Thyroid-like follicular carcinoma of the kidney (TLFCK) is a rare histological variant of renal cell carcinoma not currently included in the World Health Organization classification of renal tumors. Only 24 previous cases of TLFCK have been reported to date. We report a case of TLFCK in a 19-year-old woman with history of pediatric acute lymphoblastic leukemia. This patient is the youngest with TLFCK to be reported to date and the first with history of lymphoblastic leukemia. The development of TLFCK in a young patient with history of lymphoblastic leukemia is interesting and suggests that genes involved in leukemogenesis may also be important for TLFCK pathogenesis. Recognition of TLFCK is important to distinguish it from other conditions that show thyroid-like features, as a misdiagnosis can result in adverse patient care.
Thyroid-like follicular carcinoma of the kidney (TLFCK), also known as thyroid follicular carcinoma-like tumor of the kidney or thyroid follicular carcinoma-like renal tumor, is a rare and recently described subtype of renal cell carcinoma (RCC) not included in the 2004 World Health Organization (WHO) classification of renal tumors [
Clinicopathological features of thyroid-like follicular carcinoma of the kidney.
Case | Reference | Age (years)/gender | Clinical presentation | Location | Size (cm) | Previous malignancy | Follow-up |
---|---|---|---|---|---|---|---|
1 | Jung et al. [ |
32/F | Incidental | Right kidney, mid-pole + lower pole | 11.8 | nd | 6 months, ANED |
2 | Sterlacci et al. [ |
29/F | Incidental | Left kidney, mid-pole | 5.0 | nd | 60 months, ANEDa |
3 | He et al. [ |
22/F | Painless hematuria | Left kidney | 8.0 | nd | nd |
4 | Amin et al. [ |
53/F | Incidental | Right kidney, mid-pole | 2.1 | Primary osteosarcoma of rib, s/p chemotherapy | 54 months, ANED |
5 | Amin et al. [ |
29/F | Incidental | Right kidney, upper pole | 1.9 | nd | 84 months, ANED |
6 | Amin et al. [ |
45/M | Incidental | Right kidney, lower pole | 3.5 | nd | 17 months, ANED, then lost to follow-upb |
7 | Amin et al. [ |
83/M | Incidental | Left kidney, lower pole | 2.1 | Primary colonic adenocarcinoma, s/p chemotherapy | 48 months, ANED |
8 | Amin et al. [ |
35/M | Incidental | Right kidney, mid-pole | 3.0 | nd | 20 months, ANED |
9 | Amin et al. [ |
50/M | Incidental | Right kidney, mid-pole | 4.0 | nd | 7 months, ANED |
10 | Xu and Zang [ |
36/F | Hematuria | Left kidney, mid-pole + lower pole | 10.0 | nd | 12 months, ANED |
11 | Dhillon et al. [ |
34/F | Flank pain, gross hematuria | Right kidney, mid-pole | 6.2 | nd | 3 monthsc |
12 | Khoja et al. [ |
31/F | Flank pain, gross hematuria, weight loss | Left kidney, upper-mid-pole | 4.0 | nd | 21 months, ANED |
13 | Alessandrini et al. [ |
76/M | Gross hematuria | Left kidney, upper pole | 4.5 | Prostatic adenocarcinoma at age 71 y, s/p radical prostatectomy and adjuvant radiotherapy | 11 months, ANED |
14 | Alessandrini et al. [ |
41/F | Incidental | Right kidney, lower pole | 4.3 | Hodgkin lymphoma, s/p splenectomy and chemoradiotherapy | 4 months, ANED |
15 | Dhillon et al. [ |
34/M | Flank pain | Left kidney | 2.8 | nd | nd |
16 | Malde et al. [ |
29/F | Abdominal pain | Left kidney, lower pole | 6.5 | nd | 4 months, ANED |
17 | Wu et al. [ |
26/F | Incidental | Right kidney | 4.0 | nd | nd |
18 |
Wu et al. [ |
25/F | Hypertension | Right kidney, upper pole | 2.5 | nd | 18 months, ANED |
19 | Li et al. [ |
65/M | Hematuria, flank pain | Right kidney, mid-lower pole | 8.0 | nd | 15 months, ANED |
20 | Tang et al. [ |
66/M | Gross hematuria, flank pain | Right kidney | 16.0 | nd | 20 months, ANED |
21 | Berens et al. [ |
58/M | Incidental autopsy finding | Left kidney | 3.0 | Acute myeloid leukemia + prostatic adenocarcinoma | Diedd |
22 |
Volavšek et al. [ |
34/M | Abdominal pain | Left kidney, lower pole | 5.5 | nd | 6 months, ANED |
23 | Vicens et al. [ |
34/F | Gross hematuria, flank pain | Right kidney, interpolar | 6.2 | nd | ASDe |
24 | Lin et al. [ |
59/M | Incidental | Right kidney, mid-lower pole | 6.0 | nd | 1 month, ANED |
25 | Current case | 19/F | Abdominal pain | Right kidney, lower pole | 2.0 | Acute T-lymphoblastic leukemia at age 5 y, s/p chemotherapy | 21 months, ANED |
bRenal hilar lymph node metastasis at initial diagnosis.
