Nevoid Basal Cell Carcinoma Syndrome

Sebaceous Tumors 101 (sebaceous hyperplasia vs sebaceous adenoma vs sebaceous carcinoma)
Sebaceous Tumors 101 (sebaceous hyperplasia vs sebaceous adenoma vs sebaceous carcinoma) administrator 1 Views • 2 years ago

Excerpt from "Dermatopathology Pearls for Head & Neck / Oral & Maxillofacial Pathologists" (full video: https://kikoxp.com/posts/6020). Presented at the American Academy of Oral & Maxillofacial Pathology (AAOMP) 2021 Annual Meeting (Virtual), May 2021.

A complete organized library of all my videos, digital slides, pics, & sample pathology reports is available here: https://kikoxp.com/posts/5084 (dermpath) & https://kikoxp.com/posts/5083 (bone/soft tissue sarcoma pathology).

Please check out my Soft Tissue Pathology & Dermatopathology survival guide textbooks: http://bit.ly/2Te2haB

This video is geared towards medical students, pathology or dermatology residents, or practicing pathologists or dermatologists. Of course, this video is for educational purposes only and is not formal medical advice or consultation.

Presented by Jerad M. Gardner, MD. Please subscribe to my channel to be notified of new pathology teaching videos.

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كل ما تريد ان تعرفه عن سرطان المخ
كل ما تريد ان تعرفه عن سرطان المخ administrator 6 Views • 2 years ago

