Diagnostic Significance of Fine Needle Biopsy and Cell Block in Skin and Subcutaneous Nodules

Diagnostic Significance of Fine Nee dle Biopsy and Cell Block in Skin and Subcutaneous Nodules. Evaluation of patients with cutaneous or subcutaneous nodules, especially if they are multiple, is a diagnostic challenge. This study aimed to investigate smears and cell blocks and compare them with examination of tissue biopsies. Fine needle aspiration cytology (FNAC) and cell blocks were done for 225 cutaneous and subcutaneous nodules. Furthermore, histopathological examination was conducted using biopsies. Results: According to tissue biopsy, benign lesions constituted the most common finding in 180 (80%) cases. The detected cases were lipoma in 35 (15.5%) cases, adipose tissues in 30 (13.3%) cases, 20 fibro lipomas (8.8%), 20 fibromas (8.8%), 5 juvenile fibroma (2.2%), neurofibroma in 5 cases (2.2%), sebaceous cyst in 25 cases (11.1%), implantation cyst, or dermoid cyst 20 cases (8.8%), pilomatrixoma 5 cases (2.2%), seborrheic keratosis10 cases (4.4%) and Madura foot (actinomycosis) in 5 cases (2.2%). Intermediate lesions of atypical lipoma were found in 20 cases (8.8%). were 25 cases (11.11%) as follows: 10 cases (4.4%) basal cell 10 cases (4.4%) squamous cell and 5 cases (2.2%) basosquamous cell For FNAC smear examination, the sensitivity test was and the specificity was 16.66%. For cell blocks the sensitivity and specificity tests were and 100%, respectively.


Introduction
Skin and subcutaneous lesions are a common reason for patients to visit family doctors. Ultrasound is increasingly being used to confirm the diagnosis, but deep lesions must be evaluated with magnetic resonance imaging (MRI) or computed tomography (CT) to exclude invasion of the underlying structures and/or malignancy [1]. People can experience a wide range of growths and skin changes over the course of their lives. Family physicians must be able to distinguish between different skin tumors specially to rule out malignancy [2]. Skin malignancy represents one of the most dangerous types of cancers. It spreads gradually in its early stages, so it is necessary to detect it as soon as possible. It is suggested that skin cancer results from the presence of unpaired strands of deoxyribonucleic acid (DNA) in skin cells, resulting in skin genetic defects or mutations [3]. Evaluation of patients with skin or subcutaneous nodules, especially if they are multiple, is a major problem for clinicians. But with full investigations, the problem becomes easier. However, the definitive diagnosis depends on the pathological reports of tissue biopsy [4]. Easy access to skin nodules provides a good platform for performing fine needle cytology and sampling by pathologists or clinicians. Smear cytology gives several default settings [5]. Depth is more important than width. The skin nodule may be mobile or fixed in the underlying tissue. Proper management of skin or subcutaneous nodules needs to know their exact nature, benign or malignant. These nodules can be accessed through needle aspiration, to make smears and cell blocks; this action is relatively non-invasive outpatient procedure and does not require an operating room or anesthesia. It is also a cheap and fast process. Furthermore, it has been suggested that FNAC breast exam is very useful, relatively quick, inexpensive and less invasive test due to the size of the fine needle, and is easier and safer in some lesions, such as very small lesions or those directly under the skin [6]. The question was how is his sensitivity and specificity, and to what extent can he be relied upon in making a treatment decision? Therefore, this study aimed to verify the reliability of examination of smears and cell masses in the diagnosis of skin and subcutaneous nodules and to compare them with examination of tissue biopsies.

Study Design and Samples' Preparation
Samples of cutaneous or subcutaneous nodules from two hundred and twenty-five patients who decided and gave written consent to participate in the study were selected for this study. These patients were referred from various related clinics in University Hospitals to the Department of Pathology between January 2018 and December 2020. The patients underwent full history taking, general examination for pulse, temperature, respiration rate, body weight, and height. All malignant nodules were primary lesions.
The nodules under study were examined clinically for location, size, plurality, shape, consistency, color, if hair was present or not, and whether there was change in color, size, shape, mobility or fixation.
Then, a sterile 10 cc plastic syringe was opened, approximately 1 cc of air was taken, the cover was placed on the needle and it was ready for use. The lesion and the surrounding skin underwent a gentle massage with cotton gauze filled with 95% ethanol, then the needle was inserted close to the periphery of the node (avoiding the center where there may be necrotic material that hinders proper smear taking). The needle was moved in multiple directions with suction; then it was gently removed. Then, the suction site was under pressure with clean, sterile cotton gauze for at least 10 minutes to stop possible bleeding. The needle was gently removed from the syringe, and then 1 drop of the syringe's content was placed on approximately 4 clean glass slides. The smear was prepared by gently moving the blunt end of the syringe.

