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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 8  |  Issue : 1  |  Page : 57-61

Utility of fine-needle aspiration cytology in diagnosis of cutaneous and subcutaneous metastasis


1 Department of Pathology, Employees' State Insurance Corporation Medical College and PGIMSR, Bengaluru, Karnataka, India
2 Department of Dermatology, Employees' State Insurance Corporation Medical College and PGIMSR, Bengaluru, Karnataka, India

Date of Submission11-Jan-2021
Date of Acceptance07-Jun-2021
Date of Web Publication26-Jun-2021

Correspondence Address:
Dr. Panduranga Chikkannaiah
Department of Pathology, Employeesf State Insurance Corporation Medical College and PGIMSR, Bengaluru - 560 010, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/amit.amit_8_21

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  Abstract 


Introduction: Cutaneous metastasis (CM) is an uncommon clinical presentation and poses trouble in diagnosis. However, it is remarkable and can occur due to a known or an unknown primary tumor. Despite the fact that clinical assessment helps in the diagnosis, Fine-needle aspiration cytology (FNAC) is a modest, basic, and quick principle line of investigation for the finding of CM. Materials and Methods: It was a retrospective study conducted in the department of pathology at a tertiary care teaching hospital. The study was conducted from January 2010 to May 2020. All cases of CM that has been diagnosed by FNAC were included. Results: During the study period, a total of 37 cases of CM were observed, constituting 0.15% of all FNACs. The age of the patients ranged from 35 to 74 years, and the male: female ratio was 1.05:1. Primary tumor was known in all 37 cases. Among males, lung carcinoma was the more common whereas breast was the most common organ of primary among females. The most common lesion was a single nodule (27 cases), with predominant site being chest wall (32.5%), and the most common tumor at microscopy was metastatic adenocarcinoma. Conclusion: FNAC is a fast and safe procedure that can be utilized as a first line of investigation in diagnosing metastatic skin lesions. Basic assessment of cytomorphology alongside significant clinical subtleties could help in recognizing the site of an unknown primary.

Keywords: Adenocarcinoma, cutaneous metastasis, fine-needle aspiration cytology, lung carcinoma, squamous cell carcinoma


How to cite this article:
Nair N, Chikkannaiah P, Venkataramanappa S, Shivanna R. Utility of fine-needle aspiration cytology in diagnosis of cutaneous and subcutaneous metastasis. Acta Med Int 2021;8:57-61

How to cite this URL:
Nair N, Chikkannaiah P, Venkataramanappa S, Shivanna R. Utility of fine-needle aspiration cytology in diagnosis of cutaneous and subcutaneous metastasis. Acta Med Int [serial online] 2021 [cited 2021 Oct 21];8:57-61. Available from: https://www.actamedicainternational.com/text.asp?2021/8/1/57/319438




  Introduction Top


Cutaneous metastasis (CM) denotes tumor invasion of the skin from a known or obscure primary and conveys a poor prognosis. Early determination is significant to provide treatment to such patients. Literature review shows that the rate of CM ranges from 0.7% to 10.4%.[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] It can be manifested as a late secondary lesion or an early recurrent lesion to a known primary and rarely the only manifestation of an unknown primary. The rate of CM increases with age and more so after 50 years. The most common malignancies to show secondaries to skin are breast, lung, and gastrointestinal tract (GIT). Patient benefit demands early diagnosis which requires high clinical suspicion.[2]

CM with unknown primary poses a diagnostic challenge to a clinician and pathologist. Fine needle aspiration cytology (FNAC) is an out patient technique, it is simple and reliable. When applied this technique will help to differentiate CM from primary cutaneous tumours.[13],[14] The present study is to establish the utility of FNAC in the diagnosis of CM lesions.


  Materials and Methods Top


It is a retrospective study conducted in the department of pathology at a tertiary care teaching hospital. All cases of CM that has been diagnosed by FNAC in our institute from January 2010 to May 2020 were included. Patients with primary malignant adnexal tumors were excluded.

