Saturday, December 11, 2021

In a known case of VHL syndrome; PET/CT scan findings reveal multiple DOTANOC avid (somatostatin receptor expressing) dural based nodular and plaque-like lesions as described.

 





Somatostatin plays a role in physiological and pathological cell proliferation and angiogenesis. Five subtypes of somatostatin receptors have been identified, and the therapeutic use of somatostatin receptor-selective agonists has been reported in several diseases.



However, positron emission tomography/computed tomography with radiolabeled somatostatin analogs has shown clinical success because many neuroendocrine tumors overexpress somatostatin receptors.


Primary NENs versus NEN metastases to the brain, and that longer periods of surveillance are likely required for primary NENs. This is important because the prognosis between primary NENs and metastatic NENs to the brain are vastly different and should not be treated as equal diseases. An unfortunate patient eventually died of her recurrence secondary to complications of a ventriculoperitoneal shunt placed for treatment of hydrocephalus from the disease.


Brain metastases are associated with a poor prognosis, with a median overall survival is dismal from the diagnosis of CNS involvement. However, the leading cause of death in patients with metastatic CNS NENs is secondary to systemic disease progression itself, with the majority of cases being associated with organ dysfunction (eg, liver failure). When patients do present with metastatic NENs to the brain, they typically present with other local and distant metastases. Worsening headaches, nausea, and emesis.


Brain metastases (BM) are rarely reported in patients with neuroendocrine carcinoma (NEC) of non-lung origin and neuroendocrine tumors (NET) of the gastroenteropancreatic (GEP) or bronchopulmonary system. However, symptomatic brain metastases are associated with a dismal prognosis


Hence early detection and treatment could be advisable


Help before nemesis.


From the diagnosis of CNS involvement. However, the leading cause of death in patients with metastatic CNS NENs is secondary to systemic disease progression itself, with the majority of cases being associated with organ dysfunction (eg, liver failure).


When patients do present with metastatic NENs to the brain, they typically present with other local and distant metastases. Worsening headaches, nausea, and emesis.


Help before nemesis.


Brain metastases (BM) are rarely reported in patients with neuroendocrine carcinoma (NEC) of non-lung origin and neuroendocrine tumors (NET) of the gastroenteropancreatic (GEP) or bronchopulmonary system. However, symptomatic brain metastases are associated with a dismal prognosis.


Early detection and treatment could be advisable.

In the WHO classification of 2010, NETs were defined as neuroendocrine neoplasms and were classified as NET G1, NET G2, NEC (large cell or small cell type)


The disease is characterized by the growth of cysts and/or tumors. Tumors can either be benign or malignant. The characteristic tumor type in VHL is the hemangioblastoma, which is a benign tumor comprised of newly formed blood vessels.


Regional: Cancer has grown outside the pancreas into nearby tissues or has spread to nearby lymph nodes.


Distant: Cancer has spread to distant parts of the body such as the lungs, liver, or bones. 


Regional: Cancer has grown outside the pancreas into nearby tissues or has spread to nearby lymph nodes.


Distant: Cancer has spread to distant parts of the body such as the lungs, liver, or bones.





In the WHO classification of 2010, NETs were defined as neuroendocrine neoplasms and were classified as NET G1, NET G2, NEC (large cell or small cell type)


My first finding was


vHL disease is characterized by the growth of cysts and/or tumors. Tumors can either be benign or malignant. The characteristic tumor type in VHL is the hemangioblastoma, which is a benign tumor comprised of newly formed blood vessels.


Neuroendocrine tumors (NETs) are highly vascularized, but the process of proliferation and maturation of vascular structures during tumor development and progression has remained unknown.


Vascular endothelial growth factor (VEGF) is a signaling protein that promotes the growth of new blood vessels. VEGF forms part of the mechanism that restores the blood supply to cells and tissues when they are deprived of oxygenated blood due to compromised blood circulation.


HIF activation and increased expression of HIF targets, such as VEGF, have been linked to the development of pancreatic NETs.

HIF activation and increased expression of HIF targets, such as VEGF, have been linked to the development of pancreatic NETs.


However, calcification in PN as a criterion to determine benign nature is fallacious and can be misleading. The differential considerations of a calcified lesion include calcified granuloma, hamartoma, carcinoid, osteosarcoma, chondrosarcoma, and lung metastases/ primary bronchogenic carcinoma among others. We describe and illustrate different patterns of calcification as seen in PN on imaging.


