Case Reports Passive Seeding in Metanephric Adenoma A Review of Pseudometastatic Lesions in Perinephric Lymph Nodes Gladell P. Paner, MD; Thomas M. Turk, MD; Joseph I. Clark, MD; Valerie Lindgren, PhD; Maria M. Picken, MD, PhD c Lymph node involvement derived from a discrete neo- longs to the spectrum of putatively nephrogenic rest-de- plastic process fundamentally implies tumor malignancy. rived tumors, which also include Wilms tumor (WT), However, rarely, inconsequential passive transport of be- metanephric adeno®broma (MAF), and metanephric stro- nign neoplastic cells to the lymph node can occur and may mal tumor.1±3 Although WT, or nephroblastoma, is thought cause confusion as to the nature of the neoplasm (ie, ma- to represent the malignant end of this spectrum, the other lignant vs benign). We describe a 10-cm right renal meta- metanephric neoplasms are generally regarded as benign, nephric adenoma incidentally discovered in a 30-year-old and thus far, only a few reports have suggested that a woman during cesarean section for a triplet pregnancy. small subset of these tumors can have atypical histologic Subsequent nephrectomy following an equivocal needle bi- features and behavior.3±6 Recently,acaseofMAina7- opsy diagnosis showed histologic features classic for meta- year-old child was reported with lymph node involvement nephric adenoma, including the lack of cytologic atypia that was interpreted as metastasis.7 and mitoses. Necrosis present in this lesion appeared to be Some cells indigenous to the lymph node could be mis- secondary to tumor physical disruption. The tumor cells taken for metastatic carcinoma, such as lymphoid follicles were positive for Wilms tumor 1 (WT1) antigen, pankera- or germinal centers protruding into sinuses, histiocytic tin, and CD57, focally positive for epithelial membrane an- granulomas, thick endothelial cells of postcapillary ve- tigen, and negative for cytokeratin 7, cytokeratin 34bE12, nules, and rarely, nodal megakaryocytes.8 Moreover, be- and CD56. Electron microscopy con®rmed the tumor's ep- nign cellular inclusions not native to the lymph node, such ithelial nature, and cytogenetics revealed a diploid 46XX as epithelial and hyaline or Tamm-Horsfall protein (THP)± karyotype. The tumor proliferation index with Ki-67 was associated epithelial inclusions, mesothelial inclusion cysts only 3% to 5% and the proliferating cell nuclear antigen (MICs), and rarely, mature squamous cells, have been de- index was 0%. A single, concurrently resected hilar lymph scribed in the perinephric lymph nodes of pediatric renal node contained scattered subcapsular, sinusoidal, and fo- patients from the National Wilms Tumor Study.8 The be- cally intralymphovascular psammoma bodies along with nign MICs, which are small cysts lined by a serous (muÈl- occasional adherent epithelial cells. These cells were high- lerian)±type epithelium, have long been recognized in the lighted by pankeratin but were nonreactive to WT1 anti- abdominal and pelvic lymph nodes of female patients gen, similar to the nonviable cells in the primary tumor. with gynecologic tumors.9 Clinical surveillance and follow-up showed no disease re- Herein, we describe an MA in a woman with multiple currence 4 years after nephrectomy. We postulate that the psammoma body±associated epithelial cells in the peri- lymph node inclusions found in this case represent passive nephric lymph node. Diagnosis of the primary kidney tu- transport of neoplastic cells to the lymph node following mor was supported by ancillary studies, including im- manipulation of the renal mass. We conclude that this phe- munohistochemical, cytogenetic, and electron microscopic nomenon is understudied and underrecognized and can studies. easily be mistaken for metastasis. (Arch Pathol Lab Med. 2005;129:1317±1321) REPORT OF A CASE A 30-year-old woman with a triplet pregnancy at 33 weeks of etanephric adenoma (MA) is an uncommon renal ep- gestation was admitted to Loyola University Medical Center fol- ithelial neoplasm of primitive appearance that be- lowing the premature rupture of membranes. She had an uncom- M plicated prenatal course and class D diabetes mellitus with a 23- year history of insulin use. There was no prior diagnosis of ma- lignancy, and her family history was unremarkable. She had no Accepted for publication May 31, 2005. history of blood polycythemia. Laboratory examination showed From the Departments of Pathology (Drs Paner, Lindgren, and Pick- mild leukocytosis with a white blood cell count of 11 900/mL en), Urology (Dr Turk), and Medicine (Dr Clark), Loyola University m Medical Center, Maywood, Ill. Dr Paner is now with the Department (reference range, 4000±10 000/ L); the rest of the complete blood of Pathology, Emory University, Atlanta, Ga. Dr