Case 4 -
Papillary Carcinoma of the Thyroid Metastatic to the Kidney
Cleveland , OH
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In 1995, the patient was a 63 year-old male with a history of papillary thyroid carcinoma S/P
thyroidectomy in 1980, and radical neck dissection in 1982. In 1982, he was diagnosed with
bilateral lung metastases; status post iodine-131 treatment in 1986. In 1991 and 1992, he received
chemotherapy and radiation therapy secondary to bilateral lung metastases, as well as hemoptysis.
On February 1995, the patient presented with a complaint of two months duration of heartburn,
regurgitation after eating, accompanied with nausea, vomiting, and easy satiety. He also reported a
weight loss of 10 lb. over a short period of time, and lack of appetite. At about the same time he
started having black stools, and reported feeling of dizziness. A duodenal mass was found on endoscopy.
An abdominal CT showed a partially cystic mass in the right abdomen originating either in the kidney or
in the adrenal gland.
Patient underwent angio-infarction and subsequent (5 months later) resection of a large right kidney
mass. During the course of resection, it was discovered that the tumor had eroded into the duodenum with
a pyeloduodenal fistula.
Case 4 - Slide 1
Grossly most of the kidney was involved by a neoplastic process partially solid, cystic and
extensively necrotic. The largest solid area of tumor was located in the lower pole and measured 3.0 cm
The two morphologic features that best characterized the lesion were the presence of papillae and the
nuclear changes. The papillae were formed by a central fibrovascular stalk covered by a neoplastic
epithelial lining. The better developed papillae were long with a complex arborizing pattern. Some of
the papillae were straight and slender, arranged in a parallel, regimented fashion; others were short and
stubby. The thickness and composition of the papillary stalk was variable. In most instances, the
papillary stalk was made up of loose connective tissue and variously sized thin-walled vessels. In some
cases, it was swollen by edema fluid or occupied by an abundant acellular hyaline material.
Occasionally, the stalk was infiltrated by lymphocytes or clusters of foamy or hemosiderin-laden
macrophages. Psammoma bodies and other calcific concretions were not present.
The nuclei of the cells lining the papillae had a round or slightly oval shape. The contour appeared
smooth on superficial examination, however closer inspection revealed subtle irregularities in the form
of indentationsand folds. The nuclear irregularities frequently manifested
in the form of grooves. Another peculiar feature of the nucleus was characterized by an empty appearance
of the nucleoplasm, which seems almost totally devoid of chromatin strands. These nuclei were similar to
the ones previously described as pale, optically clear, watery, empty, ground glass, and "Orhan Annie's
The tumor cells lining the papillary structures showed positivity for cytokeratin (CK) 19 (Figure 9),
CK7 (Figure 10), thyroid transcription factor-1 (TTF-1) (Figure 11), CD57 (Figure 12), thyroglobulin
(Figure 13), and negativity for CK20, AMACR, HMWCK, p63, CD10 and RCC Marker. These findings are
consistent with the diagnosis of metastatic papillary thyroid carcinoma.
Papillary carcinoma of the thyroid metastatic to the kidney.
Metastases of malignant tumor to the kidney are observed rather frequently at autopsy, but rarely
found clinically in living patients. Maeda et al. reviewed a total of 136 cases of metastatic renal
tumors including 38 cases from the Japanese literature . In autopsies, renal metastases outnumber
renal primary tumors by 4:1. Autopsies performed on cancer patients have found that 4.6-7.6% of patients
have metastases in the kidney, with frequencies of bilaterality and multiplicity being as high as 71-81%
. By contrast, primary renal cell carcinomas are rarely bilateral.
Even if, theoretically, all solid tumors may give rise to renal metastasis, secondary lesions to the
kidney occur more commonly in patients with lung tumors, breast cancer, melanoma, gastric carcinoma and
Reports in the literature suggest rates of non-lymphoma renal metastases of 1.5-1.8% of
the general population
Metastatic renal tumors present a worse prognosis than primary renal cancer. This seems to be because
the former progresses rapidly after its discovery. Renal metastasis should be suspected whenever there
is a known primary. Imaging features are rarely pathognomonic. In fact, many renal masses are small and
asymptomatic as the widespread use of CT and ultrasound has led to increased incidental detection.
CT is the most sensitive modality for detecting renal metastases. It can be used to evaluate the
extent of disease as well as other sites of involvement. Even so, small, solitary metastases can be
indistinguishable from small primary malignancies. Metastases are usually multiple, bilateral, and iso-
to hypodense (10-40 HU) on an unenhanced scan. They typically demonstrate limited enhancement after
contrast (5-15 HU), except in the case of highly vascular tumors (such as melanoma).
