcinoma features polygonal cells with vesicular chromatin and prominent nucleoli.