دليل لسرطان الدماغ
1-ما هو؟
مثل أي جزء آخر من جسمك ، يمكن أن يكون لدماغك ورم ، والذي يحدث عندما تنمو الخلايا خارج نطاق السيطرة وتشكل كتلة صلبة. نظرًا لأن دماغك يحتوي على أنواع عديدة من الخلايا ، فيمكن أن يصاب بالعديد من أنواع الأورام. البعض مصاب بالسرطان والبعض الآخر ليس كذلك. بعضها ينمو بسرعة والبعض الآخر ببطء. ولكن نظرًا لأن دماغك هو مركز التحكم في جسمك ، عليك أن تأخذهم جميعًا على محمل الجد.
2-أورام المخ
جمجمتك صلبة ، ودماغك رخو ، ولا يوجد حقًا مكان في رأسك لأي شيء آخر. عندما ينمو الورم ، فإنه يضغط على دماغك لأنه لا يوجد مكان يذهب إليه. يمكن أن يؤثر ذلك على طريقة تفكيرك ورؤيتك وتصرفك وشعورك. لذلك مع أورام الدماغ ، سواء أكانت سرطانية أم لا ، ما يهم هو مكان وجودها ، ومدى سرعة وسهولة نموها أو انتشارها ، وما إذا كان طبيبك يستطيع التخلص منها.
3- سرطان الدماغ الثانوي
يعاني معظم الأشخاص المصابين بسرطان الدماغ (حوالي 100000 كل عام) من هذا النوع ، مما يعني أن السرطان في جزء آخر من الجسم قد انتشر إلى عقلك. حوالي نصف سرطانات الدماغ تبدأ في شكل سرطان الرئة. تشمل أنواع السرطان الأخرى التي يمكن أن تنتشر إلى دماغك ما يلي:
• سرطان الثدي
• سرطان القولون
• سرطان الكلى
• سرطان الدم
• سرطان الغدد الليمفاوية
• الورم الميلانيني (سرطان الجلد)
4-أورام الدماغ الأولية
عند البالغين ، فإن الأورام الأكثر شيوعًا التي تبدأ في الدماغ هي الأورام السحائية meningiomas والأورام الدبقية gliomas..
تشكل الأورام السحائية أكثر من 35٪ من جميع أورام الدماغ الأولية. إنها لا تنمو من أنسجة المخ نفسها ، ولكن من الخلايا الموجودة في غطاء الدماغ. موقعها غير السرطاني ونموها يجعلها خطيرة.
أكثر أورام الدماغ السرطانية شيوعًا - تقريبًا 1 من كل 5 - هي الأورام الأرومية الدبقية glioblastomas. إنه نوع من الورم الدبقي glioma ، الأورام التي تبدأ في الخلايا الدبقية. تنتشر بسرعة وغالبا ما تكون قاتلة.
بشكل عام ، هناك زيادة في عدد الأشخاص الذين تم تشخيص إصابتهم بأورام الدماغ. قد يكون ذلك جزئيًا لأن التكنولوجيا تجعل رؤيتهم أسهل. لكن الباحثين يبحثون أيضًا في الأسباب المحتملة الأخرى ، مثل الأشياء في البيئة.
5- أنواع أخرى
تمت تسمية الأنواع المختلفة من أورام الدماغ الأولية على اسم المكان الذي بدأت فيه في دماغك. إلى جانب الأورام الدبقية ، تشمل الأورام الغدية adenomas (في الغدة النخامية pituitary gland) ، والأورام الحبلية chordomas (الجمجمة والعمود الفقري) ، والأورام الأرومية النخاعية medulloblastomas (المخيخ cerebellum) ، والساركوما (أنسجة المخ) ، من بين أمور أخرى.
+6+ درجات
يصنف الأطباء أورام المخ بدرجة من 1 إلى 4. أورام الدرجة المنخفضة (الدرجة 1) ليست سرطانية. تنمو ببطء ولا تنتشر عادة. يمكن علاجها عادةً إذا كان بإمكان طبيبك إخراجها بالجراحة. في الطرف الآخر ، الأورام عالية الدرجة (الدرجة 4) هي سرطان. تنمو بسرعة ، وتنتشر بسرعة ، وعادة لا يمكن علاجها. يقع الصفان 2 و 3 بينهما. عادة ، الصف الثاني ليس سرطانًا والصف الثالث ليس سرطانًا.
7- الأعراض
تعتمد هذه على نوع الورم الذي تعاني منه ومكان وجوده ، ولكن يمكنك:
• التصرف بطرق لا تفعلها عادة
• تشعر بالنعاس طوال اليوم
• تجد صعوبة في التعبير عن نفسك ، مثل عدم العثور على الكلمات الصحيحة أو الشعور بالارتباك
• الإصابة بالصداع بشكل متكرر وخاصة في الصباح
• لديك مشاكل في الرؤية ، مثل عدم وضوح الرؤية أو ازدواجها
• تفقد توازنك بسهولة أو لديك مشاكل في المشي
• تشنجات
8- عوامل الخطر: الإشعاع
عادة ما يكون من غير الواضح ما الذي يعرضك لخطر الإصابة بورم الدماغ الأولي - الورم الذي يبدأ في دماغك. لكن أحد الأسباب المعروفة هو توجيه الإشعاع إلى رأسك لعلاج حالة طبية أخرى ، مثل اللوكيميا. في معظم هذه الحالات ، تفوق فائدة الإشعاع خطر تسببه في الإصابة بالسرطان في المستقبل.
9- عوامل الخطر: العمر
يمكن أن تصاب بورم المخ في أي عمر ، لكن الأطفال والبالغين يميلون إلى الإصابة بأنواع مختلفة. وهي أكثر شيوعًا بين البالغين فوق سن الخمسين منها لدى الشباب والأطفال.
10-عوامل الخطر: مشاكل صحية أخرى
قد تكون أكثر عرضة للإصابة بورم في المخ إذا كان لديك جهاز مناعي ضعيف ، كما لو كنت مصابًا بالإيدز ، أو أجريت لك عملية زرع عضو. وينطبق الشيء نفسه إذا كانت أورام المخ موجودة في عائلتك أو إذا كان لديك أحد هذه الحالات بسبب الجينات المسببة للمشكلة:
• متلازمة Li-Fraumeni
• الورم العصبي الليفي Neurofibromatosis من النوع 1 أو 2
• متلازمة سرطان الخلايا القاعدية
• Nevoid basal cell carcinoma syndrome

