Guided fine needle aspiration cytology of retroperitoneal masses - Our experience.

BACKGROUND: Early pathological classification of retroperitoneal masses is important for pin-point diagnosis and timely management. AIMS: This study was done to evaluate the usefulness and drawbacks of guided fine needle aspiration cytology (FNAC) of retroperitoneal masses covering a period of two years with an intention to distinguish between neoplastic and non-neoplastic lesions and to correlate with histologic findings.
MATERIALS AND METHODS: FNAC was done under radiological guidance in all cases using long needle fitted with disposable syringe. Appropriate staining was done and cytology was correlated with histology which was taken as the gold standard for comparison.
RESULTS: Fifty-one patients who presented with retroperitoneal masses were studied. Forty-four lesions were malignant cytologically and 7 were inflammatory (tuberculous). According to radiological and cytologic findings, we classified our cases into four groups: renal tumors, retroperitoneal lymphadenopathy, germ cell tumors, soft tissue tumors. Except for cases of non-Hodgkin lymphoma (NHL) and metastatic lesions, we had sensitivity and specificity of 100%. In NHL the sensitivity and specificity were both 50%. In cases of metastatic adenocarcinoma, the sensitivity and specificity were 84.6% and 81.8%, respectively.
CONCLUSIONS: Ignoring the pitfalls, guided FNAC is still an inexpensive and reliable method of early diagnosis of retroperitoneal lesions.

Introduction

The retroperitoneal space is a potential space extending from the lumbar till the pelvic region and contains important structures like adrenal glands, kidneys and ureters; pancreas; aorta and its branches; inferior vena cava and its tributaries; lymph nodes; and meshwork of loose connective tissue along with fat.[1]

The lesions in retroperitoneal space may present with clinical features like vague pain in the lumbar region, abdominal lump and deep vein thrombosis of lower limbs. For early pathological diagnosis, intervention is needed, which may be biopsy or guided fine needle aspiration cytology (FNAC).

Radiological guidance is practically always needed to ensure a representative sample, to avoid areas of necrosis and hemorrhage and to show the relation to major vessels and other structures.[2] FNAC is definitely advantageous as it is an easy-to-perform, cost-effective, and time-saving procedure with lesser complications than biopsy. Our aim was to establish the effectiveness of guided FNAC for diagnosis of retroperitoneal masses and to discuss the pitfalls, with possible alternatives.

Materials and Methods

This study was a collaborative effort of the Departments of Pathology, Radiodiagnosis and Gynaecology of a tertiary care government hospital covering a period of 2 years (January 2007 to December 2008). An initial approval was obtained from the ethical committee of the hospital which conforms to the norms of the Helsinki Declaration on human experimentation (institutional or regional).

Ultrasound (USG)-guided and/ or computerized tomography (CT) - guided FNAC was done for all retroperitoneal lesions using lumbar-puncture needle fitted to 20-mL disposable syringe. Cytologic stains used were May-Grünwald-Giemsa (MGG), hematoxylin and eosin (H and E) and Papanicolaou (PAP) stain. Ziehl-Neelsen (Z-N) stain was done whenever cheesy material or pus was aspirated to exclude tuberculosis. Cyto-diagnoses of all cases excepting those of tuberculous origin were correlated with diagnosis by histopathology, which was considered to be the gold standard.

Results

A total of 51 patients with retroperitoneal masses were aspirated under USG and/or CT guidance during the two-year study period. Most of the patients in our study presented with abdominal lump and/or dull aching pain in loin or abdomen. A few patients presented with unilateral leg edema, fever and weight loss. Twenty-six (50.98%) patients were male and 25 (49.02%) patients were female [Table 1].

Table 1

Age-sex distribution of cases

Out of 51 patients, 21 were aspirated under USG guidance; and the rest, under CT guidance. In all cases, yield was satisfactory for reporting. Renal cortical cysts were excluded from this study. The renal masses having solid or solid-cystic areas were aspirated. Nine out of 51 patients had renal masses, out of which 5 were diagnosed as renal cell carcinoma and four as Wilms’ tumor [Table 2]. The youngest patient was a 1-year-old male having Wilms’ tumor [Figure 1a], and the oldest was a 68-year -old female having renal cell carcinoma [Figure 1b]. In all the masses of renal origin, the cytological diagnosis correlated with diagnosis by histopathology.