Sample size was calculated using the following formula: n = Z2αpq/d2 where Zα is 1.96, P = 70%, q = 100 − 70 = 30, and L = 15. With the above formula, the minimum sample size was 35, but during the study period, we were able to collect 37 samples. Demographic profiles of the patient such as age, sex, site, and primary tumors were retrieved from the cytology request and medical record sections. Cutaneous location of the lesion was confirmed by radiological examination. Cytology slides were retrieved from the pathology archives and reanalyzed. It is our practice that, for every case, we do FNAC using a 23G needle with a 5-ml disposable syringe attached. Two or three passes were required for adequate material. Five to six slides were prepared. Air-dried smears were used for Leishman's staining. Alcohol-fixed wet smears were used for hematoxylin and eosin stain and Papanicolaou (PAP) staining using standard protocol. The study is approved by the institutional ethical committee bearing no. 532/l/11/12 dated December 2, 2020.

Statistical analysis

Statistical analysis was performed using frequency and percentage.


  Results Top


During the study period, a total of 24,129 FNACs were performed, out of which 37 cases of CM were observed, constituting 0.15%. The age of the patients ranged from 35 to 74 years. The diseases are common after the fourth decade, with 26 cases in the age range of 35–74 years [Table 1]. Males were slightly more affected than females (male: female: 1.05:1). Among females, breast carcinoma was the most common primary site, constituting 35%, whereas lung carcinoma was most common in males accounting for 24%. Chest wall is the most common site of occurrence in 32.5% followed by back in 8 (21%).
Table 1: Age distribution of cases

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Single nodule was observed in 27 (73%) cases, more than one nodule were noted in 7 (20%) cases, and in 2 cases (5.5%), papule was noted and 1 case had ulcer (2.5%) [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d.
Figure 1: Clinical photograph of cutaneous metastatic lesion, note the single nodule (a and d), multiple nodules (b), and ulcerative lesion (c). (e and f) Microphotograph showing clusters of ductal cells with malignant features (red arrow) (Giemsa × 40). (g) Microphotograph showing clusters of glandular cells with malignant features in the background of necrotic material (arrow) (Giemsa, ×10). High magnification of the same image (h) (Giemsa, ×40). (i) Microphotograph showing clusters of malignant squamous cells in a dirty background (arrow) (Papanicolaou stain, ×10). High magnification of the same image (j) (Papanicolaou stain, ×20). Microphotograph showing clusters of squamous cells with malignant nature (Giemsa, ×40). (k) Microphotograph from a case of cutaneous metastasis of lymphoma showing mono- to biomorphic population of lymphoid series cells (Giemsa, ×40) (l)

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Adenocarcinoma (including invasive ductal carcinoma-no special type) was the most common microscopic pattern in 24 (65%) of cases followed by squamous cell carcinoma in 8 (21.5%) cases. Two cases (5.5%) of NHL and one each case of hepatocellular carcinoma, follicular carcinoma, and pleomorphic sarcoma were noted. In the present study distant metastasis was observed in three cases (1. Carcinoma lung to right leg, 2. Carcinoma carvix to neck, 3. Soft tissue sarcoma of thigh to face).

In all the cases, the primary tumor was known. Out of 37 cases, in 35 cases, CM was the late manifestation, and in 2 cases, it has preceded the primary malignancy. The clinical and pathological details of cutaneous and subcutaneous metastasis are shown in [Table 2].
Table 2: Clinical and pathological details of cutaneous and subcutaneous metastasis

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Smears from adenocarcinoma showed clusters of tumor cells with increased nuclear-to-cytoplasmic ratio, hyperchromatic, pleomorphic nuclei with prominent nucleoli, and moderate [Figure 1]e, [Figure 1]f, [Figure 1]g, [Figure 1]h cytoplasm. Tumor cells are also arranged in glandular pattern. Squamous cell carcinoma shows scattered to clusters of tumor cells with vesicular, pleomorphic nuclei with basophilic cytoplasm [Figure 1]i, [Figure 1]j, [Figure 1]k. Cases from lymphoma showed scattered monomorphic lymphoid series cells with occasional cells showing nuclear indentation [Figure 1]l. Metastasis from the thyroid showed tumor cells arranged in microfollicular pattern. Hepatocellular carcinoma cells showed glandular cells with abundant granular cytoplasm. Smears from sarcoma showed spindle cells with malignant nature.


