Overweight. Sideropenic anemia. Right ovarian cyst (8 cm). Sacrococcygeal cyst. Intolerance to paracetamol.

Case history:

· Onset of painful swelling in left supraclavicular area with no other symptoms. Therefore, an ultrasound of the neck was carried out, in which the lymph node packet in the left supraclavicular region was emphasized. Augmentin was administered for 1 week with no benefit. In addition, during the weeks preceding the onset of the firm dorsal subcutaneous swelling, which was not investigated, there was secretion from a left submental nevus that spontaneously resolved, after which a left supraclavicular nevus appeared.

· From --- to --- -> Admission to the Hematology Department of a Clinical Institute for a lymph node biopsy and histology test: “Lymph node fragments at localization site of malignant epitheliomorph neoplasia consisting of large macronucleolated elements with large cytoplasm and having the following immunophenotype profile: S-100(+), HMB45(+), melan-A (rare + cells), CLA(-), CKpool(-), EMA(-), ALK(-), PLAP(-), Synaptophysin (rare + cells), CD30(-), CD56(-).” The results indicate lymph node melanoma metastases.

· CAT scan of brain, neck, chest and abdomen with contrast medium: “In left area of neck, lymphadenopathic mass from level 4 to the axillary glands; the anteroposterior and laterolateral diameters of the initial lymphadenopathic conglomerate are 7 cm and 3.5 cm; in the left axillary region there are multiple lymphadenomegalies, the maximum being approximately 25 mm; the lymph nodes described in the laterocervical-retroclavicular and left axillary area are compressing the venous axes, although without causing thrombotic phenomena currently; solid tissue of pyramidal appearance in anterosuperior mediastinum related to thymic residue.” Total-body PET: “Various hyperfixation areas attributable to adenopathies, partially confluent in the conglomerate, in the laterocervical, subclavicular and left axillary regions, as well as left subscapular and bilateral intercostal areas, with an area of intense fixation of neoplastic significance (SUV max 14.1 diameter 33 mm) in cutaneous and subcutaneous regions in left paramedian area of trunk.” Oncology visit: “Chemotherapy with Cisplatin, Vinblastin and Decarbazine (CVD regimen) is felt to be indicated, in combination with immunotherapy with Interferon alpha-2b, three million units three times a week subcutaneously. Indication of prophylactic antithrombotic therapy should also be evaluated for the compression of venous axes in the neck and left axillary region.”

· Neck and subcutaneous ultrasound: “The clinically-palpable swelling in the left dorsal region appears as a large nodular distinctly hypoechogenic formation, with regular edges and a few small vascular poles of its own, which extends approximately 60 mm along the muscle plane and has a thickness of approximately 38 mm, attributable to an heteroproductive formation. In the inferior laterocervical and right supraclavicular region, there are a few small, round hypoechogenic lymph nodes of 8 mm max. of pathological appearance; in the left laterocervical and supraclavicular region, there is an adenopathic mass of pathological appearance, in particular a pathological lymph node packet that extends approximately 75 mm”; Cardiology visit: “Within normal limits”; ENT visit: “Within normal limits. In particular, there are no lesions in the ENT area relating to the primary T.”

· 11/7-28/2006 “Two cycles of chemotherapy with cisplatin, decarbazine, vinblastin/CVD) in combination with interferon alpha-2b, 3 million units subcutaneously three times a week, with noted clinical and ultrasound progression of the disease (appearance in left suprascapular region of a new, firm/elastic swelling of approximately 5 x 4 cm, with ill-defined margins, painful and painful to touch, another very small-sized, non-painful hard swelling on right arm). Therefore, chemotherapy was stopped, immunotherapy was continued and a review of the patient’s whole condition was planned. Therapy was started, taking into account the patient’s radiological information and the risk of thrombosis, in addition to the aggressiveness of the current therapy, the underlying condition and the family history. Prophylactic thromboembolic therapy was prescribed with nadroparin calcium 7600 IU a day subcutaneously; 1 vial subcutaneously a day. As progression of the disease was observed following the second cycle of therapy, and due to the patient experiencing pain extending from the neck to the interscapular area, analgesic therapy was prescribed with tramadol, which was not well tolerated and was of no benefit.”

· Total-body CAT scan: “Appearance of some nodular pulmonary formations bilaterally, ranging in size from a few millimeters to 1 cm, and related to secondary lesions, the largest of which in the right apical region of approximately 9 mm; large lymphadenopathies in left axillary region, the largest of which having a necrotic nucleus of approximately 4 cm; solid tissue of secondary significance in left paravertebral muscles, medially to the homolateral scapula profile, of approximately 5.5 cm x 4 cm; solid tissue of pathological significance in the more caudal region along the left paravertebral muscles, having a maximum diameter of approximately 5 cm and extending craniocaudally approximately 6 cm. Brain CAT scan with contrast medium: negative.”

· Approx. 2 week periodChemotherapy with fotemustine 100 mg/sq. m. a week to a total of 3 administrations in total.

On ---, the patient was admitted to the --- Clinical Institute of Oncology for significant asthenia, as well as anemia and significant thrombocytopenia observed in the patient’s hemochrome in the Emergency Room, for which support therapy was prescribed.

