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April 2001
Identifying metanephric stromal tumor: a novel pediatric renal neoplasm
Only a small percentage of pediatric renal neoplasms can be classified as stromal, however an accurate diagnosis of the specific type of stromal neoplasm is crucial, particularly to avoid the damaging effects of unnecessary chemotherapy. The authors described the clinical, histologic, and immunohistochemical findings of a unique pediatric stromal neoplasm designated as metanephric stromal tumor (MST). Twenty-four of 31 cases were identified on retrospective review of cases coded as congenital mesoblastic nephroma (21 cases) and clear cell sarcoma of the kidney (three cases). Some of the important features that distinguish MST include alternating cellularity imparting a nodular low power appearance; onion-skin cuffing around entrapped renal tubules; angiodysplasia of intratumoral arterioles characterized by epithelioid transformation of medial smooth muscle with a myxoid stromal change; and heterologous differentiation (cartilage/glial) and juxtaglomerular cell hyperplasia in entrapped glomeruli. Immunoreactivity for CD34 (12/13 cases) but not for desmin (0/12 cases) further help in characterizing MST and separating it from clear cell sarcoma of the kidney and congenital mesoblastic nephroma. The authors reported that MST forms a continuous morphologic spectrum with metanephric adenofibroma. Embryonal epithelial hyperplasia associated with native renal elements may be seen in MST, however, when it occurs unassociated with native renal elements, the authors would classify such tumors as metanephric adenofibroma. In three patients, the vascular alterations were prominent and associated with extrarenal vasculopathy and resultant morbidity. In none of the 22 cases with followup (range, 14 months to 13 years) was recurrence or metastasis noted. The authors cautioned that there is potential for MST to be associated with an adverse outcome and that they have observed Wilms tumor arising in association with lesions morphologically identical to MST.
Argani P, Beckwith JB. Metanephric stromal tumor: report of 31 cases of a distinctive pediatric renal neoplasm. Am J Surg Pathol. 2000;24:917-926.
Reprints: Dr. Pedram Argani, The Johns Hopkins Hospital, Pathology Building, Room 612, 600 N. Wolfe St., Baltimore, MD 21287; pargani@pds.path.jhu.edu
Detecting ETV6-NTRK3 chimeric RNA: application to pediatric renal stromal tumors
A novel chimeric fusion transcript resulting from t(12;15)(p13;q25) was recently identified in the cellular variant of congenital mesoblastic nephroma and infantile fibrosarcoma but not in the classic form of CMN, infantile fibromatosis, or adult-type fibrosarcoma. The authors reported the development of a RT-PCR assay to detect this fusion transcript in formalin-fixed, paraffin-embedded tissue and its application to renal stromal tumor cases, including the mixed variant of CMN. The fusion transcript was identified in 18 of 20 cases of the cellular variant of CMN and two problematic cases that could be mistaken on histology for rhabdoid tumor and clear cell sarcoma of the kidney. The transcript was not identified in the classic variant of CMN (0/4) and several pediatric renal tumors that were tested. None of five cases of the mixed type of CMN were positive for the fusion transcript. Variation in the fusion breakpoint is a potential limitation of this technique, however such variation has not been reported. The authors suggested that the absence of the fusion transcript in the mixed type of CMN in this study may imply that this type represents more than one genetic entity. The amount of the fusion transcript in these tumors, however, may be at the level that is below the threshold for detection by this technique. The study illustrates the utility of this technique in distinguishing the cellular variant of CMN from tumors that may mimic other morphologic types. This distinction is clinically significant in preventing unnecessary, potentially toxic chemotherapy.
Argani P, Fritsch M, Kadkol SS, et al. Detection of the ETV6-NTRK3 chimeric RNA of infantile fibrosarcoma/cellular congenital mesoblastic nephroma in paraffin-embedded tissue: application to challenging pediatric renal stromal tumors. Mod Pathol. 2000;13:29-36.