• • التصلب الحدبي Tuberous sclerosis

• متلازمة توركوت Turcot syndrome من النوع 1 أو 2
• مرض فون هيبل لينداو
• Von Hippel-Lindau disease

11-هل تسبب الهواتف المحمولة سرطان الدماغ؟
كان هذا موضوعًا ساخنًا في السنوات الأخيرة ، لكن الأبحاث لم تظهر أي صلة واضحة بين الهواتف المحمولة وأورام الدماغ. لا توجد العديد من الدراسات طويلة المدى حول استخدام الهاتف الخلوي ، ولا يزال العلماء يدرسون ذلك. حتى نعرف المزيد ، يمكن أن يؤدي استخدام سماعات الأذن أو أي جهاز آخر بدون استخدام اليدين إلى إبعاد هاتفك عن رأسك وتقليل تعرضك.
12-كيف وجدت
لا يقوم الأطباء عمومًا بإجراء فحوصات روتينية لسرطان الدماغ كما يفعلون مع بعض الأنواع الأخرى. عادة ما تكتشف ذلك عندما تذهب إلى طبيبك مع الأعراض وتجري الاختبارات. تميل خيارات العلاج ومدى نجاحها إلى الاعتماد بشكل أكبر على نوع الورم وحجمه وموقعه وعمرك أكثر مما تعتمد عليه عندما تجده.
13 - الاختبارات
14- العلاج: الانتظار اليقظ
: Watchful Waiting

CNS TX II UPDATES II WHO 5TH E II POST GRADUATE RESIDENCY II MD DNB
CNS TX II UPDATES II WHO 5TH E II POST GRADUATE RESIDENCY II MD DNB administrator 2 Views • 2 years ago

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00:00 INTRO
02:15 UPDATES IN GLIOMAS
20:28 UPDATES IN EMBRYONAL TXS
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odontogenic keratocyst okc
odontogenic keratocyst okc administrator 1 Views • 2 years ago

