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The Inca child Mummy (1480-1650 AD): (a) frontal view of the bundle showing a false decorated head. (b) In an axial
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The earliest examples of neurofibromatosis (in this case type 1, NF1) can be traced in the Ebers Papyrus (Ancient Egypt, 1.500 B.C.), in a Hellenistic statuette (Smyrna, 323 B.C.), in the coinage of the Parthians kings (247 B.C.) and in some 13th century monks' drawings. These earlier examples are somewhat less well defined as compared to the most...
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Context 1
... Almanac de Paris from 1833- which gives a list of all professionals working in the city-names a sculptor "Trajin" as living in Saint Germain-des-Pres, where Hugo also lived at the time he published the novel at age 29 years; since that time Hugo had lived only in Paris (Cox, 1985). (Figure 9a), belonged to a 7-to 9-year-old boy, was investigated ( Panzer et al., 2017) using multi-slice CT with slice thickness standardized for assessment of soft tissue preservation, and revealed indicators of: (a) NF1 (Figure 9b-d) [multiple lobulated masses suggestive of para- vertebral neurofibromas in the neck, at the cervico-thoracic junction and in the lumbar spine; a plexiform mass within the right sacral plexus (Caprotti, 1980;Simili, 2001;Tega, 2002). He is usually referred to, especially in older literature, as Aldrovandus; his name in Italian is equally given as Aldroandi (Olmi, Tugnoli Pattaro, Tosi, & Beretta, 2016). ...
Context 2
... Almanac de Paris from 1833- which gives a list of all professionals working in the city-names a sculptor "Trajin" as living in Saint Germain-des-Pres, where Hugo also lived at the time he published the novel at age 29 years; since that time Hugo had lived only in Paris (Cox, 1985). (Figure 9a), belonged to a 7-to 9-year-old boy, was investigated ( Panzer et al., 2017) using multi-slice CT with slice thickness standardized for assessment of soft tissue preservation, and revealed indicators of: (a) NF1 (Figure 9b-d) [multiple lobulated masses suggestive of para- vertebral neurofibromas in the neck, at the cervico-thoracic junction and in the lumbar spine; a plexiform mass within the right sacral plexus (Caprotti, 1980;Simili, 2001;Tega, 2002). He is usually referred to, especially in older literature, as Aldrovandus; his name in Italian is equally given as Aldroandi (Olmi, Tugnoli Pattaro, Tosi, & Beretta, 2016). ...
Context 3
... was through the examination of 47-year-old Michel Bur ( Figure 19b) that von Recklinghausen confirmed his suspicions (Warkany, 1981;Wilkins & Brody, 1971). With a live patient, von Recklinghausen was able to probe tumors of the peripheral nerves, distinguishing them from fibromas as the skin covering them could be moved. ...
Citations
... 3 Neurofibromatosis type 2 was first described by Scottish surgeon J H Wishart in 1822. 4 While neurofibromatosis type 1 is caused by a defect in tumour suppressor gene neurofibromin which is located on the long arm of chromosome 17 (17q11.2), neurofibromatosis type 2 is caused by a mutation in tumour suppressor gene merlin located on the long arm of chromosome 22 (22q12.2). 1 Merlin protein is responsible to maintain cellto-cell connections of cytoskeleton with the plasma membrane, thereby regulating the shape and motility of the cell. 1 Neurofibromatosis type 2 is characterised by the development of multiple neoplasms in the central and peripheral nervous system with variable clinical course. ...
... In addition to this, the stylistic "furrowing of the brows, parting of the lips, and placing a groove on either side of the mouth" and occasional protruding ears displayed on the coins suggest a high likelihood of realism in the depiction of the kings [12]. These nodules clearly "represented … an important (distinctive) facial feature" that may have also helped strengthen the legitimacy of the dynasty's reign [14]. ...
