Cancer Treatment Today » Concepts in Oncology

Double Hit Lymphoma

M Levin, MD — Wed, 19 Sep 2012 01:08:21 +0000

Double – hit (DH) lymphomas are a recently discovered subtype of lymphoma that is defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint, for instance a t(14;18)(q32;q21), involving BCL2. In the 2008 WHO classification, they are classified as “B cell lymphoma unclassifiable with features intermediate between Diffuse Large Cell Lymphoma(DLBCL) and Brkitt’s Lymphoma(BL)”. Thus, it is somewhere between intermediate and highly aggressive lymphomas in how it behaves.

In some ways it is similar to Burkitt’s; however, while the diagnosis of Burkitt lymphoma (BL) is generally straightforward, these lymphomas tend to have atypical morphologic and/or immunophenotypic features that overlap with other types of high-grade B-cell lymphoma, particularly diffuse large B-cell lymphoma (DLBCL). They often have an extremely poor prognosis, with a median survival of 6 or so months and represent an entity distinct from both Burkitt’s Lymphoma and DLBCL.

Unfortunately, it is no known how to treat double-hit lymphomas. The prevailing paradigm among oncologists has been to treat more aggressive cancer more aggressively but it is now being questioned. While it is tempting after initial chemotherapy to consolidate with high dose therapy and transplantation, the entity is too new to have accumulated significant published information on response to therapy and role of transplantation. NCCN currently recommends for DLBCL: ”consider high dose therapy Category 2B for complete and incomplete responders in high risk patients”. That seems to be a reasonable approach also to a Double Hit Lymphoma at this time.

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Is granular cell tumor cancer?

M Levin, MD — Tue, 18 Sep 2012 20:43:08 +0000

Granular Cell Tumors are rare with only about 200 cases reported, some half of them in the mouth and neck area. Whether it is cancer or not has been controversial but it has recently been shown to be of early neural tissue origin(Rejas et al). However, some granular tumors behave benignly, meaning that they don’t invade and spread, and others can be very aggressive and the older literature contains many reports contrasting “malignant” and “benign” granulosa cell tumors. Only 2% of granular cell tumors behave like cancers, but the fact that some do confuses this issue. NCI defines “cancer” as a term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems, what si called metastasizing. Great majority of granular cell tumors do not have these characteristics, and they should not be considered to be cancer.

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Is Langherhan’s Hystiocytosis a cancer?

M Levin, MD — Tue, 18 Sep 2012 20:35:59 +0000

The pathogenesis of Langerhans cell histiocytosis (LCH) is a mater of debate. LCH is a rare disease that can invade tissues and spread but otherwise looks like a reactive process. There is ongoing controversy as whether it is a cancer. Supporting the reactive nature of LCH is its propensity for spontaneous remissions, the extensive secretion of multiple cytokines by dendritic cells and bystander-cells (a phenomenon known as cytokine storm), favorable prognosis and relatively good survival rate in patients without organ dysfunction or organ involvement.

On the other hand, the pathologic features of infiltration of organs by monoclonal population of pathologic cells, and the successful treatment of subset of disseminated disease using chemotherapy argue that it is neoplastic process. In addition, X chromosome–linked DNA probes appear to demonstrate a degree of monoclonality. Monoclonality is an important attribute of cancer but it does not prove that a proliferative process is neoplastic. Specific and unique cytogenetic or genomic abnormalities would also be required to demonstrate convincingly that LCH is a malignancy.

Activating mutation of a protooncogen in the Raf family, the BRAF gene, was recently detected in 35 of 61 (57%) LCH biopsy samples with mutations being more common in patients younger than 10 years (76%) than in patients aged 10 years and older (44%) and two other studies showed a similar result. Presence of this activating mutation could support the notion that LCH s a precancerous condition or a myelodysplastic disorder.

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Cryoablation for kidney cancer

M Levin, MD — Wed, 12 Sep 2012 21:45:59 +0000

Cryoablation is not well supported by the medical literature for renal cell cancer. There are mostly case reports and series, although some of them are large and there are no comparative trials. The procedure has some theoretical disadvantages. For one, it leaves no pathology, so that prognostication becomes difficult. Other limitations of percutaneous cryoablation include the inability to control hemorrhage without intra-arterial access and a lack of long-term follow-up data. Perioperative complications and renal functional outcomes of laparoscopic cryoablation and open partial nephrectomy are similar; however, laparoscopic cryoablation confers a substantially higher local recurrence risk of about 15% after 3 years. There are no formal guidelines but some experts believe that laparoscopic renal cryoablation should be reserved for high risk patients with decreased life expectancy.

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NK cells in medicine

M Levin, MD — Wed, 20 Jun 2012 18:39:56 +0000

Natural killer (NK) cells, a type of T lymphocyte cell, are major actors of the body’s immune responses against viruses, bacteria, parasites, and other mediators of pathology such as malignant transformation. These cells are also directly implicated in the link between by preexistent body’s own and adaptive, newly developed immunity, shaping T-cell responses. It is now obvious that manipulation of this lymphocyte subset could be the basis of new therapeutic approaches for cancer and/or pathogen-driven pathology. There is an interest in these cells in reproductive medicine, which is not a focus of our discussion.

There is some older evidence that loss of NK activity as an indicator of relapse in acute leukemia. These studies concluded that there was a marked reduction in NK activity in patients with relapsed leukemia when compared with healthy controls, and that NK activity substantially improved in complete remission. What this means for clinical medicine is not clear. Patients with CD20+ follicular lymphoma fared better when treated with the humanized anti-CD20 monoclonal antibody rituximab if their NK cell driven responses worked better than ones who did not; however, therapeutic attempts to use this information to develop novel approaches have failed.

The NK field is currently in the stage still of gathering information and conceptualizing it into a set of insights that can then be refined and applied. It is not ready for routine clinical use.

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