A clinico-histopathological study of cutaneous appendageal tumours

Introduction

More than ten decade ago, the noted pathologist Rudolph Virchow understood skin as a protective covering for more delicate and functionally sophisticated internal viscera 1 .The skin is a complex and largest organ in the human body, Cutaneous appendageal tumors are basically classified into following groups viz., arising from hair follicles, sebaceous glands, & ducts(eccrine glands and apocrine glands) 2.These tumors mainly arise from the undifferentiated pluripotent stem cells and differentiate to specific tumors influenced by genetics, local vascularity and microenvironment of the epidermis and dermis 3 . These tumors commonly present with papule and nodules. Mainly present on head-neck region, but also can present elsewhere in the body 2 . Usually appendageal tumor s are benign rarely malignant, cutaneous appendageal tumors were presented clinically with papules or nodules, sometimes with ulcers. This produce confusion in the nomenclature and difficulty in diagnosis and treatment 2 . Therefore, histopathological confirmation will playa very important role in the accurate diagnosis of the disease 3 . The Risk of malignant degeneration has been varies with individual lesions 1. The local recurrence is well recorded but events metastases are rare with the exception of the malignant eccrine and apocrine gland derived tumors and sebaceous carcinoma 4 . Sometimes due to morphological overlap of the lesions, malignancies are missed out. Thus, this study can attempt to correlate early diagnosis of malignancy with respect to treatment aspects and also to know the relation between clinical features and histopathological features of cutaneous appendageal tumors and to describe the diagnos is of malignancy at early stage, the incidence of various benign and malignant appendageal tumors were significantly correlate with the clinical features in relation to age and sex matched frequency with various histological types of tumors etc..

Materials and Methods

A prospective observational study was conducted at Department of Dermatology, Kempegowda Institute o f Medical Science and Research, Bengaluru during the year 2014-2016. A total 100 clinically suspected patients were recruited with written consent. All patients were met inclusion and exclusion criteri. Inclusion; Benign and malignant tumors of the cutaneous appendages. Age group of patients between 18 -70 years. Exclusion; Benign and malignant tumors of the epidermis and subcutaneous fat, Tumors of melanogenic system were excluded from the study, The hematolymphoid tumors, soft tissue tumors and metastatic tumors, pregnant, lactating mothers and children and Patients those who does not give the consent population excluded. The Skin appendageal tumors were evaluated by taking consent of the patient’s, the detailed history was extracted from the patient record, clinical examination biopsy was done for all patients’s. Patient were examined thoroughly and asked to stop blood thinning drugs four days prior to the procedure, also data sets of Type -II diabetes mellitus (uncontrolled leads to secondary infection of biopsy site and delays wound healing of the biopsy site) and other comorbidities were collected from the pretested questionnaires. Local anaesthesia was administered by using lignocain 1/80000 dilution with norm al saline using insulin syringe, 2.5 mm or 3 mm biopsy test was used to extrapolate the lesions, even excision biopsy was done for the bigger lesions and suture was done with ethylon 4’0 suture material if necessary. Biopsy tissue was sent for histopathological examination to pathology department. Patient was administered on short course of oral and topical antibiotics. The collected data was analyzed by using SPSS-16.50 version. Chisquare test, ANOVA, paired and unpaired t test statistical methods was employed to test the hypothetical results.