Multiple kings of the Arsacid Dynasty of the ancient Parthian Empire are depicted on their coinage with a recurrent facial lesion, one that is found across multiple generations. Multiple theories have attempted to explain this phenomenon, from basal cell carcinoma to hereditary trichoepithelioma. In this paper, we suggest that these lesions are possibly a representation of the neurofibromas found in Neurofibromatosis 1, an autosomal dominant disease process.
... However, many of these tumors are unfortunately only diagnosed at an advanced stage, where they have metastasized to distant sites in the body or are otherwise unresectable. 2 Alternative treatment strategies are similar to those employed for other soft tissue sarcomas, involving a combination of first-line anthracycline-based drugs and cytotoxic therapies such as the alkylating agent ifosfamide and the topoisomerase II inhibitor etoposide. 3 However, these therapeutic regimens tend to have limited efficacy as MPNSTs are generally insensitive to conventional chemotherapy drugs. ...
Immune-based therapies represent a new paradigm in the treatment of multiple cancers, where they have helped achieve durable and safe clinical responses in a growing subset of patients. While a wealth of information is available concerning the use of these agents in treating the more common malignancies, little has been reported about the use of immunotherapies against malignant peripheral nerve sheath tumors (MPNSTs), a rare form of soft tissue sarcoma that arises from the myelin sheaths that protect peripheral nerves. Surgical resection has been the mainstay of therapy in MPNSTs, but the recurrence rate is as high as 65%, and chemotherapy is generally ineffective. The immune contexture of MPNSTs, replete with macrophages and a varying degree of T cell infiltration, presents multiple opportunities to design meaningful therapeutic interventions. While preliminary results with macrophage-targeting strategies and oncolytic viruses are promising, identifying the subset of patients that respond to immune-based strategies will be a milestone. As part of our effort to help advance the use of immunotherapy for MPNSTs, here we describe recent insights regarding the immune contexture of MPNSTs, discuss emerging immune-based strategies, and provide a brief overview of potential biomarkers of response.
... The reports about the sex predilection were controversy; Some reported that there was no sex predilection [5], while others reported male predominance [6]. Schwannomas are usually solitary, however multiple lesions may also be seen in neurofibromatosis type 1 or type 2 [7]. ...
... The reports about the sex predilection were controversy; Some reported that there was no sex predilection [5], while others reported male predominance [6]. Schwannomas are usually solitary, however multiple lesions may also be seen in neurofibromatosis type 1 or type 2 [7]. ...
Background: Schwannoma is a benign tumor arises from Schwann cells of the peripheral nerves. Tongue base schwannomas are very rare and have been sporadically reported; it is usually missed when evaluating a tongue base mass. This work aimed to report a new case of tongue base schwannoma and to review the literature about this tumor. Case presentation: A male patient of 40 years old presented with slowly enlarging mass at the tongue base. Clinical and radiological findings highly suspected of tongue base benign lesion. Trans-oral resection was done and the specimen was subjected to the histopathological evaluation. Conclusion: Schwannoma should be considered for a well-defined, painless, firm swelling at the tongue base.
... The first scientific description of the disease was published by Dr. Mark Akenside. A German pathologist, Dr. Friedrich von Recklinghausen actually coined the name of the disease and was acknowledged as the one who discovered it later in 1882 [2,3]. Dr. Von Recklinghausen characterized the disease by a phenomenon of light brown spots on the skin that 2 DOI: 10 Figure 2: Skin presentation of the patient's mother. ...
