Cancer of unknown primary site…. Never heard of it until my mum was diagnosed having it last year around August. We have been asked by our lecturers to focus on the commonest diseases 1st because “Common thing is common.” We are not encouraged to pay attention on the rare diseases. But as a student, usually we tend to memorize the rare thing better compare to the commonest thing. The same thing goes to me. It is my fate to face this rare disease during the earliest exposure to clinical practice. And, having it on my own mum increases my curiosity even more altough it is rare.

My mum was diagnosed with sickle cell anaemia since her teenager. But she never gone thru any blood transfusion before since her anaemia was not too severe in which her Hb level range between 8 – 11 g/dL and she was asymptomatic. In November 2005 during fasting month, she went thru her 1st blood transfusion when her Hb level was dropped to 6.0g/dL and she was pregnant during that time. During the procedure, she developed urticaria as a result of transfusion reaction. But the blood was only being stopped after half of it was being transfused since no one told her to notify someone if she had any reaction. Besides, she thought it was a normal reaction for blood transfusion.

Two weeks later, she had miscarriage and had to undergone another blood transfusion as her Hb level was again dropped to 6.3g/dL. After the blood transfusion, both of her hands were swollen which was more prominent at the joint of the fingers. But, it was painless. She was unable to flex her finger due to the tense, thus unable to perform fine movements. Besides, there was a skin rash at the dorsum part of the fingers, predominantly at the knuckles of the fingers. The skin of the palms also became dry and rough and tips of the fingers became red. Hence, she was admitted to ward at HKT for further investigation. In the ward, she developed periorbital swelling of both of her eyes. Later, there were skin rash at the periorbital area and maxillary prominence of her face too.

Initially, she was suspected to develop sickle cell crisis. However, there was no hepatosplenomegaly and no other signs that suggested she was in crisis. More importantly, she was not in pain, thus unlikely in crisis. She was then investigated for rheumatoid arthritis and SLE as the presentation mimicked chronic tissue diseases. She was also investigated for gouty arthritis. Since all the investigations showed negative result, the doctor discharged her after 1 month- stayed in hospital. No referral letter or follow up was given to my mum eventhough she was discharged unwell and without any definite diagnosis. She was only being put on physiotherapy of her hands once a week.

At home, her condition became worsen. She was getting thinner and thinner. Her hair slowly lost causing her scalp to be visible. She also developed muscle pain at the thighs and calves. Because of it, she was unable to walk properly and her movement became limited. She had to sit on the chair to perform the prayer. She became so lethargic and always sleeping. Besides, she also noticed a lump at the anterior triangle of her neck which I suspected to be thyroid in origin. Concerned about her health, I advised her to go to hospital for several times but she refused as she already became frustrated with the doctor whom did not put her on follow up or referred her.

In July 2006, I brought her to HTAA after talking with my lecturer about her condition. On examination, she was found to be cachexic and there was a presence of alopecia and proximal myopathy of lower limbs. Besides, the doctor found right thyroid enlargement and large hepatomegaly. The liver was firm and had smooth surface. Thus, she was admitted to the ward for further investigations.

The doctor who is my lecturer told me that he would like to rule out CTD 1st before investigated for other diseases like malignancies. Based on skin rash at the face which resembles butterfly rash and alopecia, SLE became the provisional diagnosis. Rheumatoid arthritis and gouty arthritis have became the differential diagnosis as she presented with swollen hands which was more prominent at the joint and limitation of finger’s movement . The redness at the fingertips has been suspected to be due to vasculitis, therefore Raynaud’s phenomenon or cryoglobulinemia also need to be excluded. Several blood tests were ordered to rule out all the differential diagnosis and all came back to be normal, same as when she was in HKT.

Otherwise, blood test for Hb electrophoresis which was sent to IMR showing 47% of HbS confirmed the presence of sickle cell anaemia. Ultrasound of thyroid showed cystic degeneration and FNAC that was done confirmed the finding. To be more accurate, the FNAC was repeated with the ultrasound guided. Yet, it gave the same result.

