Striking enhancement at the site of radiation for nivolumab-induced Stevens-Johnson syndrome.

Stevens-Johnson syndrome is a rare adverse cutaneous drug reaction characterized by epidermal detachment of <10% body surface area with an average mortality rate of 1-5%. The mechanism of SJS is not fully understood. Nivolumab is a monoclonal antibody directed against programmed cell death-1 protein (PD-1), a receptor with immune checkpoint inhibitory and antineoplastic activities. We present a case of SJS in a patient being treated with anti-PD-1 therapy nivolumab for metastatic squamous cell carcinoma of the oropharynx. This case is unusual because of the severe accentuation with striking enhancement at his prior radiation site and in the cutaneous region with heavier tumor burden from his metastatic disease. This reaction may give insight to the underlying pathophysiology of SJS, suggesting that immune checkpoint inhibitors can activate T-cells to target keratinocytes and that external factors may be involved in creating distinct epitopes for T-cell recognition. We hope this case adds to the body of knowledge in the pathogenesis of Stevens-Johnson syndrome and cutaneous adverse events seen with checkpoint inhibitors.

Propranolol and prednisolone combination for the treatment of segmental haemangioma in PHACES syndrome.

Posterior fossa malformations-haemangiomas-arterial anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical raphe syndrome (also known as PHACES syndrome) is a rare neurocutaneous disorder. Children presenting with these manifestations need careful ophthalmological, cardiac and neurological assessment. They may have one or more of these extracutaneous manifestations, the most common being cerebral and cardiovascular anomalies. There is controversy about treating these children with propranolol especially if they have cerebrovascular involvement with narrow, dysplastic or absent blood vessels. The concern with propranolol is that hypotension may lead to reduced cerebral blood flow and neurological consequences. Prior to propranolol the systemic treatment for haemangiomas was prednisolone and then the concern was the opposite, namely hypertension. Our proposal was whether a combination of these two drugs would provide a safer and faster recovery. We report three retrospective cases of PHACES syndrome, each of whom received treatment with a combination of propranolol and prednisolone: two children were started on prednisolone and propranolol was added because the haemangiomas failed to respond adequately; the third child was started on propranolol and developed peripheral ischaemia and ulceration necessitating a reduction in dose addition of a low dose of prednisolone. All three patients, who failed on the one treatment, responded well to combination therapy without any significant complications. These outcomes suggest that for some patients with PHACES syndrome the use of combination treatment with propranolol and prednisolone could be advantageous, potentially allowing for the introduction of low doses of each with an enhanced combined effect. The doses can be increased gradually depending on the magnetic resonance imaging findings.

Mycosis fungoides refractory to treatment - importance of a multidisciplinary approach.

We report a case of difficult-to-control mycosis fungoides (MF), where the role of the dental surgeon was crucial for the control and prognosis of the disease. A 62-year-old female patient diagnosed with MF had a previous record of red patches and small raised bumps on the face, along with a cancerous growth in the cervical and vulvar region. The patient was initially treated with methotrexate and local radiotherapy without resolution. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone was then started (CHOP protocol). The dental team of a reference hospital was consulted to evaluate swelling in the anterior region of the palate, which had been developing for two months, reporting discomfort when eating. The role of the dentistry team was fundamental in the differential diagnosis of oral lesions with dental infections, second neoplasia, or even a new site of disease manifestation, in addition to controlling mucosal changes resulting from chemotherapy. After ruling out dental infection, the dentistry team performed a lesion biopsy to confirm the diagnosis. The histopathological and immunohistochemical analysis showed atypical lymphoid infiltration of T cells (CD3+/CD4+/CD7-/CD8-), coexpression of CD25, and presence of CD30 cells, corresponding to the finding for MF. Identifying CD30 + allowed for a new chemotherapy protocol with brentuximab vedotin (BV) combined with gemcitabine. This protocol effectively controlled MF, which previous protocols had failed to do. The diagnosis by the dental team was essential for therapeutic change and improvement of the patient's clinical condition without the need for invasive medical procedures.

Synchronous squamous cell carcinoma and chronic lymphocytic leukemia of the palate.

Although multiple synchronous malignancies of the same histological type have been described frequently in the upper aerodigestive tract, this is a less frequent phenomenon when dealing with tumors of different lineage. We present a case of a man who developed simultaneously an oral squamous cell carcinoma and chronic lymphocytic lymphoma of the palate without any previous risk factors. To the best of our knowledge, this is the first case well documented in the literature of synchronous oral squamous cell carcinoma and chronic lymphocytic lymphoma of the palate in the same sample. The presence of multiple primary malignancies of different histological types not only complicates the treatment but also worsens the prognosis of the patient.