#oceanofdentistry #OCEANOFDENTISTRY
oral pathology#odontogenickeratocyst#cyst#odontogeniccyst#dentigerouscyst#radicularcyst#okc#eruptioncyst
An odontogenic keratocyst is a rare and benign but locally aggressive developmental cyst. It most often affects the posterior mandible and most commonly presents in the third decade of life. Odontogenic keratocysts make up around 19% of jaw cysts.
In the WHO/IARC classification of head and neck pathology, this clinical entity had been known for years as the odontogenic keratocyst; it was reclassified as keratocystic odontogenic tumour (KCOT) from 2005 to 2017. In 2017 it reverted to the earlier name, as the new WHO/IARC classification reclassified OKC back into the cystic category. Under The WHO/IARC classification, Odontogenic Keratocyst underwent the reclassification as it is no longer considered a neoplasm due to a lack of quality evidence regarding this hypothesis, especially with respect to clonality. Within the Head and Neck pathology community there is still controversy surrounding the reclassification, with some pathologists still considering Odontogenic Keratocyst as a neoplasm in line with the previous classificationOdontogenic keratocysts originate from the odontogenic epithelium (dental lamina) in the alveolus left from tooth development stages. They are mainly thought to arise from rests of Serres.Multiple odontogenic keratocysts are a feature, and major diagnostic criteria, of nevoid basal cell carcinoma syndrome (NBCCS, also known as Gorlin-Goltz Syndrome). Almost all individuals with NBCCS have odontogenic keratocysts which require numerous treatments. Consideration of the syndrome needs to be taken into account if found in children or if multiple OKCs are present; diagnosis of multiple OKCs in a child necessitates referral for genetic evaluation. Histologically, the cysts are indistinguishable to non-syndromic cysts and over 80% will have PTCH mutationRadiographs of odontogenic keratocysts show well-defined radiolucent areas with rounded or scalloped margins which are well demarcated.These areas can be multilocular or unilocular. The growth pattern of the lesion is very characteristic from which a diagnosis can be made as there is growth and spread both forward and backward along the medullary cavity with little expansion. No resorption of teeth or inferior dental canal and minimal displacement of teeth is seen. Due to lack of expansion of the odontogenic keratocyst, the lesion can be very large when radiographically discovered.Radiologically
Odontogenic myxomaAmeloblastomaCentral giantcellgranulomaAdenomatoid odontogenic tumorDentigerous cyst (follicular cyst)
Histologically
Orthokeratocyst
Radicular cyst (particularly if the OKC is very inflamed)
Ameloblastoma
Histology
Odontogenic keratocysts have a diagnostic histological appearance. Under the microscope, OKCs vaguely resemble keratinized squamous epithelium; however, they lack rete ridges and often have an artifactual separation from their basement membrane.
The fibrous wall of the cyst is usually thin and uninflamed. The epithelial lining is thin with even thickness and parakeratinised with columnar cells in the basal layer which have focal reverse polarisation (nuclei are on the opposite pole of the cell).The basal cells are an indication of the odontogenic origin as they resemble pre-ameloblasts. The epithelium can separate from the wall, resulting in islands of epithelium. These can go on to form 'satellite' or 'daughter' cysts, leading to an overall multilocular cyst. Presence of daughter cysts is particularly seen in those with NBCCS. Inflamed cysts show hyperplastic epithelium which is no longer characteristic of OKCs and can have resemblance to radicular cysts instead. Due to areas of focal inflammation, a larger biopsy is required for correct diagnosis of odontogenic keratocysts.Treatment options:
Surgical enucleation: surgical removal of the entire epithelial lining of the cyst.
Marsupialisation followed by enucleation: this method is carried out by surgeons for larger cysts.
Curettage involving simple excision and scraping-out of cavity.
Carnoy's solution fixative (ethanol, chloroform and acetic acid) which is usually used in conjunction with excision and curretage. Cavity wall can be treated with the fixative either before enucleation to kill the lining of the wall or added after curretage to bony walls, killing any residual epithelial cells to a depth of 1-2mm. Used with care near mandibular canal and the neurovascular bundle within.
Marsupialization
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Gorlin syndrome model from induced neural progenitor cells exhibiting constitutive GLI1 expression
Gorlin syndrome model from induced neural progenitor cells exhibiting constitutive GLI1 expression administrator 6 Views • 2 years ago

The hedgehog signaling pathway is a vital factor for embryonic development and stem cell maintenance. Dysregulation of its function results in tumor initiation and progression. The aim of this research was to establish a disease model of hedgehog-related tumorigenesis with Gorlin syndrome-derived induced pluripotent stem cells (GS-iPSCs). Induced neural progenitor cells from GS-iPSCs (GS-NPCs) show constitutive high GLI1 expression and higher sensitivity to smoothened (SMO) inhibition compared with wild-type induced neural progenitor cells (WT-NPCs). The differentiation process from iPSCs to NPCs may have similarity in gene expression to Hedgehog signal-related carcinogenesis. Therefore, GS-NPCs may be useful for screening compounds to find effective drugs to control Hedgehog signaling activity.

Summary
The hedgehog signaling pathway is a pivotal pathway for basal cell carcinoma and
medulloblastoma. Gorlin syndrome-derived induced pluripotent stem cells (iPSCs) with a heterozygous mutation of PTCH1, one of the hedgehog target genes, exhibited high GLI1 expression and enhanced sensitivity to the hedgehog pathway inhibitor after neural differentiation. These iPSCs can serve a good model of the hedgehog pathway-related tumors.