Reprints: Dr. Pedram Argani, The Johns Hopkins Hospital, Pathology Building, Room 612, 600 N. Wolfe St., Baltimore, MD 21287; pargani@pds.path.jhu.edu
Optimizing the pathologic examination of sentinel lymph nodes in patients with carcinoma of the breast
The proper method for the pathologic handling of sentinel lymph nodes is controversial, with members of the medical community debating protocols for gross and microscopic sectioning as well as the necessity for immunohistochemical staining. The authors of this study retrospectively examined 112 sentinel lymph nodes from 89 patients to develop a computer-based mathematic model to determine optimal gross and microscopic sampling techniques. Six commonly used sectioning strategies were compared with a more exhaustive strategy that entailed cutting the lymph node at 2-mL intervals and then making 10 histologic sections through the block. When a 500-µm metastasis was assumed, the detection rate for the six commonly used techniques ranged from 20 to 75 percent, with four of the techniques having a probability of detection of less than 30 percent. The detection rate for the commonly used methods was significantly lower for a metastasis of 200 µm and was generally poor by all methods for a metastasis of 50 µm. The cost of the 10-level method was significantly greater than for any of the other methods employed. As with all mathematical modeling exercises, certain assumptions were made, some of which might induce considerable error. The authors felt, however, that the error would apply to all scenarios and thus not significantly bias the comparison between different sampling strategies. Because sentinel lymph node findings may impact decisions regarding the need for formal axillary dissection and adjuvant chemotherapy, the authors concluded that an appropriate method for sentinel lymph node examination is needed. They also determined that pathologists and clinicians must agree on the minimal size of metastasis that will be sought histologically to select the most appropriate method for sentinel lymph node examination.
Farshid G, Pradhan M, et al. Computer simulations of lymph node metastasis for optimizing the pathologic examination of sentinel lymph nodes in patients with breast carcinoma. Cancer. 2000;89:2527-2537.
Reprints: Gelareh Farshid, Dept. of Pathology, University of Adelaide, and the Division of Tissue Pathology, Institute of Medical and Veterinary Science, Frome Rd., Adelaide, South Australia 5000
Imaging-histologic discordance at percutaneous breast biopsy
How to handle patients who have abnormal imaging studies but negative percutaneous breast biopsies is an uncommon but vexing problem for the radiologist, pathologist, and clinician. The authors reported on their experience with this problem, which is based on performing percutaneous imaging-guided breast biopsy on 1,785 consecutive lesions over a seven-year period. The lesions were approached under stereotactic (1,205) or sonographic (580) guidance using a variety of types and sizes of needles. The radiographic findings were prospectively categorized as probably benign, suspicious, or highly suggestive of malignancy. Discordant results included those where the histologic findings did not provide sufficient explanation for the appearance of the lesion by imaging techniques. Fifty-six discordant cases, accounting for 3.1 percent of all lesions, were identified. Features which tended to be associated with discordant results included biopsies performed during the early years of the institution’s experience with percutaneous breast biopsy (five percent during first two years, 2.7 percent thereafter), lesions highly suggestive of malignancy (4.8 versus 2.6 percent for lesions only suspicious for malignancy), and use of a device other than an 11-gauge vacuum-assisted probe for lesions defined by calcifications (1.7 versus 6.8 percent). Repeat biopsies performed in 45 discordant lesions showed an overall incidence of carcinoma of 24.4 percent, with lesions in the highly suggestive category having a subsequent carcinoma diagnosis of 43.8 percent, versus 13.7 percent for those in the suspicious category. The authors noted that careful coordination between the radiologist and pathologist is necessary when performing percutaneous imaging breast biopsies, and they concluded that, in discordant cases, excision of the lesion is indicated because of the high prevalence of carcinoma in such cases.
Liberman L, Drotman M, Morris EA, et al. Imaging-histologic discordance at percutaneous breast biopsy. An indicator of missed cancer. Cancer. 2000;89:2538-2546.
Reprints: Dr. Laura Liberman, Dept. of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021
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