cLung and retroperitoneal lymph node metastases at initial diagnosis.
dDied of complications of acute myeloid leukemia after chemotherapy 18 days after hospitalization.
eLung and lymph node metastases at initial diagnosis, on sunitinib malate with stable lung metastases and no evidence of local recurrence or new metastases.
F: female.
M: male.
ANED: alive with no evidence of disease.
ASD: alive with stable disease.
nd: not described.
We report a case of TLFCK arising in a 19-year-old woman with history of childhood T-cell acute lymphoblastic leukemia (T-ALL). This patient is the youngest with TLFCK to date and the first with history of lymphoblastic leukemia. Atypical features such as the presence of isolated tumor cells and renal capsular invasion with cyst formation were also identified. Isolated tumor cells in TLFCK have not been previously described, to the best of our knowledge. A recent study showed that the mixed-lineage leukemia/trithorax homolog (MLL) gene is overexpressed in TLFCK when compared to clear cell and chromophobe RCC [
A 19-year-old woman presented with right sided abdominal pain. Her past medical history was significant for T-ALL, diagnosed at 5 years of age. Flow cytometry and immunophenotyping on bone marrow showed the leukemic cells to be CD2−, CD7+, terminal deoxynucleotidyl transferase (Tdt)+, CD10+, and CD34+, consistent with T lymphoblasts. Her leukemia has remained in remission since treatment.
Abdominal computed tomography (CT) scan showed a 2.8 × 2.3 × 2.3 cm heterogeneous, hyperdense, and partially exophytic lesion in the right lower kidney (Figure
Imaging of TLFCK. (a) Coronal and (b) axial computed tomography with contrast showing a heterogeneous enhancing right renal mass.
The patient subsequently underwent a needle core biopsy of the right renal mass followed by a right partial nephrectomy without complication. At 21 months after partial nephrectomy, there was no evidence of tumor recurrence or metastatic disease.
The biopsy and partial nephrectomy specimens were routinely fixed in 10% buffered formalin, embedded in paraffin, and serially sectioned. Routine staining with hematoxylin and eosin was performed. Immunohistochemical staining was performed using the avidin-biotin-peroxidase complex method on a BenchMark ULTRA processor (Ventana Medical Systems, Tucson, AZ, USA). Primary antibodies used include those for pancytokeratin (AE1/AE3), cytokeratin 7 (CK7), epithelial membrane antigen (EMA), thyroid transcription factor-1 (TTF-1), thyroglobulin (TG), paired box gene 2 (PAX-2), PAX-8, CD10, CD56, S-100 protein, carcinoembryonic antigen (CEA), smooth muscle myosin heavy chain (SMMHC), Wilms tumor-1 (WT-1), vimentin, and Ki-67. Appropriate positive and negative controls were used for each antibody.
Needle core biopsy of the right renal mass demonstrated a focal atypical tubular epithelial cell proliferation (Figure
Histologic and immunophenotypic features of TLFCK on biopsy. (a) Low power view of biopsy showed an atypical area with microfollicles surrounded by chronic inflammatory reaction. (b) High power view demonstrated microfollicles with eosinophilic material filling tubular lumens. ((c) and (d)) Immunohistochemical staining of tumor cells showed reactivity for (c) CK7 and (d) EMA. ((e) and (f)) Tumor cells lacked immunoreactivity for (e) WT-1 and (f) CD56. Scale bars represent 100
The partial nephrectomy specimen measured 3.2 × 2.7 × 2.7 cm (Figure
Gross appearance of TLFCK. (a) Partial nephrectomy specimen with ruptured cyst (arrowhead) at the renal capsular surface. (b) Sectioning of specimen reveals a tan-brown partially cystic mass with focal hemorrhage, extending to the ruptured cyst at the capsular surface.
