Cutaneous cystic lesions: its clinicopathological correlation with emphasis on unusual ndings.

Background: Cutaneous cysts are the most common lesions encountered in surgical practice with cosmetic and psychological concern to the patient. Aim: To establish the clinicopathological correlation of these lesions and also the importance of histological evaluation for the prevention of misdiagnosing a benign-appearing malignant lesion. Methods: A retrospective descriptive study with data collected from archives of histopathology from January 2018 to December 2020 of clinically diagnosed cutaneous cyst along with age, gender, location and histopathological evaluation were analysed. Results: 88 cases that were clinically diagnosed as cutaneous cysts had a higher female proportion 52.3%. The most common clinical diagnosis is epidermal/ sebaceous cyst. 35.2% of cases were clinically diagnosed accurately but 64.8% of cases did not correlate with clinical diagnosis. 4 malignant lesions were misdiagnosed as benign cutaneous cyst clinically. Conclusion: Most often clinically diagnosed cutaneous cysts are not sent for histopathological evaluation which is a very important tool to confirm the diagnosis.


Introduction
A cyst is an enclosed space or an abnormal sac lined by epithelium containing fluid or semisolid substance within a tissue [1]. Cutaneous cysts are the most common benign lesions presenting as circumscribed dermal or subcutaneous lesions [2].
Most commonly these cysts are clinically diagnosed as sebaceous cysts which is a misnomer and should be regularly confirmed by histopathological examination. A sebaceous cyst is preferably described as either an epidermal inclusion cyst or trichilemmal (pilar) cyst [3,4,5,6].
The most common cutaneous cyst is the epidermal inclusion cyst which is a retention cyst arising from skin appendages, trichilemmal cyst arises from a follicular isthmus of the external root sheath of the hair follicle [6]. Dermoid cysts are also developmental cyst which lacks any entry port and has a predilection for lines of embryonic fusion.
Sweat gland elements may also produce cysts of apocrine or eccrine derivation classified as hidrocystomas [5]. These cysts evoke cosmetic or health problems that are of concern for both the patient and their clinicians where surgical removal is the mode of treatment when indicated.        The dermoid cyst was seen in 6(6.8%) cases which were also clinically diagnosed the same of which two cases showed giant cell reaction. In our study, the face was the common site similar to other studies [3,4]. Cystic hygroma or lymphangioma is a benign congenital malformation of the lymphatic system which is most commonly seen in children and rare in adults. In the present study 4(4.5%)cases of lymphangioma, out of which 2 cases were seen in children and 2 cases was seen in adults which is rare [9,10]. The most common location is the neck region which is similar in our study [10]. Calcinosis cutis is an accumulation or deposition of calcium salts in the skin and subcutaneous tissue [11]. After diagnosing calcinosis cutis, laboratory workup to rule out calcium and phosphorus metabolism, excess vitamin D intake, renal insufficiency, malignancy should be done to identify the underlying cause of the disease [11,12]. In our study 5.6% of cases showed calcinosis cutis and all were clinically diagnosed as sebaceous cyst where inflammation and rupture of epidermoid cyst is the most probable pathogenic mechanism [12,13].
One case clinically diagnosed as a sebaceous cyst without any suspicion of infection was histopathologically diagnosed as a fungal abscess with giant cell reaction, where even after surgical excision, the antifungal drug is the main mode of treatment. Fibroma clinically misdiagnosed as the dermoid cyst was seen in the right index finger also known as cutaneous digital fibroma is a benign fibrous lesion in the dermis [14,15]. Histologically they show proliferation of fibroblast that is uniformly slender with a minimal myxoid component in the dermis which was similar in our study [14].
Eccrine hidradenoma is a benign tumour of the sweat gland which can be either solid or cystic.
Histologically they are well-circumscribed lesions composed of solid and cystic areas, solid area shows polyhedral cells with basophilic cytoplasm or round cells with clear cytoplasm [16,17,18]. Wide surgical excision is the mode of treatment to minimize the recurrence of tumors even though malignant transformation is rare [16]. In our study dual lesion of eccrine hidradenoma with cystic change and the epidermoid cyst was seen (Figure 4).