Since she had hepatomegaly, she was scheduled for ultrasound and the result showed multiple heterogenous lesions suggestive of liver metastasis. Further CT scan of abdomen also gave the same result. Thus, the doctor called me to discuss about me the finding. Before seeing him, while assessing her file, I already saw those findings. Reading those report, I strongly wished for the report to be wrong and it’s not what I’m thinking of. Once the doctor breaks the news to me, my heart felt like it want to burst. The only thing that came into my mind during that time was to be away from there as soon as possible before my tears came out. The doctor told me that he strongly felt that it was not SLE from the begining since the onset of SLE is usually during adolescent, but he didn’t expect it was something that was more sinister than it and he asked me to be prepared for whatever possibilities.

With those findings at the liver, the doctor started work out to find the primary site of the cancer. Whole body scans such as CT scan of neck, thorax and abdomen were ordered in order to find the primary site as well as to know the spread of the disease. CT scan of neck showed right solitary thyroid nodule and there was no cervical or supraclavicular lyphadenopathy. CT scan of thorax showed bilateral lower lobes lungs fibrosis with small subpleural nodules. There was no hilar or mediastinal lymph nodes enlargement as well as no pleural effusion noted. Surprisingly, CT scan of abdomen was unable to determine the primary lesion in the abdomen and pelvis. There was no para-aortic lymphadenopathy. However, the appearance of bulky uterus required further gynaecological assessment. Gynaecological review however unable to find any abnormalities that can suggest gynaecological malignancies.

Mammogram can’t be done as there was no breast fat due to wasting. Ultrasound of the breast was done as a replacement and it showed no lump or any abnormalities.

In addition, several blood tests for serum tumour markers such as CEA, CA 125, CA 19.9 and AFP were also sent to get the ideas about the origin of the cancer cell. CA 125, CA 19.9 and AFP were within normal range. On the other hand, CEA was very high, up to > 5000 suggestive of GIT or reproductive tract in origin.

Along with that, she was also being reviewed by dermatologist during her period of stay in the hospital for hyperpigmentation of the knuckles of her hands and her face. The skin problem was diagnosed as dermatitis while the proximal myopathy occurred as a result of myositis. Based on the presentation, it was believed that she developed dermatomyositis as a result of paraneoplastic syndrome secondary to the malignancy. From my reading, it is common for the cancer to be accompanied by paraneoplastic syndrome. And, for dermatomyositis, it commonly occurs in stomach cancer. No skin or muscle biopsy was done as it will not be so helpful in term of management.

Due to high CEA, she was arranged for OGDS and colonoscopy as the primary site might be in GI tract. Again, suprisingly, OGDS only showed pangastritis while colonoscopy was inconclusive because of poor bowel preparation. However, no obvious obstructed lesion was seen. She was then scheduled for barium enema to get better view of the GI tract as barium enema is more sensitive in detecting small lesion. But still, no lesion was found. Extensive investigations have been done, yet no primary site has been detected. The doctor came to the dead end, thus finally decided to go for the last option which was liver biopsy. She was however discharged after being in the ward for about one month to take a rest at home before come back again for the biopsy.

She was admitted again one week later somewhere around August for the liver biopsy. It was not done earlier due to risk of bleeding since her liver was not function normally and risk of seedling of cancer cell through the biopsy tract. Liver biopsy was done by the consultant radiologist and she was advised not to move at least for 6 hours after the procedure. BP and site of the biopsies were monitored every hour for signs of bleeding and shock. HPE result confirmed the presence of cancer cell which was adenocarcinoma in origin.

With that, we all agreed to stop investigating her as she already gone through extensive investigations, thus making the final diagnosis as liver metastasis of adenocarcinoma of unknown primary site with dermatomyositis. It was a standard protocol to inform your patient when the diagnosis was confirmed. When the doctor breaks the news to her, she just kept silent. Knowing she already knew the news, I didn’t know how to face her, how should I react. She told me that she already expect the bad news because the doctor always called me and discussed about her disease away from her as if the doctor wanted to hide something from her. So, it was like she already a bit of prepared when the doctor told her the news. She was then discharged before coming again for the treatment.