Results

A Total 100 cases were cutaneous appendage tumors were seen in study period. Of these 100 cases, 95 cases were benign and 5 cases were malignant tumors. Benign tumors constituted 95.0% and malignant tumors constituted 5.0%. The study showed female predominance, male to female ratio was 75:25 . Study shows that, the most of the cases presented with multiple papules, followed by single papule and nodules. Face (periorbital, malar check) is a common site of involvement in cutaneous appendageal tumors. An a pocrine gland tumors were seen in 65 cases (65.0%), eccrine gland tumors were seen in 73(73% ). only one cases expressed eccrine duct tumors (1.0%). The H air follicle tumors were comprises 20.0% of the cases,1 case of spiroadenoma were seen in male patient at the median age of 56 (IQR 52-58) years of age, presented as multiple papules on the extensor aspect of the right forearm. Histopathology findings showed that, the thinned outepidermis with focal area of necrosis and ulceration. The papillary dermis shows an adnexal tumor demarcated from overlying epidermis by a clear grezzone. Tumor had composed of nest and lobules of tumor cell with little pleomorphism and moderate amount of pale eosinophilic cytoplasm. Largenuclei with prominent nucleoli, moderate anisonucleosis and atypical mitosis. sebaceous carcinoma has noticed in one female (1.0%) at onset of 65 years, presented with nodule scalp (p<0.001) it was found to be statistically significant. The tumor arranged in lobule and syncytial pattern with scant stroma was seen in study period. Tumor cells are large polygonal with moderate amount of foamy cytoplasm, vesicular nucleus and prominent nucleoli. Syringocystadenoma papilliformis was seen in one male patient at the onset of 40 years of age presented with plaque on the scalp since 15 years with no symptoms (p<0.01). A Similar study findings were noticed during the study intervention, an etramammary paget’s disease was expressed with prevalence of 1.0 %, exhibits at the onset of 66 year of old female (p<0.01) presented with plaque in left axilla with ulceration since two years (p<0.01). Nearly three (3.0%) cases of pilomatricoma were encountered and found to be statistically significant (p<0.01) (1 male and 2 females 1:1) IQR age (38 -40 years). In the present study maximum of the cases of tumors were of eecrine gland accounting for 73.0% (odds 5.30-7.55 MLE’s 21.56) p<0.01, followed by hair follicle 20% (odds 1.25-3.55,MLE ’ s 8.11) p<0.01, followed by apocrine glandr 6% (odds 0.52-1.44, MLE’s 0.62) p>0.01, followed by eccrine duct origin was seen in one patient 1.0% (odds 0.21-0.55) p<0.01. The study shows that, out of 100 cases of appendageal tumors, only 39 cases were seen during study period (39%) (odds 10.15-16.22,MLE’s 16.11) p<0.01 cases were significantly correlating with clinically and histopathologically findings as compared with rest of the population. (63/100)

Figure 1

Syringoma over neck

Figure 2

Syringoma on face

Figure 3

Trichoepithelioma

Figure 4

Eccrine hydrocystoma

Figure 5

Apocrine hydrocystoma with syringoma

In the present study benign tumors formed the majority (95%). In the study by Sharma A et al and Ackerman BA et al benign tumors formed the majority Apocrine/Eccrine tumors (79%) was commonest which is consistent with finding of Deprez M 3 .

The sensitivity of clinical diagnosis versus histopathological diagnosis for non syringoma was 52/100 and Syringoma 48/100 is significantly associated with clinical diagnosis as accruded with good specificity (88.46 % ) PPV (80.65%) and NPV (66.67%) p<0.0001. However, the accuracy of the test diagnosing of both true positive and true negative predictive values by obtaining clinical and histopathological for syringoma (71%). The results were found to be significant lyassocia ted between clinical and histopathological diagnosis. Chi-square 19.183,(P<0.001). Similar homogeneous findings were noticed in Trichoepithelioma (50.0%) (p<0.01), non-trichoepithelioma was 88.63% (p<0.01) with moderate specificity of the test (37.50% ) of the 12 cases of trichoepithelioma was the positive predictive value PPV (92.86%) of non-trichoepithelioma was the negative predictive value. However, the accuracy of the test diagnosing of both true positive and true negative values obtaining from the resulted findings as significantly associated with histopathologically findings trichoe pithelioma (84.00%). It was found to be highly significant association between clinical and histopathological diagnosis,(P<0.003) coefficient of determination was (R2=0.98). The same extension of the resulted findings were noticed in the cylindroma, the sensitivity of clinical diagnosis versus histopathological diagnosis of cylindroma was 33.33% ie 33.33% of cases were diagnosed clinically and histopathologically, where as true negative - non-cylindroma was 100.00%, which is the specificity of the test was 100.00% of 3 cases of cylindroma was the positive predictive value (PPV).