Figure 4: Eccrine hidradenoma, Cystic and solid area with epidermoid cyst (H&E 10x)
Chondroid syringoma is a rare, mixed tumor of the sweat gland described by Billroth, which reveals differentiation towards the adnexal ductal epithelium with chondromyxoid differentiation in the stroma.
A similar finding was seen in one case which was misdiagnosed clinically sebaceous cyst in our study [19,20]. Though malignant component is also reported in literature only histopathology can help in differentiating it from benign lesion [19].
Cutaneous myopericytoma is an uncommon benign or soft tissue [20,21]. In our study one case was seen which was clinically diagnosed as epidermoid cyst similar to a study by Anug et al which also showed one of the cases diagnosed as a cystic lesion ( Figure 5).

Figure 5: Cutaneous myopericytoma (H&E 10x)
Palisaded encapsulated neuroma is a benign neural tumor in the skin first described by Reed et al [22].
Histologically they are well-circumscribed encapsulated tumor composed of wavy spindle cells arranged in a palisading pattern [22,23]. In our study it was seen in a (60years) elderly patient but it is most common in middle-aged adults as per  [24,25]. A dual lesion with the presence of pigmented pilomatricoma with epidermoid cyst was seen in our study ( Figure   6.a,b).  [25,26,27]. In our study one case which was misdiagnosed clinically as a mucosal cyst in the upper lip was seen in a 34-year female as a solitary lesion [26]. 8(10.4%) cases were benign neoplastic lesions that were misdiagnosed clinically, of which one was a fungal infection that required antifungal treatment.
Few benign lesions have a high recurrence rate where they might need wide local excision and few may require regular follow-up, whereby all these can be diagnosed and could help the clinicians treat the patients appropriately [3,4]. Out of 13(14.7%) clinically misdiagnosed neoplastic lesions 4(4.4%) were malignant histopathologically, of which one was malignant eccrine poroma clinically diagnosed as an epidermoid cyst in the forehead. Malignant eccrine poroma or eccrine porocarcinoma is a rare adnexal tumour arising from eccrine sweat glands.
It was first described by Pinkus and Mehregan in 1963 and accounts for 0.005% to 0.01% of all cutaneous tumors [28,29,30]. The most common age group is the 7th and 8th decade which was similar in our study [28]. Histopathology revealed irregular cord and lobules of polygonal basaloid tumor cells which proliferate asymmetrically with cytological and nuclear pleomorphism, mitosis is seen in the dermis and often invading into subcutaneous tissue is common as seen in our present study (Figure 7). They have a poor prognosis, as local recurrence and metastasis is common [28,31]. 3cases were metastatic lesions of which 2 were papillary carcinoma (Figure 8) of which one was clinically diagnosed as dermoid cyst and the other as cyst wall. 3rd case was histopathologically diagnosed as carcinoma with medullary features which was clinically diagnosed as a thick-walled cyst.  [32]. Histopathology is the main modality in the diagnosis of the above cases without any clinical suspicion of malignancy. Although the possibility of misdiagnosing a malignant lesion as a cystic lesion is very low it has a huge impact on treatment [3,4,7,32].

Conclusion
Most of the cutaneous cysts are correctly diagnosed clinically but there are quite a several cases that are misdiagnosed, as some of the malignant lesions might appear clinically benign, its sequela is huge and irreparable to the patients. Histopathology plays the main role in diagnosing such cases where it highly helps clinicians to decide the treatment plan for the patient.
What new this study adds to existing knowledge?
It is imperative that every cutaneous cyst excised should undergo histomorphological examination although the clinical diagnosis may be an innocuous-sounding sebaceous cyst, as clinical investigation alone sometimes might miss malignant lesions mimicking the appearance of benign lesions.