Since the primary site was unknown, it was a bit difficult to manage. The attending doctor sat together with a lot of specialists including oncologist from HKL just to discuss regarding the treatment that she should receive and how to manage her. From the discussion, they all agreed to start the chemotherapy. Based on high CEA and since the liver is the most common metastatic site for GIT malignancy, they agreed to put her on Mayo’s regime, the chemotherapeutic regime for colorectal cancer. It consists of 5-FU and folinic acid. The doctor told me to bear in mind not to put so much hope on the chemotherapy since it was just to prolong her life, not for the cure.

In September 2006, she started her 1st chemotherapy. Initially she was started with oral chemotherapy as the doctor afraid she would not able to sustain the side effect of the chemotherapy because she was too weak and cachexic. But when she seem to be okay with the chemotherapy, the doctor converted into intravenous chemotherapy as it is more effective. The agents were administered continuously for 5 days. Normal saline was administered before and after the chemotherapy to avoid the risk of dehydration as the chemotherapeutic agent is cytotoxic. Luckily, she didn’t develop any side effect of the chemotherapy such as fever, vomiting, diarrhea, etc. Since then, she was admitted monthly for the chemotherapy. She was also given Prednisolone as a treatment for the myositis and steroid cream for the dermatitis.

During her 3rd cycle of chemotherapy, the doctor repeated the abdominal ultrasound to see the liver response toward the chemotherapy. Unfortunately, not only the size of the lesions were getting bigger, the number of the lesions were also increased. It can be seen through physical examination in which her liver getting bigger, firmer and became more lobulated. However, she claimed that she was getting better. And, it was true actually. Clinically she really looked much better. She can move better than before. But, it was not the effect of the chemotherapy, it was a result of the Prednisolone. On the other hand, the serum tumour maker, CEA did reduce to >1000.

During her admission for her 4th cycle of chemotherapy, she complained of passing mucus and blood per rectally. Thus, the doctor repeated the colonoscopy and found a fungating mass at the rectosigmoid junction, 20 cm from the anus. The doctor didn’t proceed further as the mass obstructing 1/3 of the lumen as there was a risk of bleeding if trauma happens.

With the finding, she was referred to surgical department as the colon was suspected to be the primary site. The biopsy result from the colonoscopy however was inconclusive as it only showed severe dysplastic gland. The surgeon decided not to repeat the biopsy because it would not going to change the management as the chemotherapy agents that she received was the regime for colorectal cancer already.

She was then scheduled for CT scan of abdomen to know the extent of the disease. Confusingly, no mass can be located in the bowel from the scan. The liver was very big, pushing the right kidney downward. There was a presence of minimal ascites. However, there was no signs and symptoms of CLD, not even a jaundice and the liver enzymes were within normal range.

In January 2007, she was admitted again for her 5th cycle of chemotherapy. On the 3rd day of the cycle, she developed Herpes Zoster skin infection at the abdomen, area below the right subcostal margin anteriorly and posteriorly. It was recurrent infection as she already had the infection once during her adolescent. It might be occured as a result of her immunocompromised state secondary to the chemotherapy. Due to the infection, the chemotherapy was stopped as it may worsen her condition. After stayed in the ward for about two weeks, she was discharged without completed her 5th cycle of chemotherapy. She was asked to come again to the clinic two weeks later for the review of her condition as well as the skin infection.

During her review in February 2007, the doctor advised her to stop the chemotherapy since it was not effective. The liver showed no response to the treatment at all. Only a small portion of normal liver cell left. If she proceeds with the chemotherapy, the doctor afraid that the chemotherapeutic agent which is cytotoxic might destroy the normal cells too, hence making the progression of the disease become faster. However, the doctor did give the choice to her if she wants to finish the chemotherapy until the 6th cycle. After giving a deep thought about it, finally my mum decided to stop the chemotherapy. The Prednisolone was also stopped after being tapper down previously as the risk outweigh the benefits if it was prescribed for long term.

Currently, she is resting at my aunty’s house because nobody could take care of her food since she cannot eat rice anymore. My dad doesn’t have the time for it since he has to take care of my younger brothers and sister. Besides, he is too not very well. Therefore, the best solution is for my mum to stay with my aunt and my grandma. She would only come back home if we all come back for holiday.