Somatostatin Receptors – A NET is much more likely to express somatostatin receptors which can influence treatments such as somatostatin analogs and peptide receptor radiotherapy (PRRT) 


Often this is done with repeat imaging to see if the cyst grows over time. The best test to determine whether a cyst or tumor is benign or malignant is a biopsy. 


Although unusual/rare there is such a thing as cystic tumor 




NET metastases in the liver are typically solid, hypervascular lesions. 


Cysts and tumors are quite distinct entities.   However, some cysts can be partly solid. If the cyst has solid components, it may be benign or malignant and should have further evaluation.


Temporal paragangliomas can have one or more of the following symptoms:

  • hearing loss,
  • rhythmic thumping in the ear
  • , paralysis of the face, discharge from the ear, pain, vertigo, hemorrhage from the ear (otorrhagia),
  • lower cranial nerve paralysis,
  • nausea and vomiting,
  • vision problems,
  • headaches, and
  • changes in behavior.


Lung carcinoids are epithelial in origin and stain positive for cytokeratin. In addition, positive immunohistochemistry for various hormones, including serotonin, gastrin-releasing peptide (mammalian bombesin), pancreatic polypeptide, gastrin, human chorionic gonadotropin alpha subunit, leucine enkephalin, VIP, somatostatin, calcitonin,  ACTH, and the growth-hormone-releasing hormone is found in a majority of tumors.  Positive staining for multiple hormones is not uncommon Expression of  S-100 protein may occur, usually in peripheral tumors. The standard (hematopoietic) form of the adhesion molecule CD44 (CD44s) is usually expressed in  lung carcinoids and may be used for prognostic evaluation in typical carin


Pancreatic cancer is one of the most lethal malignancies in the world, with mortality rates being close to the incidence rates. The incidence rates of pancreatic cancer are 3%. Most patients with pancreatic cancer are diagnosed at the advanced stage due to the deficiency of a standard program for screening patients at a high risk of pancreatic cancer, leading to a poor prognosis with a 5-year survival rate of <7%. Therefore, it is very important to clarify the mechanisms of pancreatic cancer progression and develop novel therapeutic strategies to improve the overall survival of affected patients.


Previous studies have demonstrated that microRNAs (miRNAs/miRs) are implicated in the development of pancreatic cancer as both oncogenes or tumor suppressors.3,4 miRNAs regulate gene expression at the post-transcriptional level by binding to the complementary 3′-untranslated regions (3′-UTR) of target genes. Studies have shown that miRNAs are involved in many biological processes, such as proliferation, migration, and invasion, by regulating the expression of their target genes. Increasing evidence shows that miR-21 is markedly overexpressed in numerous types of cancer, including pancreatic cancer. It has been reported that miR-21 acts as an oncogene participating in the development of pancreatic cancers and may be utilized as a diagnostic or prognostic miRNA for pancreatic cancer.6–8 In pancreatic cancer, miR-21 decreased the expression of Slug and Fas ligand and influenced the growth, apoptosis, and invasion of pancreatic cancer cells.9,10 Another study indicated that miR-21 regulated the epithelial growth factor receptor/AKT signaling pathway through targeting Von Hippel-Lindau tumor suppressor (VHL) in glioblastomas; however, the function of the interaction of miR-21 and VHL in pancreatic cancer has remained elusive.


VHL is a component of the protein complex that includes belonging B, elongin C, and cullin-2, and possesses ubiquitin ligase E3 activity. When oxygen supply is adequate, hypoxia-inducible factor (HIF)-1α is hydroxylated by prolyl hydroxylase proteins and is then recognized by VHL, leading to the ubiquitination and degradation of HIF-1α.12 However, numerous types of solid tumors are anoxic; HIF-1α may be upregulated due to the inactivation of VHL, thus promoting the progression of tumors. VHL is a tumor suppressor inactivated in various types of tumors through diverse mechanisms, including the regulation by miRNAs. Numerous miRNAs have been reported to regulate the expression of VHL; for instance, miR-101 and13 miR-155.14 However, whether miR-21 and VHL contributed together to the development of pancreatic cancer remained to be clarified. The present study demonstrated that VHL is a direct and functional target of miR-21 and is downregulated in pancreatic cancer cells. Knockdown of miR-21 increased the expression of VHL and modulated the HIF-1α/vascular endothelial growth factor (VEGF) pathway, leading to inhibition of the malignant phenotypes of pancreatic cancer.