Papillary carcinoma of the thyroid is more common in women, with a ratio F:M ranging between 2:1 and
3:1. The mean age at the time of diagnosis ranges from 31 to 49 years. A total of 4-20% of patients
with papillary carcinoma develops distant metastasis during the course of their disease. Common sites of
distant metastases of differentiated thyroid cancer upon presentation include cervical lymph nodes, lung,
and bone; less common sites of metastases are the brain, liver, and skin.
Metastasis to the kidney caused by thyroid and follicular cancers is found in 2.8-3.8% and 6-20% of
cases, respectively . However, detection of thyroid carcinoma with clinically apparent kidney
metastases is rare, with 20 cases reported in the literature
Clinical and pathological features
were only accessible in a subset of cases (Table 1). The most common presenting symptom or sign was
hematuria, 7 to 37 years after having being treated for thyroid cancer
Of the 20
cases of renal metastases associated with well-differentiated thyroid carcinoma, 11 were from papillary
carcinoma (most of which were follicular-variant papillary carcinomas), and 8 were from follicular
carcinoma. Metastatic tumor involved the right kidney in 6 cases, and the left kidney in 8. In 4 cases
there was bilateral involvement. One patient presented with an abdominal mass 3 years following
resection of a follicular carcinoma of the thyroid . In 3 patients the disease was discovered
incidentally during retrograde pyelography ,
and autopsy .
In the vast majority of the cases, the patients had known thyroid neoplasms at the time the renal
metastases were identified. Rarely, metastases to the kidney preceded the knowledge of the primary
thyroid neoplasm and were treated surgically as primary renal tumors.
Ruggiero et al.  reported a case of papillary thyroid carcinoma that presented with abdominal
pain in a 25-year-old woman with no previous history of thyroid disease. The patient underwent radical
nephrectomy for a right renal mass, which was diagnosed as papillary thyroid carcinoma-follicular
variant. During subsequent evaluation, metastatic disease was also identified in the patient's lungs.
Liou MJ et al.  reported a case of
papillary thyroid microcarcinoma with renal metastasis in a patient with widely disseminated disease,
including renal, pulmonary and pelvic bone metastases.
The management of patients with distant metastatic well-differentiated thyroid cancer includes
surgical resection of the primary tumor, radiotherapy, and ablation treatment with 131I.
Thyroid cancer metastatic to the kidney is rare clinically, but can be amenable to treatment with good
long term results . As many as 75% of patients with distant metastases caused by well-differentiated
thyroid cancer die within 5 years of diagnosis . Nevertheless, in patients with solitary late
distant metastasis of thyroid cancer, complete surgical resection may be proposed, in order to offer a
better chance of prolonged survival .
In conclusion, thyroid carcinoma should be considered in the differential diagnosis of a renal mass,
particularly in patients with a high serum thyroglobulin level, even if the renal mass is solitary and
unilateral, or no history of thyroid cancer is involved.
|Reference (#) ||sex/age ||tumor type ||presentation ||years after detection ||site|
|J Urol 1968  ||F/44 ||follicular ||abdominal mass ||3 ||bilateral, multiple nodules|
|Cancer 1979  ||F/49 ||follicular ||incidental finding (IVU} ||18 ||bilateral|
|J Urol 1982  ||F/66 ||follicular ||gross hematuria ||37 ||left kidney|
|Minerva Urol Nefrol 1991  ||F/- ||follicular ||neck nodule ||23 ||right kidney|
|J La State Med Soc 1992  ||M/53 ||papillary ||hematuria ||7 ||right kidney|
|Surg Today 1994  ||F/72 ||PTC-FV || - ||3 ||bilateral, multiple nodules|
|AJR Am J Roentgenol 1995  ||F/47 ||follicular ||hematuria ||7 ||right kidney|
|Am Surg 1995  ||M/75 ||PTC-FV ||gross hematuria ||no previous history ||left kidney|
|Nephron 1996  ||F/91 ||follicular ||incidental autopsy finding ||- ||left kidney|
|Clin Nucl Med 1999  ||F/65 ||follicular ||neck and sternal mass ||- ||left kidney|
|Nuklearmedizin 2000  || ||PTC-FV || || ||bilateral|
|Ann Urol (Paris)
1999  ||M/56 ||papillary ||low back pain ||3 ||left kidney|
|Thyroid 2001  ||F/61 ||PTC-FV ||upper back mass || - ||left kidney|
|Thyroid 2001  ||F/53 ||PTC-FV ||back pain || - ||right kidney|
|Anticancer Res 2003  || ||follicular || ||10 |
|Acta Otolaryngol 2005  ||F/50 ||PTC-FV ||low back pain ||no previous history ||right kidney|
|Int J Urol 2002  ||M/37 ||papillary ||incidental finding (US} || ||left kidney|
|An Med Interna 2002  || || || || ||left kidney|
|Am J Otolaryngol 2005  ||F/25 ||PTC-FV ||abdominal/flank pain ||no previous history ||right kidney|
|Endocr Pathol 1999  || ||PTC-FV ||hematuria and flank pain || |
|Present case ||M/63 ||papillary ||nausea, vomiting, easy satiety ||15 ||right kidney|
PTC-FV = papillary thyroid carcinoma - follicular variant.