  Discussion Top


Skin is the largest organ in the body, however it is the rare site of metastasis with a prevalence of 0.7%–10. 4%.[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16] Lookingbill et al.[1] and Spencer et al.[17] in their autopsy study on visceral malignancy observed a higher incidence of 9%–10%. In the present study, we have observed a prevalence of 0.17% and our findings were consistent with Sharma et al.[6] and within the range reported in the literature[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16] [Table 3].
Table 3: Comparison of clinical and pathological findings of cutaneous and subcutaneous metastasis with published literature

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CM is of diagnostic challenge and carries a poor prognosis. In some cases, it will be the first indication of metastasis in an adequately treated cancer, or the first manifestation of an occult primary. Occurrence of CM simultaneously with the primary tumor will alter the staging and treatment plan.[7]

CM can occur at any age; in the literature, it has been observed in the range of 2–90 years; and in the present study, it was in the range of 35–74 years and is consistent with the literature[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15] [Table 3]. Males are commonly affected than females and the same was also observed in the present study. In contrast, Mendonca et al.[11] and Nibhoria et al.[10] observed female predominance. Chaudhury et al.[9] and Sharma et al.[12] in their study observed no gender difference.

Incidence of tumor metastasis to skin correlates with the frequency of occurrence of primary tumors in each gender. Among the females, breast was the most common primary organ and same also been observed in the present study.[3],[4],[5],[6],[7],[9],[10],[11],[13],[14],[15] In a study, Chaudhury et al.[9] observed hematological and Sharma et al.[12] observed GIT as the most common primary organ among females. With respect to males, the primary organ varies among studies. In the present study, lung is the most common primary site and our findings were in consistent with Srinivasan et al.,[3] Gupta and Naran,[4] Sharma et al.,[6] Karki et al.,[8] Mendonca et al.,[11] Nibhoria et al.,[10] Handa et al.,[13] and Rajasree Varma et al.[15] In a separate study, by Bansal and Naik[5] and Bansal et al.[7] observed that GIT has the most common primary organs among males. In a study, Chaudhury et al.[9] observed that hematological malignancy as the most common primary site. Gupta et al.[14] observed that gallbladder as the most common primary site.

In the present study, the most common site of involvement was chest followed by abdomen and our findings are in consistent with the literature.[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15] Due to the lymphatic spread of tumour, CM occurs near to primary organ however due to the haematogenous spread of tumor distant sites can be involved. Metastasis occur by both lymphatic and haematogenous route. When occur by lymphatic route surrounding and near by skin is involved. Example for lymphatic route are carcinoma lung and breast metastasizing to back. Gastrointestinal carcinoma to umbilicus and renal cell carcinoma to lumbar region. Distance metastasis occur due to hematogenous route. In the present study three cases showed distant metastasis. Gupta et al.[14] in their study observed three cases of distant metastasis: carcinoma cervix metastasizing to arm, renal cell carcinoma metastasizing to shoulder, and testicular cancer metastasizing to back. Nibhoria et al.[10] observed only a case of carcinoma cervix showing metastasis to thigh.

Clinically CM occurs as a single nodule and rarely as multiple lesions. The morphological spectra of clinical appearance described in CM were papules, nodules, plaque, tumors, telangiectatic lesions, and ulcers.[13] In the present study, thirty cases were single lesions and seven cases had multiple lesions. Morphologically predominantly were nodules (34 cases) followed by 2 cases of papules and one case of ulcerative lesion were observed and our findings were consistent with literature[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15] [Table 2]. In a study by Ayyamperumal et al.,[16] multiple sites were common than single lesions.