Lung carcinoids are epithelial in origin and stain positive for cytokeratin. In addition, positive immunohistochemistry for various hormones, including serotonin, gastrin-releasing peptide (mammalian bombesin), pancreatic polypeptide, gastrin, human chorionic gonadotropin alpha subunit, leucine enkephalin, VIP, somatostatin, calcitonin,  ACTH, and the growth-hormone-releasing hormone is found in a majority of tumors.  . Expression of  S-100 protein may occur, usually in peripheral tumors. The standard (hematopoietic) form of the adhesion molecule CD44 (CD44s) is usually expressed in  lung carcinoids and may be used for prognostic evaluation in typical carcin

Common symptoms on  presentation include

  •  cough, 
  • hemoptysis,
  •  wheezing,
  •  recurrent pneumonia with  or without persisting lung infiltrate on chest X-ray,
  •  dyspnea, and chest pain.
Some patients may have several years’ delay in the correct diagnosis due to misdiagnosis as asthma. Like other neuroendocrine tumors, lung carcinoids may secrete hormones. Endocrine symptoms are however rare. Despite serotonin, immunoreactivity is present in up to 84 % of the tumors, the classical carcinoid syndrome  with 

  • flush, 
  • diarrhea, 
  • bronchoconstriction, 
  • right-sided valvular heart disease and elevated urinary 5-hydroxyindolacetic acid is seen in only about 2–12 % of the patients, usually when liver metastases are present. This low frequency may in part be due to the high pulmonary content of monoamine oxidase, which metabolizes serotonin, but also to the fact that most lung carcinoids do not give rise to distant metastases. An atypical carcinoid syndrome with generalized 
  • flushing,  
  • edema, 
  • lacrimation, 
  • asthma, and 
  • diarrhea may occasionally be seen.
 This syndrome,  which must not be confused with atypical carcinoids, is caused by the secretion of histamine. An ectopic Cushing’s syndrome, caused by production of adrenocorticotropic hormone (ACTH) or corticotropin-releasing factor, may be seen in 2–6 % of patients with lung carcinoids. These tumors are often small and difficult to detect with conventional radiologic imaging.

Peripheral effects of serotonin are local vasoconstriction where it is released and also vasodilatation and increased capillary permeability; constriction of veins and induction of venous thrombosis and promotion of platelet aggregation.


Serotonin has a positive chronotropic effect on the heart through 5HT4 receptors and can cause cardiac rhythm disorders.


• Excessive serotonin gives rise to debilitating diarrhea affecting the quality of life of patients with carcinoid syndrome.


• Prolonged exposure to a high level of serotonin can cause fibrosis of heart valves, more commonly on the right side,


  • causing valvular heart disease. Excessive serotonin is also linked to fibrosis of the uterus, skin (scleroderma),


  • pulmonary and retroperitoneal fibrosis, in the long run, causing multiple complications.


Low levels of serotonin are often associated with many behavioral and emotional disorders.


  • Diarrhea

  • Indigestion

  • Blood sugar changes

  • Weight loss ( from 86 to 69 in 11 months)

  • Skin rash on face, stomach, or legs ( I have plenty)



  • difficulty speaking or loss of voice

  • a voice that is hoarse or wheezy

  • trouble drinking liquids and keep coughing 

  • pain in the ear

  • unusual heart rate fluctuations 

  • abnormal blood pressure and pulse

  • decreased appetite

  • Fear of food that again I would run to the loo

  • nausea or vomiting

  • abdominal bloating /pain


Also I still get diarrhea.

It was luck that Dr Hukku diagnosed and the SSTR thereafter, assured my diarrhea depressions would go away.


Dr Sajjan Rajpurohit administered 3 chemotherapy but my diarrhea and problems remained.


I paid a visit to Dr A.S.Soin



Haemangioblastomas are tumours of vascular origin and occur both sporadically and in patients with von Hippel Lindau (vHL). They are WHO grade I tumours that can occur in the central nervous system or elsewhere in the body, including kidneys, liver, and pancreas.Haemangioblastoma is actually a capillary haemangioma and, despite the name with the affix of "blastoma", it is a low grade (WHO grade I) lesion (note that the calvarial haemangioma is a cavernous haemangioma).



Venous malformations are characterized by a soft, compressible, nonpulsatile tissue mass.


Looking at tumour cells in the spinal fluid under high-resolution MRI scans are all that is necessary for an accurate diagnosis. A biopsy isn't required for diagnosis as it may cause meningitis and blood loss thereby cell spillage.


Dr Soin's opinion was



Dr. Soin said " Look Payel you have suffered a lot but you have to win this war".