A 20-year-old female patient with no past medical history and no medication use, presented to our clinic complaining of "non-specific lower back pain". Upon examining her back, multiple hyperpigmented cafe-au-lait spots with some pedunculated lesions were noted. The patient stated that she was born with multiple abnormal skin lesions all over her body. She is a non-smoker without any organic symptomatology. The patient denied shortness of breath, chest pain, or abdominal pain at this time. Her mother, a 58-year-old female who accompanied the patient, also stated that she has a similar skin presentation. Physical Examination Vital signs: blood pressure, 118/75 mm Hg; pulse, 76 beats/ min; respiratory rate, 16 breaths/min; height, 162.5 cm; weight, 52.7 kg; temperature, 37.9°C; and oxygen saturation, 98% on room air. During examinations of both eyes, the patient had multiple hypo-pigmented elevated lesions in her iris suggestive of Lisch nodules. Her visual acuity was 20/20 in both eyes. Examination of the face showed no visible craniofacial abnormalities (Figures 1 and 2 both of them provided verbal consent for using the figures). She had an oral neurofibroma with mild gingival hyperplasia and multiple dental caries in her molars. Dermatological examination showed multiple non-painful cutaneous lesions with smooth bordered café-au-lait macules on her back and lower extremities. She also presented with an elevated hairy rubber-like pigmented lesion suggesting a plexiform neurofibroma in her right lumbar and abdominal region. The patient had inguinal and axillary freckling consistent with Crowe sign. The patient's mother had similar skin neurofibromas which we were able to compare with patient's presentation during the examination. The patient had no dys-pnea, no evidence of cyanosis, and no neurological focal signs. Furthermore, the patient's mother does not complain of any neurological symptoms. For our patient, due to non-specific back pain, she was advised to have an MRI of the lower lum-bar region and anti-inflammatory medication was prescribed to address the pain.
... 3 Neurofibromatosis type 2 was first described by Scottish surgeon J H Wishart in 1822. 4 While neurofibromatosis type 1 is caused by a defect in tumour suppressor gene neurofibromin which is located on the long arm of chromosome 17 (17q11.2), neurofibromatosis type 2 is caused by a mutation in tumour suppressor gene merlin located on the long arm of chromosome 22 (22q12.2). 1 Merlin protein is responsible to maintain cellto-cell connections of cytoskeleton with the plasma membrane, thereby regulating the shape and motility of the cell. 1 Neurofibromatosis type 2 is characterised by the development of multiple neoplasms in the central and peripheral nervous system with variable clinical course. ...
Sir, Neurofibromatosis type 2 is a rarely seen clinical syndrome compared to neurofibromatosis type 1. 1 Based on severity as well as clinical course, neurofibromatosis type 2 is classified into two types: the less aggressive late onset Feiling-Gardner phenotype with single tumour in the central nervous system and the aggressive Wishart phenotype in young adults with multiple tumours in central as well as the peripheral nervous system. 2 We report a case of a 20-year-old man suffering from the aggressive Wishart phenotype. A 20-year-old man presented with complaints of multiple painless skin-coloured swellings on the body over seven years and progressive hearing loss of left ear, hoarseness of voice, weakness as well as deformity of the right hand of six months duration. None of his family members had similar illness. Neurological examination revealed left-sided lower motor neuron type of facial palsy and contralateral hemiparesis [Figure 1a]. Right paralytic claw hand with hypothenar atrophy was noticed [Figure 1b]. Dermatological examination revealed nodules on the scalp, cheek, back and right upper limb [Figures 1c and d]. Fundoscopy showed bilateral optic disc edema with pericapillary hemorrhages [Figures 2a, b]. The audiogram showed bilateral sensorineural deafness (left > right) while indirect laryngoscopy revealed left vocal cord palsy. Axial contrast-enhanced T1 magnetic resonance imaging of the brain showed bilaterally enhancing vestibular schwannomas (right greater than left) [Figures 3a and b] and ependymomas in bilateral lateral ventricles [Figure 3c]. Sagittal contrast-enhanced T1 images revealed extra-axial lesion from C1 to C3 level with extension into neural A rare case of aggressive phenotype (Wishart) of neurofibromatosis type 2 How to cite this article: Das P, Singh GK, Gowda P, Barui S, Das DS, Kushwaha S, et al. A rare case of aggressive phenotype (Wishart) of neurofibromatosis type 2. Indian J Dermatol Venereol Leprol Sir, Neurofibromatosis type 2 is a rarely seen clinical syndrome compared to neurofibromatosis type 1. 