Sandbox:Haytham

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]

WHO classification of tumors of CNS

B01

B02

B03

D01

D02

D03

D04

D05

Risk stratification criteria

Standard risk group Patients aged over 3 years Categorised as M0 by craniospinal MRI and CSF sampling <1.5 cm2 residual disease after resection

Standard risk group Patients aged over 3 years Categorised as M0 by craniospinal MRI and CSF sampling <1.5 cm2 residual disease after resection unfavourable histopa-thology

• Based on stage, patients are classified into standard (average) and high risk, with standard risk accounting for most patients (about half to two-thirds) and high risk accounting for the remainder. Standard risk patients are those patients aged over 3 years, with <1.5 cm2 residual disease after resection and categorised as M0 by craniospinal MRI and CSF sampling. High risk patients are all those who have had a subtotal resection with >1.5 cm2 residual tumour on immediatepostoperative imaging and/or metastatic disease (leptomeningeal seeding, M1e3) or unfavourable histopa-thology [19]. M4 disease at the time of first diagnosis is virtually never seen.

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World Health Organization 2007 (WHO) classification

classic: dense sheet like growth of cells hyperchromatic round-to-oval nuclei increased mitotic activity conspicuous apoptosis neuroblastic or Homer-Wright rosettes (neoplastic cell nuclei disposed in a radial arrangement around fibrillary processes) are common features necrosis is less common

desmoplastic: more common in adults once termed "circumscribed arachnoidal cerebellar sarcoma"

extensively nodular with neuronal differentiation: usually in children less than 3 years of age also known as cerebellar neuroblastoma "grapelike" macroscopic nodularity intranodular: cellular uniformity fine fibrillary matrix occasional mature ganglion cells

large cell / anaplastic​: ​​rarest histologic subtype high mitotic activity and pleomorphism large round nuclei with variable eosinophilic cytoplasm not distinguishable on imaging from other types haemorrhage and necrosis is common

Multiple myeloma summary.

Durie-Salmon staging system

First published in 1975, the Durie-Salmon staging system is still in use, but has largely been superseded by the simpler ISS:

• stage 1: all of
  • Hb > 10g/dL
  • normal calcium
  • Skeletal survey: normal or single plasmacytoma or osteoporosis
  • Serum paraprotein level < 5 g/dL if IgG, < 3 g/dL if IgA
  • Urinary light chain excretion < 4 g/24h
• stage 2: fulfilling the criteria of neither 1 nor 3
• stage 3: one or more of
  • Hb < 8.5g/dL
  • high calcium > 12mg/dL
  • Skeletal survey: 3 or more lytic bone lesions
  • Serum paraprotein >7g/dL if IgG, > 5 g/dL if IgA
  • Urinary light chain excretion > 12g/24h

Stage	Hemoglobin level	Calcium level	Skeletal survey	Serum paraprotein level	Urinary light chain excretion
Stage 1	> 10g/dL	8.5-10.2 mg/dL	Normal or single plasmacytoma or osteoporosis	< 5 g/dL if IgG or < 3 g/dL if IgA	< 4 g/24h
Stage 2	8.5-10g/dL	10.2-12 mg/dL	fulfilling the criteria of neither 1 nor 3	5-7 g/dL if IgG or 3-5 g/dL if IgA	4-12 g/24h
Stage 3	< 8.5g/dL	> 12mg/dL	3 or more lytic bone lesions	>7g/dL if IgG or > 5 g/dL if IgA	> 12g/24h

The table below lists the genetic risk factors for multiple myeloma:

Genetic Risk Factor	Description
Age	The chance to develop multiple myeloma increases as patients get older, where only 1% of multiple myeloma cases are diagnosed in patients younger than 35 years.
Gender	Males are more commonly affected with multiple myeloma than females. The male to female ratio is approximately 2 to 1
Lynch Syndrome AKA Hereditary Non-polyposis Colorectal Cancer (HNPCC)	AD inheritance; caused by a defect in one of the mismatch repair genes, most commonly hMLH1, hMSH2, hMSH6, or PMS2; the mean age at initial cancer diagnosis is around 48 years

The table below lists the risk factors for multiple myeloma:

Risk Factor	Description
Age	The chance to develop multiple myeloma increases as patients get older, where only 1% of multiple myeloma cases are diagnosed in patients younger than 35 years
Race	African American and Native Pacific Islanders descents are at increased risk of developing multiple myeloma
Gender	Males are more commonly affected with multiple myeloma than females. The male to female ratio is approximately 2 to 1
Having other plasma cell diseases	Studies have shown that patients with other plasma cell diseases such as monoclonal gammopathy of undetermined significance develop multiple myeloma later in their lives.
Family history	A familial predisposition to myeloma exists due to hyperphosphorylation of specific proteins that may contribute to a higher rates of multiple myeloma in certain groups.
Obesity	A study by the American Cancer Society found that being overweight increases a person's risk of developing multiple myeloma
Workplace exposures	Petroleum workers and farmers tend to have higher incidence of multiple myeloma relative to other occupations
Radiation	Areas with previous history of atoms bombs or nuclear accidents had higher risk of multiple myeloma due to increased rate of radiation exposure

