Cytodiagnosis of cutaneous metastasis from renal cell carcinoma: A case report with review of literature.

Cytodiagnosis of cutaneous metastasis of renal cell carcinoma (RCC) in the absence of history of primary tumor is difficult as it can be confused with other clear cell tumors. We report here a case of cytodiagnosis of cutaneous metastasis of RCC in a patient who had nephrectomy done 9 years back at some other centre, but did not have any records with him. Clinicians should be aware of the possibility of primary internal organ malignancy in patients presenting with cutaneous lesions and therefore conduct a careful examination and get necessary investigations. Prompt diagnosis and treatment will have its bearing on the eventual outcome.

Introduction

Renal cell carcinoma (RCC) accounts for 3% of all adult malignancies.[1] RCC has been well described for its frequency to metastasise, occurring in approximately one-third of patients at the time of diagnosis,[2] and in many cases during the course of the disease, affecting the lung, liver, lymph nodes and bone, with skin metastases being relatively quite rare.[3] We are presenting here a case of patient who was diagnosed of having cutaneous metastasis in the absence of primary diagnosis. A past history of nephrectomy done 9 years back could be elicited on exploration of past records. Though there are several reports of cutaneous metastasis from RCC diagnosed on histology, there are a very few reports on cytodiagnosis of cutaneous metastasis from RCC in the absence of primary diagnosis.[3] These metastatic deposits should be differentiated with primary skin tumors with similar cytomorphology.

Case Report

Clinical findings

A 62-year-old male presented with complaint of gradually increasing, painless, soft tissue swellings in right arm and lower back for 2 months. On examination, the swellings had soft to firm consistency and size of about 5×5 cm. Another swelling was noted on anterior chest wall adjacent to manubrium sternii on left side for last 1 month. No other significant past history was given at this point. Radiological investigations also did not give any evidence of non-neoplastic or neoplastic lesion. Fine needle aspiration from all the three swellings was done.

Cytological findings

On examining the smears from right arm and lower back swellings, normal looking adipocytes in a lipid rich background were seen. A diagnosis of lipoma was made. Smears from chest wall swelling were stained by May-Grόnwald-Giemsa (MGG) and Papanicolaou (Pap) stains. Smears were moderately cellular and showed variable number of large single cells and clusters of poorly cohesive cells tending to form acini at places [Figure 1]. Cells showed low nucleocytoplasmic (N/C) ratio, abundant pale cytoplasm with vacuoles and relatively indistinct cell borders. In some cells, nuclei were totally or partially stripped of cytoplasm, and some had large nucleoli and bland chromatin. In a few cells, intranuclear cytoplasmic inclusions were noted. Background was pale, foamy and vacuolated [Figure 2]. Based on smear examination, a diagnosis of “clear cell malignant tumor, possibly metastatic RCC” was made.

Figure 1

Cells with low N/C ratio and indistinct cell borders, tending to form acini at places, pale foamy background (MGG, ×50)

Figure 2

Variable number of single cells, clusters of poorly cohesive large cells, low N/C ratio, bland chromatin, abundant pale cytoplasm with vacuoles, relatively indistinct cell borders, large nucleoli, intranuclear cytoplasmic inclusions and vacuolated background (MGG, ×400)

Initially, the patient did not give any significant past history, but on further questioning, he revealed a history of kidney mass that was operated 9 years back at some other centre. Histopathology revealed it to be clear cell renal cell carcinoma. Biopsy of the chest swelling was advised for further confirmation, which showed metastatic RCC [Figure 3].

Figure 3

Biopsy of the chest swelling showing metastatic RCC (H and E, ×100)

Discussion

One large study of 6577 autopsies found 54 cases of unrecognised RCC and documented that the skin was the seventh most common site of metastasis.[4] However, usual sites of metastases from RCC are lung, lymph nodes and bones.[5] Three to 11% of renal carcinomas metastasise to skin.[6] RCC is the primary tumor in approximately 6% of skin metastasis.[78] Thus, it is not an uncommon site and therefore should be kept in mind while evaluating a patient with cutaneous lesion. Interestingly, spontaneous regression of skin metastases is reported.[9]

A Japanese literature review reported 75 cases of RCC associated with skin metastasis. The commonest site of metastasis was the trunk (40%), followed by the scalp (25%). Only 8% had metastases to the face. 24% had cutaneous metastases at the time of diagnosis.[3]

A large Indian study reviewing a total of 306 patients with RCC, seen over a 12-year period, found only 10 cases (3.3%) with skin metastases. Of these, half of the patients presented with skin metastases during follow-up after nephrectomy. Mean survival after detection of cutaneous metastasis was 7 months. Ahmad et al.[10] reported a similar case for its unusual presentation of RCC, occurring in a 65-year-old male presenting primarily as cutaneous metastasis to the chest, in the form of a skin nodule, even before the development of any urological presentation.

In another unusual case, a 39-year-old man, who had undergone left nephrectomy for RCC of clear cell type, was noted to have a solitary nodular shadow in the right lung on chest radiograph. Percutaneous needle biopsy of the lung was performed via the right anterior chest wall and the histological findings showed metastasis from renal carcinoma. Six months later, the patient presented with a cutaneous nodule at the site of puncture of the lung needle biopsy. Histological examination of a biopsy of the skin tumor revealed features of metastatic RCC of clear cell type.[11]

Due to the presence of predominant clear cells in this cutaneous mass, various cutaneous tumors with clear cell morphology were considered in the differential diagnosis and can be ruled out on the basis of their morphological features or special stains/immunohistochemisty (IHC). Clear cell sarcoma (CCS) is an anaplastic tumor consisting of cells derived from melanoblasts not forming melanin in the skin. These are positive for S-100, MART-1 and HMB-45 and are negative with keratin.[12] This clear cell variant of squamous cell carcinoma (SCC) may be easily mistaken histologically for a sebaceous neoplasm. Distinguishing features, however, include evidence of squamous differentiation and a negative fat stain using Oil Red O.[13] Other tumors which can be considered in the differential, in tumors with clear cells are as follows. Clear cell acanthoma do not show cellular atypia, and as they have abundant glycogen, staining with PAS or PAS with diastase can help us to distinguish them. Clear cell syringoma also do not show cellular atypia; IHC is helpful as they show positivity for CK 10 (intermediate cells), 6, 19 (luminal cells), CEA (peripheral cells). Clear cell porocarcinoma has large clear cells with polyhedral round to oval nuclei, abundant clear cytoplasm and distinct cell borders; intracytoplasmic lamina formation is present and cytoplasmic vacuoles are absent. Clear cells of RCC have abundant fragile, finely vacuolated cytoplasm, lacy/web like appearance due to irregular size vacuoles; cell borders are usually indistinct. These cells have low N/C ratio, round nuclei with variable anisokaryosis, nuclear chromatin is bland in low grade tumors, whereas macronucleoli can be seen in intermediate to high grade tumors.

To conclude, patients presenting with RCC, even with a low-stage disease, may develop cutaneous secondaries; therefore, its possibility should be borne in mind while evaluating a case of RCC. As it took 9 years for the metastasis to rear its ugly head in this case, a prolonged and thorough follow-up is mandatory.

Conversely, cutaneous metastasis is an uncommon manifestation of visceral malignancy, and in extremely rare cases, it may be the presenting sign of underlying malignancy.[14] Therefore, while evaluating a case of skin nodule showing malignant clear cells, RCC and along with other discussed differential diagnoses, should be considered.