Among 37 cases, 35 had a prior history of malignancy, and in two cases, CM was diagnosed along with the primary tumor. None of the cases were unknown in the present study. Our findings were similar to Bansal et al.[7] and Nibhoria et al.[10] However, many authors have dealt with unknown primary cases.[3],[4],[6],[8],[9],[11],[12],[13],[14],[15] The comparison of clinical and pathological findings of cutaneous and subcutaneous metastasis with published literature is shown in [Table 3].

CM occurring as single nodule and unknown primary are diagnostic challenge to dermatologist and pathologist. In this situation, primary adnexal tumor forms the close differential diagnosis, and can be differentiated on the basis of morphology and with the help of special stains and immunohistochemistry. Adnexal tumors with clear cell morphology such as hidradenoma or sebaceous neoplasm mimic like renal cell carcinoma. Renal cell cancer will be periodic acid–Schiff-positive and diastase-sensitive reaction. Metastatic squamous cell carcinoma will show positive reaction on PAP stain and negative oil red O stain and thus can be differentiated from adnexal tumor with squamous cell differentiation. Most difficult is to differentiate metastatic adenoicarcinoma with adnexal tumor showing sweat gland differentiation. Metastatic tumor will show signet ring cells, extracellular mucin along with three-dimensional clusters of tumor cells.[13] Most of the primary adnexal tumors will also have intermingled benign component.[10]

Carcinomas have more propensities for metastasis than sarcoma. Carcinomas such as lung, breast, GIT, germ cell tumors, melanomas, and hematolymphoid malignancy were common. Sarcomas such as Ewing's sarcoma, osteosarcoma, leiomyosarcoma, epithelioid sarcoma, chondrosarcoma, and angiosarcoma have been reported with CM. In the present study, we have observed only one case of pleomorphic sarcoma metastasing to face.[13]

FNAC also helps in predicting the probable primary site of metastasis, in cases of unknown primary. Signet ring cells with intra and extracellular mucin points the primary towards GIT. Card-like arrangements of single cells suggest carcinoma breast. Cells with microfollicle arrangements suggest thyroid. Melanoma will show brownish pigment with prominent eosinophilic nucleoli with spindle to plasmacytoid cells. Cytoplasmic elongation with abundant cytoplasm is seen in transitional cell carcinoma. In difficult cases, immunohistochemistry will help to predict the unknown primary.[10],[15]


  Conclusion Top


CM is a rare entity and lung carcinoma in male and breast carcinoma in females, were the most common primary organ and chest being the most common secondary site. CM with unknown primary will cause diagnostic challenge. FNAC is a fast and safe procedure that can be utilized as a first-line of examination in diagnosing metastatic skin lesions. Basic assessment of cytomorphology alongside significant clinical subtleties could help in recognizing the site of an unknown primary.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Bansal R, Naik R. A study of 70 cases of cutaneous metastases from internal carcinoma. J Indian Med Assoc 1998;96:10-2.  Back to cited text no. 5
    
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Karki S, Pathak R, Manandhar U, Koirala S. Metastaticcutaneous and subcutaneous lesions: Analysis of cases diagnosed on fine needle aspiration cytology. JPN 2011;1:37-40.  Back to cited text no. 8
    
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Mendonca B, Fernandes H, Rahim S, Ali S, Hegdekatte N. Fine [11]needle aspiration cytology – A boon in the diagnosis of cutaneous and subcutaneous metastatic nodules. Int J Recent Trends Sci Technol 2015;14:455-7.  Back to cited text no. 11
    
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Gupta B, Mallya V, Jain S, Agarwal PN. Utility of FNAC in dermatological manifestations of metastatic cancer with the review of the literature. J Cytol 2018;35:237-41.  Back to cited text no. 14
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