The table below lists the genetic risk factors for multiple myeloma:

Genetic Risk Factor	Description
Age	The chance to develop multiple myeloma increases as patients get older, where only 1% of multiple myeloma cases are diagnosed in patients younger than 35 years.
Gender	Males are more commonly affected with multiple myeloma than females. The male to female ratio is approximately 2 to 1
Lynch Syndrome AKA Hereditary Non-polyposis Colorectal Cancer (HNPCC)	AD inheritance; caused by a defect in one of the mismatch repair genes, most commonly hMLH1, hMSH2, hMSH6, or PMS2; the mean age at initial cancer diagnosis is around 48 years

The table below lists common prognostic factors for multiple myeloma:

Prognostic Factor	Description
Stage	As with most cancers, the higher the stage of multiple myeloma, the more poor is the outcome.
Kidney function	An elevated level of creatinine is considered a poor prognostic factors.
Labelling index	The labeling index indicates how fast the cancer cells are growing. A high plasma cell labeling index (PCLI) or proliferation (reproduction) rate is a poor prognostic factor.
Age	Older patients have worse prognosis than younger patients.
Chromosome changes	Cytogenetic analysis of multiple myeloma cells may be of prognostic value, with deletion of chromosome 13, non-hyperdiploidy and the balanced translocations t(4;14) and t(14;16) conferring a poorer prognosis. The 11q13 and 6p21 cytogenetic abnormalities are associated with a better prognosis.Canadian cancer society (2015)http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/prognosis-and-survival/?region=mb Accessed on September, 20th 2015</ref>
Assocciated plasma cell disorder	The presence of plasma cell leukemia or soft tissue plasmacytomas is associated with a particularly poor prognosis among patients with multiple myeloma.
Performance status	Performance status is ranked on a 0–4 scale. The lower the number, the healthier and more active the person is, and the better the prognosis. Performance status is important in multiple myeloma because people who are healthier can withstand more intensive treatment.
Blood tests	Abnormal blood tests play an important role in determining prognosis in people with multiple myeloma.
Beta-2-microglobulin	A higher level of beta-2-microglobulin predicts a poorer prognosis.
Albumin level	A lower albumin level predicts poorer prognosis.
Lactate dehydrogenase level	A higher level of lactate dehydrogenase (LDH) predicts a poorer prognosis.
Response to treatment	People whose cancer responds to treatment and goes into complete remission have a better prognosis than people whose cancer does not respond to the initial treatment.

Stratification of Treatment Based on Transplant Eligibility

Transplant-Eligible Patients

• According to the Myeloma Mayo Stratification of Myeloma and Risk-Adapted Therapy (Myeloma M-SMART), medical therapy for transplant-eligible patients is individualized based on the patient risk.
• The algorithm is shown below:

Treatment for patients with multiple myeloma who are transplant-eligible

High risk

Intermediate risk

Standard risk

4 cycles of bortezomib-lenalidomide-dexamethasone

4 cycles of cyclophosphamide-bortezomib-dexamethasone

4 cycles of either bortezomib-lenalidomide-dexamethasone or cyclophosphamide-bortezomib-dexamethasone

Collect stem cells

Collect stem cells

Collect stem cells

Autologous stem cell transplant (especially if patient is not in complete remission)

Autologous stem cell transplant

Autologous stem cell transplant

Bortezomib-lenalidomide-dexamethasone for > 1 year

Bortezomib-based therapy for > 1 year

Consider lenalidomide maintenance

Continue lenalidomide-dexamethasone

Transplant-Ineligible Patients

• According to the Myeloma Mayo Stratification of Myeloma and Risk-Adapted Therapy (Myeloma M-SMART), medical therapy for transplant-ineligible patients is also individualized based on the patient risk.
• The algorithm is shown below:

Treatment for patients with multiple myeloma who are transplant-ineligible

High risk

Intermediate risk

Standard risk

Bortezomib-lenalidomide-dexamethasone

Either melphalan-prednisone + weekly bortezomib or weekly cyclophosphamide-bortezomib-dexamethasone

Either lenalidomide-dexamethasone or melphalan-prednisone-thalidomide

Bortezomib maintenance

Observation

WHO 2007 histological classification system

Classic medulloblastoma

Variant medulloblastoma

Desmoplastic medulloblastoma

Large cell medulloblastoma

Anaplastic​ medulloblastoma

Medulloblastoma with extensive nodularity