The main differential diagnosis is withprimary Papillary Renal Cell Carcinoma (PRCC). PRCC comprises approximately 10% of renal
cell carcinomas. The reported mean age at presentation and sex ratio (M:F) ranges from 52-66 years and
1.8:1 to 3.8:1, respectively. PRCC frequently contains areas of hemorrhage, necrosis and cystis
degeneration. A pseudocapsule may be identified. Bilateral and multifocal tumors are more common in
PRCC than in others renal malignancies.
PRCC is characterized by malignant epithelial cells forming varying proportions of papillae and
tubules. The papillae contain a delicate fibrovascular core and aggregates of foamy macrophages and
cholesterol crystals may be present. Calcified concretions are common in papillary cores and adjacent
desmoplastic stroma. PRCCs typically express CK7, CK8, CK18, CK19, CAM 5.2, RCC CD10, and AMACR.
Micropapillary Urothelial Carcinoma of the upper urinary tract.
Micropapillary carcinoma is a rare variant of urothelial carcinoma, first described by Amin et al. in
1994 . The tumor resembles papillary serous carcinoma of the ovary. There is a male predominance
(M:F = 3.2:1) and the patient's age ranges from 5th to the 9th decade with a mean
age of 68 years. Almost all the reported cases occur in the urinary bladder, but it may also involve the
renal pelvis and the ureter . Histologically, two different patterns have been described in the
urinary tract: the invasive and the noninvasive. The noninvasive pattern of tumor consists of slender,
delicate fine papillary and filiform processes, with central fibrovascular cores. The papillae are lined
by cells with high nuclear grade showing either scant or abundant eosinophilic cytoplasm. Psammoma
bodies are infrequent. Micropapillary carcinomas are immunoreactive for CK7, EMA, CK20, Leu M1, and CEA.
Recognition of this growth pattern is important because of its aggressive behavior and to avoid
misdiagnosis with PRCC and with metastasis of papillary carcinoma from other organs.
Metastasis of papillary carcinoma to the kidney from other organs (i.e.
lung, and breast) should also be considered in the differential diagnosis.
The diagnosis of primary versus metastatic renal cell carcinoma (RCC) can sometimes be difficult,
because of the wide variety of histologic appearances and clinical presentations that RCC can assume.
The overlapping profile between PRCC and metastatic papillary thyroid carcinoma highlights the importance
of clinicopathologic correlation, and demonstrates the importance of using a panel of antibodies in
differentiating these tumors through immunohistochemistry.
Immunohistochemical Comparison of Papillary Thyroid Carcinoma (CA) from Papillary
Renal Cell Carcinoma.
Take Home Points
Primary renal cell carcinomas (RCC) are rarely bilateral; by contrast, metastatic tumors to the kidney are frequently (71-81%) bilateral and multiple.
| ||TTF-1 ||thyroglobulin ||CK17 ||CD57 ||AMACR ||CD117 ||RCC Ma ||CD15 ||CK7 ||EMA|
|Papillary Thyroid CA ||+ ||+ ||+ ||+ ||-/+||+ ||- ||-/+ ||+ ||+|
|Papillary RCC ||- ||- ||- ||- ||+ ||+/- ||+ ||+ ||+ ||+|
Renal metastasis should be suspected whenever there is a known primary.
Secondary lesions to the kidney occur more commonly in patients with lung tumors, breast cancer, melanoma, gastric carcinoma and lymphoma.
The overlapping IHC profile between some primary RCC and metastatic tumors to the kidney highlights the importance of clinicopathologic correlation, and demonstrates the importance of using a panel of antibodies in differentiating these tumors through immunohistochemistry.
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