Calcified lesions in spleen : Calcified splenic granulomas are a common incidental finding, most commonly resulting from tuberculosis or histoplasmosis and less commonly from Pneumocystis carinii pneumonia or brucellosis...Few specks of calcification noted in splenic parenchyma


MILD RELATIVE LYMPHOCYTOSIS NOTED.

PLATELETS NORMAL IN NUMBER AND MORPHOLOGY.


  • Infection (bacterial, viral, other)

  • Cancer of the blood or lymphatic system

  • An autoimmune disorder causing ongoing (chronic) inflammation

Current research suggests that lymphopenia, defined as a low lymphocyte count, is commonly present in patients with COVID-19. There is also evidence that the degree of lymphopenia correlates with illness severity in patients with COVID-19.

Strong evidence has been accumulated since the beginning of the COVID-19 pandemic that neutrophils play an important role in the pathophysiology, particularly in those with severe disease courses. While originally considered to be a rather homogeneous cell type, recent attention to neutrophils has uncovered their fascinating transcriptional and functional diversity as well as their developmental trajectories. These new findings are important to better understand the many facets of neutrophil involvement not only in COVID-19 but also many other acute or chronic inflammatory diseases, both communicable and non-communicable. Here, we highlight the observed immune deviation of neutrophils in COVID-19 and summarize several promising therapeutic attempts to precisely target neutrophils and their reactivity in patients with COVID-

19

My COVID has no reIationship here.



Calcification in PN as a criterion to determine benign nature is fallacious and can be misleading. The differential considerations of a calcified lesion include calcified granuloma, hamartoma, carcinoid, osteosarcoma, chondrosarcoma and lung metastases or a primary bronchogenic carcinoma among others. We describe and illustrate different patterns of calcification as seen in PN on imaging.

Calcification in a pulmonary nodule (PN) on imaging indicates a high probability that the lesion is benign. But not all calcified PN are benign and the differential considerations include a primary central lung carcinoid, metastasis and a primary bronchogenic carcinoma.

Bronchogenic carcinoma is any type or subtype of lung cancer. The term was once used to describe only certain lung cancers that began in the bronchi and bronchioles, the passageways to the lungs. However, today it refers to any type.

Symptoms


  • persistent or worsening cough

  • wheezing

  • coughing up blood and mucus

  • chest pain that gets worse when you take a deep breath, laugh, or cough

  • shortness of breath

  • hoarseness

  • weakness, fatigue

  • frequent or persistent attacks of bronchitis or pneumonia

Symptoms that cancer has spread may include:


  • hip or back pain

  • headache, dizziness, or seizures

  • numbness in an arm or leg

  • yellowing of the eyes and skin (jaundice)

  • enlarged lymph nodes

  • unexplained weight loss

I t means you have one of a group of conditions that cause lung cysts -- sacs of tissue filled with air or fluid.


Lung cysts have many potential causes and can cause severe complications without detection and treatment.

The significance of these observations is that they strongly implicate PNECs as proinflammatory cells, functionally linked to a myriad of pathological conditions, including asthma, cystic fibrosis, COPD and cancer.


Centrilobular emphysema, or centriacinar emphysema, is a long-term, progressive lung disease. It’s considered to be a form of chronic obstructive pulmonary disease (COPD).


Centrilobular emphysema primarily affects the upper lobes of the lungs. It’s characterized by damage to your respiratory passageways. Known as bronchioles, these passageways allow airflow from your mouth and nose to your lungs.


Mediastinal lymph nodes are lymph nodes located in the mediastinum. The mediastinum is the area located between the lungs which contains the heart, esophagus, trachea, cardiac nerves, thymus gland, and lymph nodes of the central chest.


The enlargement of lymph nodes is referred to as lymphadenopathy. Mediastinal lymphadenopathy generally suggests a problem related to lungs, whether benign or malignant.


Calcified splenic granulomas are a common incidental finding, most commonly resulting from tuberculosis or histoplasmosis and less commonly from Pneumocystis carinii pneumonia or brucellosis. A risk factor for many of these infections is HIV infection.



. A well-defined avidly enhancing

subserosal lesion measuring 3x2.6 cm is seen at the uterine fundus.: Uterine fibroids are a major cause of morbidity . There are several factors that are attributed to underlie the development and incidence of these common tumors, but this further corroborates their relatively unknown etiology. The most likely presentation of fibroids is by their effect on the woman’s menstrual cycle or pelvic pressure symptoms.



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