Background: The hedgehog signaling pathway is a vital factor for embryonic development and stem cell maintenance. Dysregulation of its function results in tumor initiation and progression. The aim of this research was to establish a disease model of hedgehog-related tumorigenesis with Gorlin syndrome-derived induced pluripotent stem cells (GS-iPSCs), with a heterozygous mutation of PTCH1.

Methods: We induced neural progenitor cells from GS-iPSCs with the SFEBq method. Their expression levels of the hedgehog related genes and reactions to SMO inhibitor (Vismodegib) and agonist (SAG) were evaluated by quantitative real-time PCR.

Results: Induced neural progenitor cells from GS-iPSCs showed constitutive high GLI1 expression and higher sensitivity to smoothened inhibition compared to wild-type induced neural progenitor cells.

Conclusions: Neural progenitor cells from GS-iPSCs may be useful for compounds screening to find effective drugs to control Hedgehog signaling activity.





Introduction
The hedgehog (Hh) signaling pathway plays an important role in embryogenesis and stem cell maintenance. Ectopic Hh signal up-regulation causes tumors such as basal cell carcinoma (BCC) and medulloblastoma. Hh signaling is also related to other malignancies such as breast cancer, pancreatic cancer, lung cancer, and prostate cancer6. A lot of medications have been under research to establish treatment and prevention of Hh signaling pathway-related tumors. The Hh signaling pathway can be initiated by three ligands: desert hedgehog (DHH), Indian hedgehog (IHH) or sonic hedgehog (SHH)8. These proteins bind to the 12-pass transmembrane protein receptor PTCH1. Once ligand binding occurs, the PTCH1 receptor relieves its inhibitory action on smoothened (SMO), a 7-pass transmembrane G-protein-coupled signal transduction molecule, which then activates a signaling cascade resulting in the translocation of Gli transcription factors to the nucleus. In the absence of the ligand, SMO is normally localized in vesicles. When the pathway is activated, SMO localizes to the primary cilium on the cell membrane.

Gorlin syndrome (GS) or nevoid basal cell carcinoma syndrome (NBCCS; OMIM 109400) is a rare autosomal dominantly inherited disorder that is characterized by congenital anomalies and development of tumors such as basal cell carcinoma and medulloblastoma. GS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Haploinsufficiency of PTCH1 results in constitutive activation of the Hh signaling pathway. Multiple genes that influence embryogenesis and pluripotency are oncogenes that drive the development of tumors. Additionally, some mechanisms of tumorigenesis are similar to embryonic development. GS patients frequently develop medulloblastoma at a young age compared to patients with sporadic cases, because mutation of PTCH1 causes dysregulation of the Hh signaling pathway during development of the cerebellum, which can lead to medulloblastoma.

In this study, we generated GS-iPSCs with a heterozygous mutation of PTCH1, and induced neural progenitor cells (NPCs) from GS-iPSCs. Neural progenitors from GS-iPSCs expressed GLI1, a downstream target gene of Hh signaling and exhibited sensitivity to Vismodegib, an SMO inhibitor. Induced neural progenitor cells from Gorlin syndrome iPSCs may therefore serve a good precancerous model for Hh related tumors.


KEYWORDS:
GLI1; PTCH1; hedgehog signaling pathway; induced pluripotent stem cells; vismodegib


#Gohlin syndrome #biomarker #iPSC #iPS cell

Hajime Ikehara 20161222091403

odontogenic keratocyst  |okc|
odontogenic keratocyst |okc| administrator 4 Views • 2 years ago