The sensitivity of clinical diagnosis versus histopathological diagnosis for eccrine hydrocystoma was 28.57% (P<0.01). ie a total 28.57% of cases were diagnosed clinically and histopathologically, true negative i.e non-eccrine hydrocystoma was 97.83% which is the specificity of the test. 50.00% of the 7 cases of eccrine hydrocystoma was the positive predictive value, 94.74% of non-eccrine hydrocystoma was the negative predictive value. However, the accuracy of the test diagnosis of both true positive and true negative by clinical and histopathologically for eccrine hydrocystoma was (92.00%). It was found to be highly significant association between clinical and histopathological diagnosis (P<0.024). The nodular hidradenoma, paget’s disease of nipple, sebaceous carcinoma and syringocystadenoma were highly statistically significant differences were observed with respect to good specificity and sensitivity (>95%) (p<0.01).

Discussion

Appendageal tumors are thought to have a genetic basis. Mendelian inheritance and P-53 mutations are important contributing factors. Cell of origin is supposed to be from either primary epithelial germ cell or pluripotent cells or cells of pre-existing structure. Primaryepithelial germ cells may give rise to either hyperplasia or neoplasia 1. Clinically cylindroma occurs in forehead and scalp, syringoma as multiple, small, tiny papules in the vicinity of lower lids4. Trichoepithelioma usually occur as multiple, semi transparent dome shaped papules on the face, scalp, neck and upper trunk. Sebaceous carcinoma occurs in the meibomiam glands of eyelids Grossly adnexal tumors are non descriptive, seen as papules, solitary or multiple, as flesh coloured nodules and disfiguring lesions such as ulcers.

Adnexal tumors of the skin, though rare have been recognized from the later part of the 19^th century. We also observed that, the adnexal tumors of skin appear to be relatively uncommon tumors. Of the 100 cases studied, benign adnexal tumors were more commonly seen in malignant tumors.8 6

There are only a few studies from India and abroad describing in detailed about the appendageal tumors of the skin. In the present study, syringoma was the most common appendageal tumor of sweat gland origin accounting for 48%, spiradenocarcinoma, microcystic adnexal tumors, sebaceous carcinoma, syringe cystadenoma papilliferum, extramammary pagets and paget’s disease of the nipple are the least common tumors observed in the present study. Syringomas are characterized histologically by interweaving nests, cords and small cysts that are located in the upper half of the dermis. They are enmeshed in a dense collagenous stroma without any epidermal contact. The ducts of syringoma are composed of 1-2 layers of cuboidal cells rarely showing clear cell change. Tadpole appearance is quite common in syringoma9,6,10,11,12.

Though sebaceous carcinoma was common in an earlier report, only single case observed in the study. Histologically, sebaceous carcinomas have infiltrated zones and often harbour pleomorphic cell populations of clear and solid cells. Trichoepithelioma were reported in 12% of the cases in the present study. Histologically it is a symmetric lesion that contains a mixture of epithelial elements ranging from hair germs associated with capillary mesenchymal bodies to small horn cysts, to lace like reticular basaloid structures to mature hairs 10 . It is striking that only 39 out of 100 cases showed clinical and histological correlation11 . This indicates cutaneous appendageal tumors cannot be diagnosed on clinical grounds only and histopathologic diagnosis plays a major role in diagnosing these tumors. In dermatopathology, one of the most intriguing yet unresolved question is the lineage of appendageal neoplasms with an expanding arsenal of stem cell markers 13,14,15,16 . Similar study literature has correlated with the present study intervention

Conclusion

Skin is a complex organ. Because of its complexity a wide range of diseases can develop from the skin including tumors from surface epidermis, epidermal appendages and dermal tissue. The diagnosis of skin tumors presents unique difficulties, in part, related to the wide variety of tumors and the complicated nomenclature. The study of histogenesis of the adnexal tumors is interesting, fascinating and challenging because of wide range of differentiation. Histopathological study is one of the most valuable means of diagnosis in dermatopathology and the diagnosis of skin tumors can be done by correlating clinical features, grossandhistological appearances. The present study emphasizes the various patterns of cutaneous appendageal tumors in this varied geographic location in Indian context. Histopathological confirmation is mandatory for any cutaneous appendageal tumors for accurate diagnosis and early treatment in case of malignancy.

Funding

None.

Conflict of Interest

None.