Table 2

Distribution of different retroperitoneal SOLs diagnosed by guided FNAC

Figure 1

(a) Wilms’ tumor- biphasic tumor, cohesive tubular structure and undifferentiated mesenchymal cells (H and E, ×400); b) Renal cell carcinoma - poorly cohesive cells with abundant vacuolated cytoplasm and prominent nucleoli (MGG, ×400)

In our study, most of the retroperitoneal tumors were extra-renal, and lymphadenopathy was the commonest among them. Out of the 20 cases of lymphadenopathy, 2 were diagnosed as non-Hodgkin lymphoma (NHL); 7-inflammatory; and 11, as metastatic. All the inflammatory lesions were tuberculous with characteristic feature of epithelioid cell granuloma in caseous necrotic background and presence of acid-fast bacilli (AFB) in Z-N stained smears; hence histology was not required in these cases. Aspirates from two cases of lymph node masses had monomorphous population of lymphoid cells and were diagnosed as NHL, which were later histologically and immunohistochemically confirmed to be B-cell NHL. Nine out of the 11 metastatic lymph node masses had histologically proven metastatic adenocarcinoma. Two cases were histologically consistent with diffuse large B-cell lymphoma. So the cytologic diagnosis did not corroborate with the histologic diagnosis in two cases of lymph node masses.

We encountered eight cases of germ cell tumors, of which two were pure seminoma [Figure 2a] and the remaining two were yolk sac tumor [Figure 2b] diagnosed both on cytology and histology. Rest of the four cases were diagnosed as mixed germ cell tumor on histology; whereas on aspiration, two cases had the appearance of dysgerminoma; one, of yolk sac tumor; and another,of small blue round cell tumor [Table 3]. The youngest patient had yolk sac tumor, and the oldest patient had histologically proven immature teratoma with plenty of primitive neuroectodermal derivatives.

Figure 2

(a) Seminoma - dispersed cells against a tigroid background, smudged nuclei and small lymphocytes (H and E, ×400); (b) Yolk sac tumor-vaguely glandular clusters of malignant cells with cytoplasm (H and E, ×400)

Table 3

Cyto-histologic correlation with sensitivity and specificity

There were 14 cases of soft tissue tumors in our study, in which the age range of patients was 2-45 years. The youngest patient had features of neuroblastoma, and the oldest had the feature of pleomorphic sarcoma. Three cases of neuroblastoma were observed in the age group 2-5 years. We encountered one case of paraganglioma [Figure 3a] in a 20-year-old female, which was later confirmed histologically. Smears had the typical features of loose clusters of follicular cells with small round dark nuclei and finely eosinophilic granular cytoplasm. There was mild degree of anisokaryosis, and nuclear chromatin was evenly granular. There were two cases of rhabdomyosarcoma, out of which one had small blue round cells along with few elongated cells arranged in alveolar pattern and was diagnosed cytologically as poorly differentiated carcinoma. Cytologic diagnosis of pleomorphic sarcoma was rendered in eight cases. But histologically, 1 case was of extra-skeletal chondrosarcoma [Figure 3b] two cases were of malignant fibrous histiocytoma and five cases were of pleomorphic liposarcoma.

Figure 3

(a) Paraganglioma-loosely clustered cells with speckled chromatin and resembling follicular arrangement like in thyroid epithelium (MGG, ×400); (b) Extra-skeletal chondrosarcoma cells with moderately enlarged and irregular nuclei, bi-nucleate forms against a background of pale chondroid material (H and E, ×400)

Discussion

According to radiological and cytologic findings, we classified our cases into four groups: renal tumors, retroperitoneal lymphadenopathy, germ cell tumors, soft tissue tumors.

Patients with renal masses were between 1 and 68 years of age, a finding similar to that by Mondal and Ghosh[3] and Ahmed et al.[4] respectively. USG-guided percutaneous FNAC of renal masses was first reported by Kristensen et al.[5] They concluded that FNAC under guidance is required for preoperative diagnosis if there is cystic change in solid renal masses or if the masses are suspected to be malignant. All the smears from renal masses had good cellular yield. Smears from Wilms’ tumor showed a blastemal component with epithelial and mesenchymal differentiation, a finding which was similar to that from the study by Dey et al.[6] Cytologic diagnosis of renal mass in infants is important as preoperative chemotherapy of Wilms’ tumor can reduce the size and may prevent operative rupture and spillage. Cytologic diagnoses were consistent with histologic diagnosis in all four cases of Wilms’ tumor in our study. The findings were in agreement with those from the study by Hazarika et al.[7] Guided FNAC is very helpful for diagnosis, grading and determining operability of renal tumors in adults. Aspirates from renal cell carcinomas showed malignant cells with moderate amount of finely granular vacuolated cytoplasm and macronucleoli. These findings were corroborative with the findings from the study by Renshaw et al.[8]

