Response to comments on 'Spontaneous regression of equine sarcoids is an exceptional event'.

Comments on 'Spontaneous regression of equine sarcoids is an exceptional event'.

Testicular germ cell tumors (TGCTs) are the most frequent type of cancer in young adults. An exceptional event is the spontaneous regression (SR) of the primary tumor. Herein, we describe a burned-out non-seminomatous TGCT case and relevant literature review. A 34-year-old male presenting with low back pain was found to have a retroperitoneal mass upon urotomography. During workup, a heterogeneous testicular mass was evident, and its biopsy showed findings that support the diagnosis of spontaneous tumoral regression. The patient underwent unilateral orchiectomy and a chemotherapy protocol was later initiated, with 85% regression of the retroperitoneal metastatic mass. No progression of the primary tumor has been found. The etiology of SR across different cancer types appears to be associated with the host’s immune response and an angiogenic disturbance of the tumor microenvironment. The burned-out phenomenon is a rare event that needs further research into its molecular sequencing.

Sarcoids are benign, yet locally aggressive skin tumours that commonly affect horses and other equid species. The lesions are induced by bovine papillomavirus types 1, 2, and probably 13 in conjunction with other factors including trauma and a genetic predisposition. Although sarcoids have a substantial impact on the health and welfare of affected equids, information on the immune response to bovine papillomavirus infection and resulting sarcoids is limited. However, there is evidence that sarcoid disease is associated with an impaired immune response to bovine papillomavirus infection. This observation agrees with the common perception of sarcoids as persistent lesions. Contrary to this general view, there are reports on the spontaneous regression of skin tumours diagnosed as sarcoids, giving rise to the question whether sarcoids can self-resolve, and if so, under which circumstances. This review addresses this unresolved issue.

We report the case of a 62-year-old man who presented with malignant lymphoma as recurrent multiple cranial nerve palsy after spontaneous regression of oculomotor nerve palsy. He developed ptosis and diplopia due to right oculomotor nerve palsy. Brain MRI/MRA showed no abnormality, and he recovered with conservative medical management. Three months later, he showed diplopia due to right abducens nerve palsy and facial pain and trigeminal sensory loss. Neurological examination revealed multiple cranial nerve palsy involved cranial nerve III, V, IX, and X of the right side. Serum soluble interleukin-2 receptor levels were normal, and cerebrospinal fluid examination was unremarkable. Steroid and subsequent intravenous immunoglobulin therapy didn't improve his symptoms. Six weeks after his admission, he showed rapid enlargement of the cervical lymph node and the right tonsil, and post-contrast T1-weighted MRI showed enlargement and enhancement of the left infraorbital nerve, the bilateral cavernous sinus, the bilateral facial nerves, and the left trigeminal nerve. The histopathologic examination of the tonsil biopsy revealed diffuse large B cell lymphoma. The cause of these symptoms was thought to be infiltrating the cavernous sinus, and adjacent nerves. Spontaneous regression of malignant lymphoma is an exceptional event, but this possibility should be considered so as to the correct diagnosis and proper treatment.

Spontaneous regression of cancer is an exceptional but well-documented biological event. Further understanding of this phenomenon and harnessing of the mechanisms involved will have significant preventative and therapeutic implications. In this review, the literature of spontaneous regression of colon or rectal cancer is reviewed from 1965 to 2005 to update reviews by Everson et al., Boyd and Challis et al. By adding to these, the author reports the entire series of colorectal cancer, which underwent documented spontaneous regression from 1900 to 2005. The demographic and pathologic characteristics, the details of regression and the outcome of reported cases are presented and discussed. Special emphasis is placed on identifying possible causes hypothesized by authors for occurrence of regression. Possible mechanisms operating to affect these regressions are also discussed.

ABSTRACTBackground: The progression of equine sarcoids (ES) is notoriously unpredictable. Making a choice for the appropriate treatment is challenging when dealing with milder manifestations of ES.Objective: The aim of this study was to investigate the clinical course of ES in young horses. Animals and methods: A cohort of 61 ES-affected three-year-old Franches-Montagnes horses and a breed-, age- and geographically matched control group of 75 ES-free peers were examined twice over a period of 5–7 years. Owners and caretakers were queried, using a standardized questionnaire.Results: More than half of the 38/61 (62%) horses that were ES-affected at the age of three, had become ES-free at the time of follow-up. In 29 of 38 horses, representing 48% of the entire study population, ES lesions had spontaneously disappeared without therapy. When differentiating the clinical types of ES lesions, occult ES underwent complete spontaneous regression in 65% (11/17), while verrucous lesions regressed spontaneously in 32% (9/28). None of the evaluated intrinsic or environmental factors showed a significant effect on the risk for development, regression or exacerbation of ES disease.Conclusions: Our results document a surprisingly high rate of spontaneous ES regression for young horses affected with milder manifestations of ES disease. These findings justify a ‘wait-and-see’ approach in selected cases of occult and verrucous ES, provided that all lesions are closely monitored. Furthermore, results of this study should also be considered when critically assessing treatment effects of therapies directed against ES, especially in the context of uncontrolled studies.

Resumo:Sarcoides são tumores fibroblásticos, considerados os tumores de pele mais comuns em pele de equinos e que raramente apresentam regressão espontânea. Papilomavírus bovino (BPV) tipos 1 e 2 são relacionados com a patogenia do sarcoide e, provavelmente, o BPV tipo 13 (BPV13), recentemente descrito, também pode estar associado com a formação dessa lesão. Neste estudo, 20 amostras de lesões cutâneas, sendo 12 constituídas por tecidos frescos e 8 amostras de tecido fixado em formalina e embebido em parafina, provenientes de 15 cavalos foram utilizadas para a identificação do DNA de BPV. A análise histopatológica (HE) confirmou todas as lesões como sarcoide. Para a amplificação do DNA de papilomavírus (PV) foram realizadas três reações de PCR. Como triagem, os primers IFNR2/IDNT2 foram utilizados para amplificar um fragmento da ORF L1 do PV. O segundo par de primersutilizado é complementar a sequência dos genes E5 e L2 de BPVs 1, 2 e 13. O terceiro par de primers(FAP59/FAP64) utilizado tem o gene L1 como alvo. A primeira e a segunda PCRs permitiram amplificar produtos em todas as amostras avaliadas. Entretanto, na terceira reação, na qual foram utilizados os primers FAP, foi possível amplificar produtos com tamanho molecular esperado somente nas amostras constituídas por tecidos frescos. O sequenciamento de nucleotídeos e as análises filogenéticas realizadas nos fragmentos E5L2 resultaram na identificação de BPV1, 2 e 13 em 14 (70%), 2 (10%) e em 4 (20%) amostras de sarcoides, respectivamente. As amostras de sarcoides de um dos animais continha somente o DNA de BPV1. Entretanto, nas amostras provenientes do segundo cavalo foi possível identificar o DNA de três tipos de Deltapapillomavirus bovino (BPV1, 2 e 13) em lesões distintas. Este estudo ratifica a presença do DNA de BPV1, 2 e 13 em lesões de sarcoides em equinos, além de identificar três tipos de BPVs em um mesmo animal e descrever pela primeira vez no Brasil a presença de BPV1 e 2 nesse tipo de lesão.