1 Based on severity as well as clinical course, neurofibromatosis type 2 is classified into two types: the less aggressive late onset Feiling-Gardner phenotype with single tumour in the central nervous system and the aggressive Wishart phenotype in young adults with multiple tumours in central as well as the peripheral nervous system. 2 We report a case of a 20-year-old man suffering from the aggressive Wishart phenotype. A 20-year-old man presented with complaints of multiple painless skin-coloured swellings on the body over seven years and progressive hearing loss of left ear, hoarseness of voice, weakness as well as deformity of the right hand of six months duration. None of his family members had similar illness. Neurological examination revealed left-sided lower motor neuron type of facial palsy and contralateral hemiparesis [Figure 1a]. Right paralytic claw hand with hypothenar atrophy was noticed [Figure 1b]. Dermatological examination revealed nodules on the scalp, cheek, back and right upper limb [Figures 1c and d]. Fundoscopy showed bilateral optic disc edema with pericapillary hemorrhages [Figures 2a, b]. The audiogram showed bilateral sensorineural deafness (left > right) while indirect laryngoscopy revealed left vocal cord palsy. Axial contrast-enhanced T1 magnetic resonance imaging of the brain showed bilaterally enhancing vestibular schwannomas (right greater than left) [Figures 3a and b] and ependymomas in bilateral lateral ventricles [Figure 3c]. Sagittal contrast-enhanced T1 images revealed extra-axial lesion from C1 to C3 level with extension into neural A rare case of aggressive phenotype (Wishart) of neurofibromatosis type 2 How to cite this article: Das P, Singh GK, Gowda P, Barui S, Das DS, Kushwaha S, et al. A rare case of aggressive phenotype (Wishart) of neurofibromatosis type 2. Indian J Dermatol Venereol Leprol
... Although several researchers have made remarkable contributions to the understanding of this disease, Von Recklinghausen is credited with discovering the pathogenesis of these tumors. The nature of the neoplastic tissue in both types of tumor was described to be almost identical and result from the mingling of neural elements and connective tissue cells, thus giving birth to the term 'neurofibroma' [1][2][3]. ...
The first description of histopathological variants of neurofibroma dates back to 1994. Over the years, many individual case reports elucidating unusual histologic features in neurofibroma have been added to the literature, some of which have defined criteria, with the others falling under the roof of benign neural neoplasms. These unusual features, which sometimes may lead to pauses in identifying a common benign tumor such as neurofibroma. Awareness of these variants may help dermatopathologists avoid misinterpretation. Thus, this review aims to summarize all novel and unusual histopathological variants of cutaneous neurofibroma reported to date, in addition to any unusual variants that we encountered in our practice.
... e term neurofibromatosis (NF) was first introduced to the medical literature by Frederick von Recklinghausen in 1882 to characterize the structural relation and mutual involvement of neuromas and fibromas. [20,100] NF Type 1 (NF1) and Type 2 (NF2) are both dominantly inherited; nonetheless, they are distinct disease entities. [53,85] NF1 is caused by a mutated tumor suppressor gene on the long arm of chromosome 17 (17q11.2). [8,117] e disorder is most commonly defined by the cutaneous stigmata, café-au-lait spots, and neurofibromas. ...
Background: Neurofibromatosis (NF) is an umbrella term that refers to three distinct disease entities: NF Type 1, Type 2, and schwannomatosis. Here, we reviewed the scientific performance and the most influential publications on NF.
Methods: A keyword-based search was performed using the Scopus database. e top 100 articles were grouped based on NF types and the studied entities. e differences between the articles, authors, and journals were quantified based on certain parameters. Other parameters were collected for the complete citational analysis.
Results: Thee top 100 articles were published between 1961 and 2020. e most trending period of research was in the 1990s and articles studying the clinical aspect and the underlying genetic correlation made up 84% of all articles from the list. The United States of America (USA) had the highest number of contributions (69 articles, 69%). The top institute of contribution to the list was the Howard Hughes Medical Institute, USA (14 articles, 14%). Author-based analysis reveals that the neurologist D. H. Gutmann from St. Louis Children’s Hospital, USA, was the most active and authored 11 articles (11%) on the list.
