Case of the Month: Genitourinary Pathology
A three-year-old male was brought to his pediatrician for persistent abdominal pain and distension; the boy was found to have a palpable abdominal mass on his right side. Following concerning findings on an initial ultrasound, the patient was found to have bilateral renal masses via computerized axial tomography, with the largest lesion involving the right kidney and measuring up to 11 cm. Given the bilateral nature of his disease, the patient was started on combination chemotherapy and an initial significant decrease in tumor size was noted. Unfortunately, repeat imaging performed several weeks further into treatment demonstrated new interval progression of the right kidney mass. Given these findings, the patient underwent a right-total nephrectomy.
Gross examination of the nephrectomy specimen demonstrated a 9.5 cm mass situated in the upper pole of the kidney, with apparent extension into the surrounding Gerota’s fascia. The tumor contained large areas of necrosis and hemorrhage with the intact portions of the lesion appearing pink-tan and fleshy. No other discrete macroscopic lesions were identified within the kidney.
Histologically, a majority of the tumor was composed of loosely cohesive sheets of small, round cells, with scant cytoplasm and overlapping nuclei (Figures 1 and 2).
Figure 1: Tumor in relation to surrounding kidney
Occasional foci of rosette-like structures were also appreciated, as well as scattered areas of tumor demonstrating rhabdomyoblastic-like features. Further examination of the lesion revealed significant areas of tumor exhibiting profound nuclear pleomorphism with hyperchromasia and atypical mitotic figures (Figure 3).
Figure 3: Foci of significant atypia and hyperchromasia
Immunohistochemical studies for P53 preferentially highlighted these areas of the lesion while the remaining portions of the tumor were non-reactive (Figure 4).
Figure 4: Immunohistochemical study for P53
(Hover the cursor over the link above to read the diagnosis for this case.)
While Wilms tumors (nephroblastomas) are uncommon, affecting approximately one in 8,000 children, they are the most common malignant tumor of the kidney in this population. Presenting often as an abdominal mass palpated by a parent, these tumors can also be associated with abdominal pain—as this patient experienced—or, rarely, with hypertension secondary to hyperreninism. With a combination of modern surgical intervention and chemotherapy, which often includes such agents as vincristine, dactinomycin and doxorubicin, it’s fortunate that most nephroblastomas have an excellent prognosis with an overall survival of more than 90 percent.
One significant unfavorable factor in nephroblastomas is the presence of diffuse anaplasia. While classic nephroblastomas are composed of a combination of blastemal, epithelial and stromal elements, with only mild cytologic atypia, foci of anaplasia demonstrate nuclear hyperchromasia, enlargement and multipolar mitotic figures. This finding, appreciated in about five percent of nephroblastomas, is typically defined as focal or diffuse. In this particular case, multiple foci of anaplasia were appreciated within the tumor with the surrounding lesion, demonstrating severe nuclear unrest. This latter finding, which is defined as pleomorphism falling short of anaplasia criteria, would qualify this patient’s tumor as having diffuse anaplasia. The presence of diffuse anaplasia has been related to TP53 mutations, a finding that can often be demonstrated using immunohistochemistry. Resistance to the standard chemotherapeutic regimen is the hallmark of nephroblastomas with diffuse anaplasia and is exemplified by the radiographic progression of the tumor in this case.
Approximately 10 percent of nephroblastomas are associated with an underlying syndromic condition. Interestingly, the histologic features of a particular tumor and findings within the surrounding kidney parenchyma can often provide a clue to which dysmorphic syndrome a patient may have. While stromal-predominant nephroblastomas are more commonly associated with WAGR or Denys-Drash syndromes, blastemal-predominant lesions are more common in Beckwith-Wiedemann syndrome. In this particular case, the patient also had multifocal perilobar nephrogenic rests within the surrounding kidney. This finding, in combination with the bilateral nature of his blastemal predominate tumors, raises the possibility of an underlying overgrowth syndrome, such as Beckwith-Wiedemann syndrome.
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