Lindgren is now with cell count ®ndings were normal. The patient's other laboratory the Department of Pathology, University of Illinois, Chicago. ®ndings were as follows: glucose, 184 mg/dL (reference range, The authors have no relevant ®nancial interest in the products or 70±110 mg/dL) (10.21 mmol/L [reference range, 3.89±6.11 companies described in this article. mmol/L]); blood urea nitrogen, 19 mg/dL (reference range, 7± Reprints: Maria M. Picken, MD, PhD, Department of Pathology, Loy- 22 mg/dL) (6.78 mmol/L [reference range, 2.50±7.85]); and cre- ola University Medical Center, 2160 S First Ave, Bldg 110, Room 2242, atinine, 0.9 mg/dL (reference range, 0.7±1.5 mg/dL) (79.56 Maywood, IL 60153 (e-mail: [email protected]). mmol/L [reference range, 61.88±132.60 mmol/L]). A primary, low Arch Pathol Lab MedÐVol 129, October 2005 Passive Seeding in Metanephric AdenomaÐPaner et al 1317 Figure 1. Metanephric adenoma. A, The metanephric adenoma cells form papillary structures and tubuloacinar clusters in an eosinophilic acellular stroma (hematoxylin-eosin, original magni®cation 3200). B, There are wide areas of necrosis associated with granulation tissue formation (he- matoxylin-eosin, original magni®cation 340). C, An abortive glomerular structure composed of monomorphic metanephric adenoma cells with absent mitosis (hematoxylin-eosin, original magni®cation 3400). D, There is strong diffuse nuclear expression of Wilms tumor 1 (WT1) by the viable tumor cells, and the necrotic tumor ghost cells are showing no immunoreactivity (WT1, original magni®cations 3200 and 3400 [inset]). E, An area showing moderate membranous expression of CD57 by the tumor cells (CD57, original magni®cation 3400). F, Ultrastructurally, the tumor cells are closely apposed, with intercellular junctions, focally present basement membrane, and occasional microvilli projecting into the lumina. transverse cesarean section with the patient under epidural an- (CK7; prediluted, K72, Cell Marque, Hot Springs, Ark), esthesia was performed, and initially the postpartum recovery CK34bE12 (prediluted, Cell Marque), epithelial membrane anti- was uncomplicated. However, 4 days after the pregnancy delivery gen (EMA; prediluted, Mc5, Zymed, San Francisco, Calif), vi- procedure, the patient complained of dysuria followed by a spik- mentin (prediluted, 3B4, Ventana), WT1 (1:100, 6F-H2, Dako- ing fever. Urine culture test results were positive for Escherichia Cytomation, Carpinteria, Calif), CD56 or neural cell adhesion coli, and she was treated with an antibiotic regimen. Two days molecule (1:100, 123C3, Zymed), CD57 (prediluted, NK1, Cell later, she complained of right ¯ank pain, and subsequent ultra- Marque), estrogen receptor (prediluted, 6F11, Ventana), proges- sound revealed a large mass that measured approximately 10 cm terone receptor (prediluted, 1A6, Zymed), proliferating cell nu- in diameter located at the midlower pole of the right kidney. clear antigen (1:20, PC10, Dako), and Ki-67 (prediluted, 7B11, Scattered calci®cations within the renal mass with high attenua- Zymed). An electron microscopic study was performed as pre- tion were seen on computed tomography (CT). A CT-guided ®ne- viously described.6 For cytogenetic analysis, a fresh sample from needle aspiration (FNAB) biopsy specimen was suggestive of the tumor was disaggregated with collagenase (Sigma-Aldrich MA, but a low-grade papillary renal cell carcinoma (PRCC) could Co, St Louis, Mo), physically disrupted, and put into culture with not be ruled out. The results of subsequent radiologic surveys for Eagle minimal essential medium. Harvesting and staining fol- metastatic lesions were negative. Based on the equivocal FNAB lowed standard cytogenetic techniques. A total of 20 tumor cells diagnosis, a right radical nephrectomy was performed 6 weeks were examined. after the cesarean section and 1 week after the FNAB. During nephrectomy, an enlarged 2.5-cm hilar lymph node was noted, PATHOLOGIC FINDINGS which was also resected. The specimen submitted for pathologic examination was the entire right kidney, including the surround- The kidney had a bulging intraparenchymal mass lo- ing perinephric fat and Gerota fascia, attached proximal segment cated in the inferior renal pole. On sectioning, the mass of the ureter and hilar vessels, and the resected hilar lymph node. was well de®ned and fairly circumscribed, measured 10 The patient tolerated the surgery well and had an unremarkable cm in diameter, and involved both the renal cortex and postoperative recovery. Subsequently, she underwent interleukin medulla. The cut surface was solid brown with foci of 2 therapy, which was also well tolerated. The patient is alive with hemorrhages and necrosis. The renal pelvis was not in- no clinical evidence of