KIT and Melanoma: Biological Insights and Clinical Implications

Melanoma, originating from epidermal melanocytes, is a heterogeneous disease that has the highest mortality rate among all types of skin cancers. Numerous studies have revealed the cause of this cancer as related to various somatic driver mutations, including alterations in KIT—a proto-oncogene encoding for a transmembrane receptor tyrosine kinase. Although accounting for only 3% of all melanomas, mutations in c-KIT are mostly derived from acral, mucosal, and chronically sun-damaged melanomas. As an important factor for cell differentiation, proliferation, and survival, inhibition of c-KIT has been exploited for clinical trials in advanced melanoma. Here, apart from the molecular background of c-KIT and its cellular functions, we will review the wide distribution of alterations in KIT with a catalogue of more than 40 mutations reported in various articles and case studies. Additionally, we will summarize the association of KIT mutations with clinicopathologic features (age, sex, melanoma subtypes, anatomic location, etc.), and the differences of mutation rate among subgroups. Finally, several therapeutic trials of c-KIT inhibitors, including imatinib, dasatinib, nilotinib, and sunitinib, will be analyzed for their success rates and limitations in advanced melanoma treatment. These not only emphasize c-KIT as an attractive target for personalized melanoma therapy but also propose the requirement for additional investigational studies to develop novel therapeutic trials co-targeting c-KIT and other cytokines such as members of signaling pathways and immune systems.

Bone Necrosis in a Rheumatoid Arthritis Patient Secondary to Palatal Rotational Flap: A Practical Surgical Approach.

Aims: To present failed rotational palatal flap of a severe rheumatoid arthritis patient with a chronic oroantral fistula and a practical surgical method to deal with the systemic outcomes. Presentation of Case: Bone necrosis at donor site in closure of oroantral fistulas with palatal rotational flap is known to be very rare. We present a 57 years old female, rheumatoid arthritis patient under Methotrexate medication, with a chronic oroantral fistula in the left first molar region. Bone necrosis has been shown at the donor site after full thickness palatal rotational flap procedure. The treatment approach and alternative methods are discussed. Bone necrosis on the donor site has been treated with the re-rotation of the palatal rotational flap tissues, but this time with partial thickness to its original position. Successful healing has been achieved. Discussion and Conclusion: The result of this approach could help practitioners challenging with rheumatoid arthritis caused healing problems and oroantral fistulas.

What Lurks Beneath: Lacrimal Gland Adenocarcinoma Dedifferentiation to Sarcomatoid Carcinoma

This was a case of a young lady presenting with 10 year history of a mass in the right eye. It was found to be an adenocarcinoma of the lacrimal gland from histopathological biopsy. She underwent wide excision, orbital exenteration and reconstruction with a free rectus abdominis flap. Unfortunately, she had a tumour recurrence which was not controlled by radiotherapy and a second excision. The behavior of the tumour was aggressive, resulting in widespread metastases. She passed away within a year of her presentation. Of note, the histopathology report from the second excision turned out to be sarcomatoid carcinoma. This is described in the literature as dedifferentiation, or high grade transformation (HGT). Occurrence of dedifferentiation in salivary gland tumours is well-established, but not as well-described in lacrimal gland tumours. In this case, there was a severely delayed presentation of a lacrimal gland adenocarcinoma in a young person, which underwent dedifferentiation into a sarcomatoid carcinoma. This phenomena is associated with aggressive tumour biology behavior and poor prognosis, despite surgery and radiotherapy.

Episcleral plaque brachytherapy using ‘BARC I-125 Ocu-Prosta seeds’ in the treatment of intraocular tumors: A single-institution experience in India.