#oceanofdentistry #OCEANOFDENTISTRY
oral pathololgy#odontogeniccyst#cyst#okc #odontogenickeratocyst
An odontogenic keratocyst is a rare and benign but locally aggressive developmental cyst. It most often affects the posterior mandible and most commonly presents in the third decade of life. Odontogenic keratocysts make up around 19% of jaw cysts.
In the WHO/IARC classification of head and neck pathology, this clinical entity had been known for years as the odontogenic keratocyst; it was reclassified as keratocystic odontogenic tumour (KCOT) from 2005 to 2017. In 2017 it reverted to the earlier name, as the new WHO/IARC classification reclassified OKC back into the cystic category. Under The WHO/IARC classification, Odontogenic Keratocyst underwent the reclassification as it is no longer considered a neoplasm due to a lack of quality evidence regarding this hypothesis, especially with respect to clonality. Within the Head and Neck pathology community there is still controversy surrounding the reclassification, with some pathologists still considering Odontogenic Keratocyst as a neoplasm in line with the previous classificationOdontogenic keratocysts originate from the odontogenic epithelium (dental lamina) in the alveolus left from tooth development stages. They are mainly thought to arise from rests of Serres.Multiple odontogenic keratocysts are a feature, and major diagnostic criteria, of nevoid basal cell carcinoma syndrome (NBCCS, also known as Gorlin-Goltz Syndrome). Almost all individuals with NBCCS have odontogenic keratocysts which require numerous treatments. Consideration of the syndrome needs to be taken into account if found in children or if multiple OKCs are present; diagnosis of multiple OKCs in a child necessitates referral for genetic evaluation. Histologically, the cysts are indistinguishable to non-syndromic cysts and over 80% will have PTCH mutationRadiographs of odontogenic keratocysts show well-defined radiolucent areas with rounded or scalloped margins which are well demarcated.These areas can be multilocular or unilocular. The growth pattern of the lesion is very characteristic from which a diagnosis can be made as there is growth and spread both forward and backward along the medullary cavity with little expansion. No resorption of teeth or inferior dental canal and minimal displacement of teeth is seen. Due to lack of expansion of the odontogenic keratocyst, the lesion can be very large when radiographically discovered.Radiologically
Odontogenic myxomaAmeloblastomaCentral giantcellgranulomaAdenomatoid odontogenic tumorDentigerous cyst (follicular cyst)
Histologically
Orthokeratocyst
Radicular cyst (particularly if the OKC is very inflamed)
Ameloblastoma
Histology
Odontogenic keratocysts have a diagnostic histological appearance. Under the microscope, OKCs vaguely resemble keratinized squamous epithelium; however, they lack rete ridges and often have an artifactual separation from their basement membrane.
The fibrous wall of the cyst is usually thin and uninflamed. The epithelial lining is thin with even thickness and parakeratinised with columnar cells in the basal layer which have focal reverse polarisation (nuclei are on the opposite pole of the cell).The basal cells are an indication of the odontogenic origin as they resemble pre-ameloblasts. The epithelium can separate from the wall, resulting in islands of epithelium. These can go on to form 'satellite' or 'daughter' cysts, leading to an overall multilocular cyst. Presence of daughter cysts is particularly seen in those with NBCCS. Inflamed cysts show hyperplastic epithelium which is no longer characteristic of OKCs and can have resemblance to radicular cysts instead. Due to areas of focal inflammation, a larger biopsy is required for correct diagnosis of odontogenic keratocysts.Treatment options:
Surgical enucleation: surgical removal of the entire epithelial lining of the cyst.
Marsupialisation followed by enucleation: this method is carried out by surgeons for larger cysts.
Curettage involving simple excision and scraping-out of cavity.
Carnoy's solution fixative (ethanol, chloroform and acetic acid) which is usually used in conjunction with excision and curretage. Cavity wall can be treated with the fixative either before enucleation to kill the lining of the wall or added after curretage to bony walls, killing any residual epithelial cells to a depth of 1-2mm. Used with care near mandibular canal and the neurovascular bundle within.
Marsupialization
contact us :
Telegram :
https://t.me/joinchat/clP8fKn1d15jM2Fl
gmail: oceanofdentistry@gmail.com
Insta gram : ocean_of_dentistry
Fb:. https://www.facebook.com/ocean...._of_dentistry-100706
Whatsapp for notes :https://chat.whatsapp.com/E4sX2QPn29S1ikFbnXnN83

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