HISTOPATHOLOGICAL EVALUATION OF CHRONIC NON HEALING ULCERS OF SKIN IN PATIENTS REFERRED TO TERTIARY CARE HOSPITAL IN KASHMIR.

of age. Lupus Vulgaris was found to be the commonest form among the tubercular ulcers constituting 75% of the tubercular ulcers followed by Scrofuloderma accounting for 25% of the cases. Among malignant cases, that Squamous cell carcinoma is the most common variety of malignancy encountered in an ulcer accounting for 82% of cases followed by Basal cell carcinoma 14% and malignant melanoma 4%. Conclusion: Non-healing ulcers can be encountered at any age and etiology may vary from one geographical region to other and may also be different in different racial groups. Thus beside a good clinical diagnosis, early biopsy to rule out malignancy and identify the etiology is mandatory for a better outcome and minimize the morbidity and mortality among patients with non-healing ulcers.


ISSN: 2320-5407
Int. J. Adv. Res. 6(2), 1885-1890 1886 of age. Lupus Vulgaris was found to be the commonest form among the tubercular ulcers constituting 75% of the tubercular ulcers followed by Scrofuloderma accounting for 25% of the cases. Among malignant cases, that Squamous cell carcinoma is the most common variety of malignancy encountered in an ulcer accounting for 82% of cases followed by Basal cell carcinoma 14% and malignant melanoma 4%. Conclusion: Non-healing ulcers can be encountered at any age and etiology may vary from one geographical region to other and may also be different in different racial groups. Thus beside a good clinical diagnosis, early biopsy to rule out malignancy and identify the etiology is mandatory for a better outcome and minimize the morbidity and mortality among patients with non-healing ulcers.
General surgical referral guidelines defines any non-healing ulcer as that which has been present for 3-4 weeks duration and has not responded to conventional therapies 1 . Sometimes a need of surgical intervention is forced upon. Although histopathology remains the gold standard for most dermatologic diagnoses, it must be recognized that not all lesions are amenable to definitive "specific" histologic diagnosis 2 .
Chronic wounds are characterized clinically as wounds that have failed to proceed through a biologically predictable and timely healing process and either are unresponsive to initial therapy or persist following appropriate wound care 2-3 They are often identified by the presence of a raised, hyperproliferative, yet nonadvancing wound margin 2,3 . Understanding the pathological alterations of wound tissue that are refractory to standard wound therapy is essential for effective wound management and healing. The presence of a chronic wound can result in significant morbidity or mortality.
Chronic cutaneous ulcers are common in the developing countries like India, especially in rural areas with poor living conditions. These ulcers often result from trauma, vascular insufficiency, neuropathy, leprosy, diabetes, malignancy or hemoglobinopathies 1 . If poorly managed these lesions may undergo malignant transformation 4-6 .
Thus, the study of non-healing skin ulcers is challenging and at times even frustrating than any other skin lesions. This study was taken keeping in view the present scenario were patient with non-healing ulcers go unnoticed for a long time without biopsy resulting in uncertainty of developing malignancy which can be identified at a very early stage by early histopathological examination.

Material And Methods:-
This study was hospital based two years prospective study extending from January 2016 to December 2017 conducted in Department of Pathology, Government Medical College Srinagar. During this period patients referred from peripheral hospitals with ulcers that had not healed for 4 weeks or more after conventional therapies were included in this study. The detailed history and clinical examination findings were retrieved from the case files. Biopsies received were processed as per the standard protocol and slides were examined by the senior pathologist in the department.

Results:-
During the two years period department received biopsies from 282 patients with non-healing ulcers. Out of 282 patients 180 were males and 102 were females with a M:F ratio of 1.76:1. 0ut of the 282 cases 100 (35.46%) were diagnosed as malignant ulcers and 182 (64.53%) were diagnosed as benign ulcers (Table 1). Out of the 282 cases, 70 cases (24.82%) were found to be neuropathic diabetic ulcers, 52 (18.43%) were diagnosed as tubercular ulcers, 44 (15.60%) as infectious, 4 (1.42%) as leprosy, 4 (1.42%) cases were due to parasitic infection (cutaneous leishmaniasis) and 8 cases (2.83%) as others. Benign ulcers were found to be fairly common below 50 years of age. Lupus Vulgaris was found to be the commonest form among the tubercular ulcers constituting 75% of the tubercular ulcers followed by Scrofuloderma accounting for 25% of the cases. Among malignant cases, that Squamous cell carcinoma is the most common variety of malignancy encountered in non-healing ulcer accounting for 82% of cases followed by Basal cell carcinoma 14% and malignant melanoma 4%.
Swabs from wound of 44 patients diagnosed as infectious ulcers were sent for culture and sensitivity tests, Staphylococcus was found to be the most common pathogen accounting for 50% of the bacteriological isolates. This was followed by klebsiella (16.67%), Proteus (16.67%) and Pseudomonas and Streptococcus was seen in 8.33% each. The group of "other ulcers' consist of venous ulcers which were diagnosed clinically and radiologically but no histopathological evidence could be found, ulcers due to foreign body granuloma histopathologically and ulcers for which no etiology could be identified histologically. Hence these ulcers could not be typified in definite etiological classes and were grouped together as others.