Cytohistologic correlation was achieved in all the cases of renal cell carcinoma, although cytologic nuclear grading was not compared with histologic nuclear grading (Furhman's). Pilotti et al.[9] studied 132 cases of renal masses, and the results were similar to those of our study.

We got maximum number of cases of retroperitoneal lymphadenopathy in our study; seven cases were cytologically diagnosed as tuberculous lymphadenitis without a need for further histological confirmation.

Amongst the 11 cases of cytologically diagnosed metastatic adenocarcinoma, 9 cases were histologically confirmed. However, we misdiagnosed two cases of diffuse large B-cell lymphoma as metastatic adenocarcinoma; so the sensitivity and specificity was 84.6% and 81.8%,respectively. This is comparable to the accuracy reported by Droese et al.[10] The pitfalls lie in that the large B-lymphoid cells when arranged as diffuse sheets in smears may mimic poorly differentiated carcinoma. The use of markers like cytokeratin and leukocyte common antigen on immunocytochemistry can help to differentiate between lymphoma and adenocarcinoma.[11] Typing of malignancy will help the clinician in deciding the course of treatment. No complications were encountered, which is similar to the finding from studies by Porter et al.[12] FNAC diagnosis of NHL is based largely on monomorphism of smear populations or disproportionate representation of cell types. Cytological typing of NHL in cytology smears is difficult and requires extensive experience.[13]

Amongst the eight cases of germ cell tumors, four were of mixed germ cell tumor, where cytologic appearances varied. Two had predominantly cellular appearance of dysgerminoma, one had the predominant features of yolk sac tumor and one had small blue round cells like in neuroblastoma. But the old age of the latter patient excluded the possibility of neuroblastoma, and few other mesodermal derivatives were seen in smears which helped to diagnose the case as immature teratoma cytologically. The other cases, viz.,that of pure seminoma and yolk sac tumor, had clear-cut cytologic features and were confirmed histologically.

Tao-Negin and Donat[14] have reported a case of primary retroperitoneal seminoma on FNAC with cytologic features of uniform neoplastic malignant cells, arranged singly or in groups of 2-3 cells with round nuclei and round regular nucleoli and clear or pale-staining cytoplasm.

There were 14 cases of soft tissue tumors in our series. Three cases of neuroblastoma were observed in the age group of 2 to 5 years. Neuroblastoma is one of the differential diagnoses of small blue round cell tumor in infants and children and is difficult to differentiate from Wilms’ tumor or embryonal rhabdomyosarcoma. Here the radiological features and characteristic rosettes with pink-staining fibrillary centre helped us to diagnose them as neuroblastoma, which was later confirmed histologically.[15]

Strikingly we encountered one case of paraganglioma in a 20-year-old woman. Smear had the typical features of loose cluster of follicular cells with small round dark nucleus and finely eosinophilic granular cytoplasm. There was mild degree of anisokaryosis, and nuclear chromatin was evenly granular. Alvarez et al.[16] described the cytological features of paraganglioma; background showed hemorrhage and fragments of blood vessels. Cyto-diagnosis of this paraganglioma was later confirmed histologically. In our series, eight cases were diagnosed cytologically as pleomorphic sarcoma, which were later confirmed histologicaly as pleomorphic liposarcoma (five cases), malignant fibrous histiocytoma (two cases) and extra-skeletal chondrosarcoma (one case). Thus, the sensitivity, specificity, predictive value, and accuracy were all 100%, findings similar to those from the study by Mangal et al.[17] Pitfall in cytology is the failure to specifically typify the soft tissue tumors.

Conclusions

We conclude that guided FNAC is very helpful to diagnose the different space occupying lesions early and most accurately with fewer limitations like failure to diagnose the subtypes of sarcoma and the inability to carry out cytologic or nuclear grading of different tumors - possibly due to limited sampling in fine-needle aspiration cytology. The limitations can be overcome by using immunocytochemistry, tumor marker estimation and molecular genetics.