Conclusion: The publication trends show that articles studying medical and surgical management were of little interest. e top 100 articles did not include any randomized control trials, and the highest level of evidence was obtained from reviews of pooled knowledge as well as population-based and longitudinal studies.
... Neurofibromas are benign peripheral nerve sheath tumors mainly composed of neoplastic cells showing schwannian differentiation admixed to a minor component of cells with fibroblastic and perineurial differentiation. They represent the most common peripheral nerve sheath tumors and are usually diagnosed as apparently sporadic lesions; however, there is increasing evidence that a large number of histologically proven neurofibromas arise within the context of classical neurofibromatosis type 1 (NF1) or its alternative forms ( Table 2), and that, when isolated, they may be caused by mosaic phenomena occurred in the NF1 gene at a somatic level, and it is currently accepted that virtually all individuals affected by NF1 develop neurofibromas (Figures 1 and 2) [8]. Based on the recently revised criteria for NF1 [2] and a newly proposed classification of the different forms of neurofibromatosis and schwannomatoses [9][10][11] (Table 2), a surgical pathologist should be aware of the possibility of this spectrum of disorders when he/she is dealing with an isolated neurofibroma, with multiple lesions or a plexiform neurofibroma from an individual without a personal or familial history of classical NF1 (Table 2); similarly, the chance of being affected by classical NF1 is likely when dealing with the above-mentioned tumors arising in a child with an affected parent by NF1. ...
... Schwannoma is an encapsulated benign nerve sheath tumor arising from small or large nerves that is composed almost exclusively of spindled cells showing the morphological, immunohistochemical, and ultrastructural features of Schwann cells [1,4]. Although most cases (90% of cases) arise as isolated/solitary lesions ( Figures 10 and 11), their occurrence within the context of NF2-related-schwannomatosis or NF2/MERLIN schwannoma predisposing syndrome (formerly, NF2), SMARCB1/LZTR1-related-schwanomatoses or SMARCB1/LZTR1 schwannoma predisposing syndromes (formerly, schwannomatosis) and 22q-related-schwannomatosis or 22q schwannoma predisposing syndrome (Table 7) is well-known [1,8]. Recently, the umbrella term "schwannomatosis" has been proposed to encompass the spectrum of syndromes characterized by the development of (or the predisposition to develop) schwannomas, [as opposed to the spectrum of syndromes characterised by the development of (or predisposition to develop) neurofibromas: i.e., NF1 and related disorders], including NF2 (now called NF2-related-schwannomatosis or NF2/MERLIN schwannoma predisposing syndrome) and schwannomatosis (now called SMARCB1-related and LZTR1-related-schwannomatoses or SMARCB1/LZTR1 schwannoma predisposing syndromes) ( Table 7) [3]. ...
Peripheral nerve sheath tumors encompass a wide spectrum of lesions with different biological behavior, including both benign and malignant neoplasms as well as the recent diagnostic category, i.e., “atypical neurofibromatous neoplasm with uncertain biologic potential” to be used only for NF1 patients. Neurofibromas and schwannomas are benign Schwann-cell-derived peripheral nerve sheath tumors arising as isolated lesions or within the context of classical neurofibromatosis or schwannomatoses. Multiple tumors are a hallmark of neurofibromatosis type 1(NF1) and related forms, NF2-related-schwannomatosis (formerly NF2) or SMARCB1/LZTR1-related schwannomatoses. Perineuriomas are benign, mostly sporadic, peripheral nerve sheath tumors that show morphological, immunohistochemical, and ultrastructural features reminiscent of perineurial differentiation. Hybrid tumors exist, with the most common lesions represented by a variable mixture of neurofibromas, schwannomas, and perineuriomas. Conversely, malignant peripheral nerve sheath tumors are soft tissue sarcomas that may arise from a peripheral nerve or a pre-existing neurofibroma, and in about 50% of cases, these tumors are associated with NF1. The present review emphasizes the main clinicopathologic features of each pathological entity, focusing on the diagnostic clues and unusual morphological variants.