Microscopically, sections of the tumor revealed epithelial follicular structures varying in size and shape, surrounded by fibrotic stroma with a dense chronic inflammatory reaction (Figure
Histologic and immunophenotypic features of TLFCK. (a) Low power view of tumor demonstrated follicles of variably sized and shaped follicles filled with dense eosinophilic material. (b) Papillary-like structure extending into lumen of a macrofollicle. (c) High power view of microfollicular area. (d) Tumor extended to renal capsular surface (blue ink), with periodic-acid-Schiff (PAS) positive diastase resistant material identified within follicular lumens. (e) A focus of isolated tumor cells was located 1.8 mm from the main tumor. ((f)–(h)) Immunohistochemical staining of tumor cells showed reactivity for (f) CK7 and no reactivity for (g) TTF-1 or (h) thyroglobulin. Scale bars represent 100
The neoplastic epithelial cells were diffusely and strongly immunoreactive for CK7 (Figure
We report a case of TLFCK in a 19-year-old woman with history of treated pediatric T-ALL. TLFCK is a rare and recently described histologic variant of RCC that is not included in the current WHO classification of renal tumors [
Four cases of TLFCK were first described in abstract format by Amin et al. in 2004 [
The tumor in our case demonstrated features similar to previously reported TLFCK. Follicles of various sizes and shapes filled with eosinophilic material were found throughout the tumor, giving the tumor an appearance reminiscent of thyroid carcinoma. Amin et al. [
The immunohistochemical profile of the current tumor is comparable to previously reported TLFCK cases (AE1/AE3+, CK7+, PAX-2+, PAX-8+, vimentin+, EMA+, TTF-1−, TG−, CD56−, WT-1−, CD10−, and CEA−). A review of available TLFCK cases shows that most tumors are positive for AE1/AE3 (100%, 9/9 cases), CAM5.2 (100%, 3/3), PAX-8 (100%, 2/2), EMA (92.3%, 12/13), CK19 (85.7%, 6/7), CK7 (78.3%, 18/23), and vimentin (69.6%, 16/23). Variable expression in TLFCK can be seen for CK34
Twenty-four percent of TLFCK patients (6/25) had history of a previous malignancy (Table
Various genetic abnormalities have been identified in TLFCK [
The differential diagnosis of TLFCK includes renal metastases of thyroid carcinoma, other primary renal tumors with thyroid-like features, and thyroidization of renal tubules. Of primary concern is thyroid carcinoma metastatic to the kidney. As the management of metastatic thyroid carcinoma and TLFCK differ greatly, misdiagnosis can result in suboptimal patient management.
Renal metastases from primary thyroid carcinoma are relatively uncommon with fewer than 40 cases reported to date [
Thyroid-like features can occur in other primary renal tumors, as well as in extra-renal neoplasms. Specifically, thyroid-like features have been documented in upper tract urothelial carcinoma [
Similar to TLFCK, renal neuroendocrine (carcinoid) tumors are rare. Renal carcinoids have an increased incidence in horseshoe kidney [
Thyroidization of the renal tubules can occur in end stage renal disease, chronic pyelonephritis, or obstructive nephropathy. Unlike TLFCK which typically presents as a discreet mass, thyroidization of the renal tubules is often diffuse and involves bilateral kidneys.
In conclusion, TLFCK is a rare and recently described variant of renal carcinoma not included in the current WHO classification of renal tumors. Current consensus from the International Society of Urological Pathology (ISUP) is to not recommend TLFCK as a new WHO histological classification given the limited number of cases available for review [
The authors declare that they have no potential conflict of interests regarding the authorship and/or publication of this paper.
The authors thank Be Huynh, M.D., and Abbey Johnston, M.D., for their invaluable assistance in the preparation of this paper.