Admission tests:

GB 1200, Hb 6.8, PLT 5000

Discharge tests:

Hb 9, PLT 60000, remaining values within normal limits.

In particular, the patient had the following therapies:

Blood transfusion of red cell concentrate 2 IU.

Platelet pool transfusion.

Blood transfusion of red cell concentrate 2 IU.

The results of the chest and neck CAT scan of --- were as follows: The results were compared with those of ---. “Presence of adenopathies in left supraclavicular region with maximum diameters of 47 mm x 34 mm. The known focal lesion located in the left cranial paravertebral soft tissue medially to the homolateral scapular ala currently has transverse axes of 50 x 65 mm and appears to be increasing in size. The second more caudal formation in the left paravertebral region also appears to be increasing in size, having transverse axes of 66 mm. The right adenopathy is increasing in size, while the formation on the left which was previously bigger has decreased in diameter. As regards the pulmonary parenchyma, there has been a progression in terms of size and number of the secondary bilateral localizations, the largest of which is currently in the right superior apical lobe and has an axis of 11 mm. In addition, there is left pleural effusion. Uncertain osteolytic abnormalities in cervicodorsal metamers with lytic characteristics or invasion of the spinal canal.”

This admission can be summarized as follows:

“The patient was admitted for medullary pancytopenia. On ---, a blood transfusion of red cell concentrate 2 IU and 1 platelet pool was carried out; during the patient’s hospitalization, another blood transfusion of red cell concentrate was carried out on --- (2 IU); in addition, analgesic therapy was prescribed, which provided good control of the patient’s pain.. However, the patient has difficulty walking and requires orthopedic support, such as an orthopedic bed with an anti-bedsore mattress and a wheelchair. The follow-up CAT scan carried out during the patient’s hospitalization showed a progression of the lymph node and left paravertebral condition, which was also observed clinically. Given the previous chemotherapy cycles, as well as the progression of the condition, continuation of specific chemotherapy is not indicated. In the event of confirmed progressive normalization of hemochrome values, the patient should participate in a clinical study protocol using radioactive marked antibodies (at the ---).

During this hospitalization, a colleague from the ---in --- was contacted about the possibility of radioreceptive therapy. In the event of full medullary recovery in future, specific immunotherapy may also be considered at the --- hospital.”

 

 

 

Questions:

1) Are there any other effective therapies in addition to the ones that have already been carried out?

2) Are there any centres of excellence that are able to handle this case urgently?

3) What is the prognosis?

 

 

 

Medical Report:

 

Patient- 20 years old.

 

Dear Medical Opinion,

Thank you for a request for a second opinion on this patient with progressive malignant melanoma. I reviewed the medical notes that you provided and offer you the following opinion for consideration.

 

Based on the immunophenotype data (S-100+, HMB 45+, melan A [rare cell]) I agree that the diagnosis is malignant melanoma with an unknown origin of the primary site. Using the TNM classification system, she has stage IV disease with involvement of several regional and distal lymph node clusters as well as subcutaneous and soft tissue metastes.

 

Between --- and ---, she received 2 cycles of chemo therapy consisting of cistaplin, dacarbazine and vinblastine in combination with interferon Alpha 2b, SC tiw. Despite this, the disease progressed, the chemotherapy was stopped but the interferon was continued. Between --- and --- (two weeks), chemotherapy with fotomustine was administered once weekly for 3 cycles but the disease continued to progress.

 

The central questions at the point are:

1. What is the prognosis?

2. Are there other effective treatments?

3. Who are the experts in Europe?

 

Since decarbazine has been considered for many years to be the reference single agent for metastic melanoma, the failure of this patient to respond to this treatment equates to a very poor prognosis. Fotemustine may be even more effective than decarbazine (J Clin Onc 2004: 22 1118-1125), yet no response was seen there either. It is clear that the patient´s melanoma is refractory to standard chemotherapy and she should be enrolled in a clinical trial.

 

First, though, the following are treatment trial designs that I would not recommend. There have been about 30 randomized phase three trials conducted over the past 20 years or so to investigate the impact of polychemotherapy, the addition of low and high dose IL-2, tamoxifen, low and high dose interferon alpha, GM-CSF, and any combination of these. The evidence shows that these combinations increase toxicity but with no improvement in survival. IL-2, in particular has been a big disappointment. The absence of phase III data showing benefit of IL-2 at any dose in metastic melanoma prevented its approval in Europe. Vaccine therapy has similarly had no impact on survival because of very low response rates.

 

What I would recommend is that the patient seek enrollment in any one of the three following targeted therapy products that has caused considerable excitement among melanoma experts. My first choice is anti- CTLA-4 antibodies (J Immunother 2006; 29;455-463) , but sorafenib (Clin Cancer Res 2007; 13; 1801-1809) and oblimersen (J Clin Onc 2006; 24;4738-4745) also exhibit great potential. There may be other products that with potential that may be on trial in Europe. The following distinguished melanoma experts will provide direction.

 

The patient should consult with one or all of the following attached to see if she is eligible for a clinical trial.

I trust that this has been helpful. I wish the patient the very best in her quest for effective therapy.

Sincerely,

-----, MD, FRCPC, FAAP

Professor ------