Granulocytic sarcoma of palate. Case report and review of literature.

A rare case of granulocytic sarcoma of the hand and palate, also known as chloroma, occurring in an adolescent patient is presented. Diagnostic clinical criteria, along with treatment pictures, are also reviewed.

Carcinoma ex pleomorphic adenoma of soft palate with cavernous sinus invasion.

BACKGROUND: Carcinoma ex pleomorphic adenoma (CXPA) is an aggressive salivary gland malignancy and rare in minor salivary gland. A soft palate CXPA initially presenting as direct cavernous sinus (CS) invasion is very rare. CASE PRESENTATION: A 60-year-old male had a 3-month history of a small soft palatal mass with progressing left cheek numbness, proptosis, and disturbed vision. Biopsy of soft palatal tumor showed pleomorphic adenoma. Magnetic resonance imaging showed a tumor involving left maxilla, and extended from pterygopalatine fossa, inferior orbital fissure to CS. Excision of tumor revealed CXPA. Adjuvant concomitant chemo-radiation therapy (CCRT) was given. The tumor recurred 5 months later in left CS which was re-treated with CCRT. The disease status was stable at 2 years after the diagnosis of CXPA. CONCLUSION: We present this case to emphasize that patients with symptoms such as facial numbness, proptosis and disturbed vision should be carefully investigated for lesions invading CS by perineural spread.

The use of pedicled temporal musculoperiosteal flap with or without free calvarial bone graft in maxillary reconstructions.

Various techniques have been used to repair maxillary defects. The aim of this study was to evaluate the suitability of pedicled temporal musculoperiosteal flap (PTMF) and free calvarial bone graft for the reconstruction of maxillary defects. In this retrospective series, 34 patients operated on from 1995 to 2006 at Turku University Central Hospital because of defects of maxilla reconstructed using PTMF with or without free calvarial bone graft were evaluated. The diagnosis, the indication for surgery, the location and staging of the tumours, and the type of radiotherapy used were reviewed. The classification of the maxillary defects was performed according to the classification of Brown (Br J Oral Maxillofac Surg 40:183-190, 2002) and the success rates of the reconstructions were evaluated. Of the patients, 32 had been operated on due to a malignant tumour, one due to a benign tumour and one due to posttraumatic palatal defect. Preoperative radiotherapy (n = 14), preoperative chemoradiotherapy (n = 2) or postoperative radiotherapy (n = 11) had been used in the tumour group. As a reconstructive method, PTMF had been used with (n = 21) or without (n = 13) free calvarial bone graft. The use of free calvarial bone graft did not have a significant effect on flap survival. At 1-month follow-up, the flap survival in the 32 patients was 71.9%, whereas 28.1% of the patients suffered from partial flap loss, but there was no total flap loss. At 6-month follow-up, the flap survival in 26 patients was 76.9%, whereas 7.7% of the patients suffered from partial flap loss, and there were four (15.4%) total flap losses. If unilateral alveolar maxillectomy had been performed (Brown classification a), at 1-month follow-up, the flap survival was 82.6%, 17.4% of the patients suffered from partial flap loss, and there was no total flap loss. At 6-month follow-up, the flap survival was 89.5%, while 10.5% of the patients suffered from partial flap loss, and there was no total flap loss. The application of PTMF with or without free calvarial bone graft for reconstruction of limited palatal and maxillary defects appears to be feasible.

Acute hearing loss, dysarthria, dysphagia, and a rubbery intraoral mass in an 18-year-old woman.

Rhabdomyosarcoma is the most common soft tissue tumor of childhood, frequently presenting in the head and neck, genitourinary tract, or extremities. We present a case of rhabdomyosarcoma in which an 18-year-old woman presented with abrupt onset unilateral hearing loss, tinnitus, dysarthria, dysphagia, and a new painless red bump on the palate. With an alveolar subtype and older age, both predictors of poor prognosis, early recognition of disease of these symptoms is vital.

Disseminated Kaposi's sarcoma and HCV infection: only a casual relationship? A case report.

The authors present a case of disseminated Kaposi's sarcoma in a male patient, HIV negative and Hepatitis C virus (HCV) positive. Although it is well-known that in HCV positive patients the onset of cutaneous diseases such as porphyria cutanea tarda, mixed essential cryoglobulinemia, lichen planus, polyarteritis nodosa, itch/prurigo, is possible, papers on its association with disseminated Kaposi's sarcoma in HIV negative patients are rare in the literature. Such an association is probably not a matter of chance: in fact, the changes to the immune system induced by the HCV virus, in synergy with those induced by the Human Herpetic virus-8, could likewise play a role in the development of Kaposi's sarcoma as happens in patients with immunodeficiency .