Discussion
In this study, we focused on the performance of cell mass and its importance in diagnosing and differentiating lesions due to its simplicity and reproducibility. We performed FNAC smear first, as it is a rapid test to detect the presence and types of cells in general and also to compare the features found in FNAC smear and those in cell blocks. FNAC is an easy to perform and inexpensive technique.
It does not disturb the architecture of the lesion and has nothing to do with the promotion of metastasis of malignant lesions, because it is a non-invasive technique and does not harm the patient. It looks similar to intramuscular or subcutaneous injection of any medication using a fine needle. We utilized the clot method for preparation of cell blocks, other methods described by [9] and [10].
We preferred the clotting method because the structural forms of cells and tissues were more preserved. We utilized the same clotting method in preparation of cell blocks in two previous studies and gave excellent results [11]. Patients in this work ranged in age from 2 to 76 years with a greater transition to senescence (>40 years was about 70%), and the female to male ratio was 3 to 2, respectively with no significant outcome. This means that the appearance or complaint of the skin or subcutaneous nodules occurs more often in females and at older ages. For FNAC smear results, the test processed a sensitivity about 83% that is a significant percentage but lower than that of cell block (97.77%) This meant that cell block is more sensitive test than FNAC smear. Furthermore, cell block technique is more specific than FNAC smear, (100%) for cell block, and 16.66% for FNAC smear).
These results alluded to the role of cell block in appearance of cell orientations which give a picture resembling the tissue biopsy.
Similarly, another study reported high sensitivity and specificity of FNAC in diagnosing skin lesions with sensitivity of up to 100% in epidermal cyst and inflammatory lesions, but showed only 67% for adnexal tumors [12]. The authors also reported specificity of 50% for adnexal tumors.In case of benign cyst, the cyst was filled of fluid, This picture gives a confidence in diagnosis as a benign lesion. In cases of lipoma and fibrolipoma, the smear showed fat globules and/or mature fat cells, fibrous elements a picture found by other authors [13]. These features give a confidence of benign lesion, but the specific diagnosis cannot be achieved. The specific diagnosis of lipoma, fibrolipoma can be given easily in cell block. In cases of fibroma; the smear gave a suggestion of benign fibrotic lesion (spindle-shaped fibroblasts and some collagen fibers), but the cell block showed well-formed fibroma. In cases of juvenile fibromas, the smear may be negative because of the dense contents; however, the cell block is specific for diagnosis, moreover, it takes another importance to exclude juvenile fibrosarcoma and fibromatosis (the absence of mitotic activity).
On contrary of the previous lesions, FNAC smear provided satisfactory results that distinguished a benign lesion, and also specific for neurofibroma; because it gave us a picture of twisted nuclei, angulated and a hair-like background of neurofilaments a feature also found by [14]. In cases of pilomatrexioma, the smear gave a picture of benign lesion (ghost cells, mature epithelial cells, giant cells) the same picture found by [15], but the cell block failed in most cases because of the presence of admixed amounts of degenerated, or shadow cells. In cases of dermoid cysts or implantation cysts, the smear showed a mixture degenerated epithelial cells and keratinous material, a picture found also by [16], but the cell block also usually failed due to the keratinous material.In cases of atypical lipomas, FNAC smear showed a very useful picture; pleomorphic, hyperchromatic lipoblasts, mucoid background; the cell block did not add a more information. In cases of basal cell carcinoma; FNAC smear showed malignant cells with basophilic cytoplasm; the same results were found by [17], but the orientation of cells appeared in the cell block with peripheral palisading. In cases of squamous cell carcinoma, the malignant epithelial cells and the individual cell keratinization appeared in the smear. The FNAC smear showed a good picture but the specific feature of cell nests and keratin pearls appeared in the cell block. In cases of FNAC smear of basosqaumous cell carcinoma; the smear gave a picture of malignant epithelial cells, but the specific orientation of basosqaumous cell carcinoma appeared in the cell block,In cases of Madura foot, the smear showed mixed inflammatory cell infiltrate which was non-specific, but cell block was very useful to clarify the mycetoma colonies with appearance of peripheral esinophilic clubs; however, [18] could found this feature in the FNAC smear. The flowchart followed in the study and the main results are shown in Figure 11.

Conclusion
Cell block study gives a more specific and more orientation of the cells similar to that of tissue biopsy. FNAC smear may give a useful advantage. Some lesions give negative results in smears, others give negative results in cell block. Therefore, we recommend performing FNAC smear as well as cell blocks whenever possible.