Discussion:-
Non healing ulcers are an important cause of morbidity in developing countries 7,8 . This may be explained by the poor socioeconomic conditions, poor health services in remote areas and lack of public awareness. In contrast with the developed countries, little is known about the prevalence and etiology of non-healing ulcers in these areas. One study from Nigeria reported that the most common etiologic factors were trauma, diabetes mellitus and sickle cell disease 9 Depending on the region, infectious causes such as cutaneous Leishmaniasis or Buruli ulcer may be encountered 10,11 .
In contrast venous ulcers are most common cause of ulcers in developed countries but are reported to be uncommon in tropical countries 12  In the present study, malignant ulcers were found to be the most common cause of non-healing ulcers of skin accounting for 35.46%. Of these squamous cell carcinoma is the most common 82% cases followed by Basal cell carcinoma (14%) and Malignant melanomas (4%). This finding is in concordance with that reported by Yakubu et al 15 . No venous or arterial ulcers were found histologically. However, two cases of venous ulcers were found which were diagnosed clinically and radiologically but no specific histologic features were identified to typify them, hence these were grouped under "other ulcers". Among the malignant ulcers Squamous cell carcinoma is the most common. Patients with non-healing ulcers for more than two years usually had malignant ulcers. Similar conclusions were drawn by Singh et al 16  patients presented with Marjolin's ulcer, and were confirmed histopathologically as Squamous cell carcinoma. This is in concordance with the conclusion drawn by Morra and colleagues 20 and Jellouli & colleagues 21 .
It was observed that common age group for malignant ulcer was 60-70 years followed by 50-60 years with a male preponderance. Similar conclusions were drawn by Singh et al 16 . Also malignancy below the age of 40 years was rare, only 4 cases were detected. This matches with that reported by Singh et al 16 who found 4 cases below the age of 30 years.
We observed neuropathic diabetic ulcers as the second common cause for non-healing ulcers, accounting for 24.82% of the non-healing ulcers. This is in accordance with studies by Neil et al 33 who found that approximately 20% of all non-healing ulcer related admissions in UK were due to diabetic foot ulcer disease. Alex and colleagues also reported an incidence rate that ranged from 8%-17%. The above studies are in contrast to the figures reported by Ch. Manes et al 34  The present study also observed two age peaks in presentation of the patients with non-healing ulcers due to diabetes. The first peak is in the 6 th decade accounting for 38.5% of the patients and the 2nd peak is in the 5 th decade accounting for 30.8% of the patients. The studies by Bansal et al 36  In the recent years, with the emergence of anti-Tubercular drug resistant strains and AIDS epidemic, there is a worldwide rise in the incidence of Tuberculosis. More so in the poverty struck areas of the world due to poor nutrition, poverty, non-availability of diagnostic aids and treatment, over-crowding, ignorance about the disease, rise in immunosuppressive therapy, decline in Tuberculosis control efforts and emergence of resistant strains of Mycobacterium tuberculosis have amplified the situation 25 However other studies by Gaur et al 37 reported Enterococcus as the most common organism and the study by Bansal et al 36 reported pseudomonas as the most common organism.
The reason for such discrepancy could not be assessed but may be due to the environmental factors and the intrinsic properties of the microorganism themselves as reported by Diana et al 42 and Mrek et al 43 . 1889
Thus it can be concluded from the study that non-healing of ulcers can be encountered at any age and etiology may vary from patient to patient, one geographical region to other and may also be different in different racial groups. Thus beside a good clinical diagnosis, early biopsy to rule out malignancy and identify the etiology is mandatory for a better outcome and minimize the morbidity and mortality among patients with non-healing ulcers.