Context: To analyze the results of episcleral plaque brachytherapy using indigenous Bhabha Atomic Research Centre (BARC) Iodine-125 Ocu-Prosta seeds for the management of intraocular tumors from a single institute. AIM: To report our initial experience and learning curve on the use of ‘BARC I-125 Ocu-Prosta seeds’ for the management of intraocular tumors such as choroidal melanomas, retinoblastomas and vasoproliferative tumors (VPT). Materials and Methods: We retrospectively reviewed 13 eyes of 13 patients who underwent ophthalmic brachytherapy between May 2008 to March 2012. Nine cases had choroidal melanomas; three had retinoblastomas while one case had VPT. Results: For choroidal melanomas the average apical diameter before brachytherapy was 7.6 mm and average largest basal diameter was 12.1 mm, respectively, which reduced to 4.2 mm and 7.7 mm after the procedure at an average follow-up of 24 months (range 10-43 months). Retinoblastoma and VPT also showed good regression after brachytherapy. Conclusion: Plaque radiotherapy using 125I seeds can be performed under peribulbar anesthesia and provides a viable option for the management of intraocular cancer with minimal invasiveness and surgical complications. Patients in our studies experienced excellent local tumor control. With the availability of indigenous ‘BARC I-125 Ocu-Prosta seeds’ locally, cost effective ophthalmic brachytherapy can be performed in India.

Self-assessment of facial form oral function and psychosocial function before and after orthognathic surgery: a retrospective study.

Orthognathic surgery is a well-accepted treatment for patients with skeletal discrepancies. The primary motivation of many patients who seek orthognathic surgery is esthetics and not for correction of functional disability. The treatment is incomplete if the surgeon attempts to correct the physical deformity alone without adequate understanding and regard for the emotional framework. The purpose of this study is aimed at patient's self-perceptions of facial form oral function and psychosocial function before and after orthognathic surgery. Fifty patients were included in the study, of which 21 were used as control. Twenty-two questions were asked to evaluate the problem in all four areas as mentioned earlier. Each question takes a score from one to five. In group I, the internal consistency of each scale indicates moderate to high internal reliability, ranging from alpha = 0.71 for general health to alpha = 0.88 for psychosocial problem. In group II, except for functional problems, the internal consistency of each scale has moderate to high reliability. The psychological wellbeing of an orthognathic surgery patient is enhanced by careful preoperative counseling regarding the expected surgical treatment objectives, the operative course, and the expected postoperative sequelae. Patients who undergo orthognathic surgery readily accept the changes in their postoperative appearance and are satisfied with achieved results.

Acute lymphoblastic leukemia presenting as breast mass.

We present here a 34 years female who presented with bilateral breast lumps as the initial manifestation of acute lymphoblastic leukemia. She was treated with consolidation chemotherapy and showed good response.

Comparative study of visceral and parietal pleural biopsy in the etiological diagnosis of pleural diseases.

OBJECTIVE: The present study was planned to evaluate the efficacy and diagnostic reliability of conoctional parietal pleural biopsy to a technique of visceral pleural biopsy. METHOD: Study comprises of 54 diagnosed cases of pleural effusion and after establishing the clinical diagnosis for probable etiological causes. Then parietal pleural biopsy using absents punch biopsy needle and vesceral pleural biopsy using Prabhudesai et al technique was taken in all these patients. Size of the tissue yield; percentage of biopsies; diagnostic yield and sensitivity for these two techniques were compared. RESULTS: A definitive etiological diagnosis could be reached in 52 out of 54 patients on the basis of pleural biopsy (33 tuberculous, 16 malignant and 3 pyogenic), 23 (69.7%) tuberculous effusion patients were diagnosis by visceral pleural biopsy and 14 (42.4%) by parietal pleural biopsy out of 33 diagnosed tuberculous effusion cases. While for the 16 malignant effusions the visceral pleural biopsy showed suggestive histological change in 13 (81.25%) patients and the parietal pleural biopsy in seven (43.8%) with five (31.25%) of these patients being positive by both. All three pyogenic effusions showed only nonspecific inflammatory change in both pleurae. CONCLUSION: The mean size of biopsy sample obtained with modified Prabhudesai et al technique was significantly larger than that of the parietal pleural biopsy with Abrams punch (4.85 mm2 V/s 2.5 mm2 with P < 0.01). Adequate pleural tissue was identifiable in 94.4% and 90.7% of cases, respectively. The modified Prabhudesai et al technique proved to be effective safe and easily learnt. Visceral pleural sampling using this technique is a definite superior addition to the present diagnostic armamentarium of an idiopathic pleural effusion and its routine application together with parietal pleural biopsy will help to establish a definitive diagnosis in majority of patients with idiopathic pleural effusions.