Human immunodeficiency virus-associated Kaposi sarcoma as an immune reconstitution inflammatory syndrome: a literature review and case report.

BACKGROUND: Kaposi sarcoma (KS) is the most common human immunodeficiency virus (HIV)-associated neoplasm (HIV-KS). Highly active antiretroviral therapy (HAART) results in a decrease in the incidence and prevalence of HIV-KS as well as in clinical improvement. However, in a subset of subjects who are HIV seropositive, KS may recrudesce early following the introduction of HAART as an immune reconstitution inflammatory syndrome (IRIS). METHODS: The management of a patient who is HIV seropositive with rapid clinical worsening of oral KS lesions shortly after the initiation of HAART was documented. Repeated serologic testing for CD4(+) T-cell count and microscopic examination of two biopsy specimens of the oral lesion, one taken before and the other taken after cytotoxic chemotherapy, followed by surgical excision was the treatment modality used. RESULTS: Microscopic examination of the incisional biopsy specimen taken from the oral lesion at the time of the initial consultation confirmed the clinical diagnosis of KS. The sequential serological tests showed a progressive increase in CD4(+) T-cell counts that paralleled the rapid clinical worsening of the KS disease. This was consistent with the diagnosis of IRIS-associated HIV-KS. Subsequent cytotoxic chemotherapy brought about resolution of the IRIS and regression of the HIV-KS lesions. Microscopic examination of a biopsy specimen obtained after cytotoxic chemotherapy did not show any of the original KS. The residual palatal exophytic mass was excised. CONCLUSIONS: IRIS-associated HIV-KS is not a disease, but rather a temporary paradoxical immunoinflammatory reaction brought about by improvement in immune status following HAART. IRIS-associated HIV-KS can be controlled effectively by limited systemic cytotoxic chemotherapy in the setting of HAART.

Kindler syndrome complicated by invasive squamous cell carcinoma of the palate.

INTRODUCTION: Kindler syndrome is a very rare, autosomal recessive genodermatosis characterized by skin fragility and photosensitivity in infancy with progressive poikiloderma. CASE REPORT: We report the case of a young woman with a history of Kindler syndrome predominantly characterized by extensive involvement of the oropharyngeal mucosa. The patient presented with an ulcerative lesion of the palate. Computed tomography and biopsy concluded on unresectable invasive squamous cell carcinoma of the hard palate. Neoadjuvant chemotherapy was proposed, but the patient died after the first course of chemotherapy in a context of severe gastrointestinal mucositis and generalized sepsis. DISCUSSION: Mucosal manifestations of Kindler syndrome have been described in the literature, but very few cases of malignant transformation to squamous cell carcinoma have been reported, although it is a very well known, long-term complication of this disease. To our knowledge, this is the second reported case of Kindler syndrome complicated by invasive squamous cell carcinoma of the hard palate.

Gingival involvement in a case series of patients with acquired immunodeficiency syndrome-related Kaposi sarcoma.

BACKGROUND: This case series presents the polymorphic clinical characteristics of gingival acquired immunodeficieny syndrome (AIDS)-related Kaposi sarcoma (KS), a malignancy that is gradually becoming uncommon in developed nations. An up-to-date overview of the related epidemiology, etiopathogenesis, histopathology, and treatment is provided, along with a pictorial guide to ease clinical diagnosis. METHODS: The oral/maxillofacial pathology records at Aristotle University and the University of Geneva were retrospectively reviewed. Thirty-two cases diagnosed with oral AIDS-related KS were retrieved between 1991 and 2004. KS diagnosis was established histologically by incisional biopsies from intraoral lesions. All charts contained clinical oral examination data, radiological images, and detailed photographic records. RESULTS: Thirteen patients (12 males and one female) presented with KS gingival involvement (40.6%). Eleven of the male patients were homosexual/bisexual men. The mean age of the patients at the time of intraoral KS diagnosis was 42.1 years, and the mean CD4 cell count was 103 (0 to 481). Gingival epidemic KS presented with various degrees of pigmentation and a wide range of clinical patterns, from relatively flat macules (early stage) to tumors with variable nodular morphology (advanced disease). Solitary or multiple gingival involvement may appear concomitantly with palatal and/or cutaneous lesions. CONCLUSIONS: Even though the incidence of intraoral KS had fallen precipitously in developed countries after the mid-1990s, gingival KS should be considered in the differential diagnosis of every pigmented gingival lesion. Periodontists are in a unique position to identify gingival involvement of intraoral KS and facilitate early diagnosis.

A case of double cancer involving oral malignant melanoma and gastrointestinal stromal tumor (GIST).

We report a very rare case of double cancer involving palatal malignant melanoma and gastrointestinal stromal tumor (GIST), a rare tumor of the gastrointestinal tract originating from a primitive mesenchymal cell. After chemotherapy, radiation therapy, and treatment with interferon and OK-432, the GIST was resected and the melanoma disappeared. The patient has had no evidence of recurrent tumor, and the patient's clinical course has been uneventful for 1 year. This is probably the first report of synchronous double cancer involving oral malignant melanoma and GIST.

Regression of AIDS-related Kaposi's sarcoma following ritonavir therapy.

This paper describes a case report of an HIV-infected patient with mucocutaneous Kaposi's sarcoma (KS) with oral involvement, which presented complete clinical resolution of lesions on antiretroviral treatment with ritonavir, an HIV-1 protease inhibitor. Although it has still not been demonstrated that ritonavir has a specific antiviral action against HHV-8, a gamma herpesvirus probably involved in KS aetiopathogenesis, it has been proven that it reduces the HIV load significantly. This affects certain growth factors of KS, such as Tat protein and cytokines, and favours recovery of immune function, which correlates with protection against AIDS-defining conditions.

Lethal cardiac toxicity after cisplatin and 5-fluorouracil chemotherapy. Report of a case with necropsy study.

This article presents a patient affected with epidermoid carcinoma of the soft palate who developed a dilated myocardiopathy with aortic embolism and fatal left cardiac failure after treatment with cisplatin (100 mg/m2, day 1) and 5-fluorouracil (1 g/m2/day i.v. days 2-6). The postmortem necropsy study showed diffuse interstitial edema and intracytoplasmic vacuolization of myocytes, without inflammatory changes. These findings were interpreted as acute toxic myocardiopathy, probably due to 5-fluorouracil treatment. Although the patient also received cisplatin, metoclopramide, allopurinol, thiethylperazine, and amitriptyline, before the onset of clinical symptoms, these drugs were not considered to play an important role in the production of this cardiopathy because of the dosage, necropsy findings, and lack of previous report.

Oral mucosal melanoma: a series of case reports.

INTRODUCTION: Due to the rarity of oral malignant melanomas case reports are a necessary source of information. Ten new cases are reported with a minimum follow-up of 3 years. PATIENTS AND METHODS: Patients were treated during a period of 10 years. Clinical, demographic and pathologic findings were examined. RESULTS: In 6 males (60%) and 4 females with a mean age of 64.3 years the tumour locations were: hard palate-maxillary gingiva (3 cases), maxillary gingiva (2), lower gingiva (2), tongue (2), hard/soft palate-buccal mucosa (1). Pre-existing melanotic pigmentation had been present in 4 patients. Four patients were in stage I, 5 in stage II, and 1 in stage III. Surgical excision was the primary treatment in 9 cases. Five patients underwent simultaneous neck dissections. All patients received radiation and multimode adjuvant therapies. After a 3-year follow-up 3 patients are still alive (50% (2/4) of those presenting in stage I and 20% (1/5) in stage II). CONCLUSIONS: Due to the rarity of oral melanoma, individual experience is limited. The poor prognosis and the different treatments reflect this situation.

Photofrin-mediated photodynamic therapy of chemically-induced premalignant lesions and squamous cell carcinoma of the palatal mucosa in rats.

Photodynamic therapy (PDT), an experimental cancer therapy, was studied in an animal model of chemically-induced epithelial dysplasia and squamous cell carcinoma. PDT was performed 24 hours after i.v. injection of 2.5 mg/kg bw Photofrin, and using 100 J/cm2 incident light at two activation wavelengths (514.5 nm or 625 nm). Two days after PDT, the majority of rats macroscopically showed a marked erythema of the entire palatal region. Microscopically all the rats showed oedema, haemorrhage, and necrosis of the epithelium of the intermolar area. The long-term results were not so favourable. No evidence of disease was found in 6 out of 20 rats in the 514.5 nm group and in 2 out of 20 rats in the 625 nm treated group. Epithelial dysplasia was found in 14 out of 20 rats in the 514.5 nm group, and in 18 out of 20 rats of the 625 nm treated group. Squamous cell carcinomas were found in 4 out of 20 rats treated with 514.5 nm and in 7 out of 20 rats in the 625 nm treated groups. Comparing both treatment wavelengths, better results were obtained in the 514.5 nm groups as this wavelength gave less normal tissue damage. Based on the results of this study the application of PDT for the treatment of field cancerization and squamous cell carcinoma of the oral cavity, is discussed.