I can never forget this case. The day when I first saw Jerome*. He struck me as the nicest bloke you would ever meet - a laid-back gentleman sporting a polo shirt with spectacles resting on his high nasal ridge. He was transferred to the general medical ward yesterday, with hospitalisation being an issue of reassurance. In the 71 years of his life, never had he been so preoccupied with his tummy. For the past few months, he presented with various gastric symptoms, including belching, tummy pain (over the left upper quadrant) and early fullness in eating. However, he was most concerned about the firm mass that grew slowly but surely on the left side of his tummy. At first, it was a mere, unnoticeable bump. Now, coated by his polo shirt, there emerged a distinct large mass which spread from the top left-hand corner of his abdomen to his belly button. Another worry, more on our side, was the presence of a string of non-specific, constitutional symptoms. While Jerome insisted that they were more associated with ageing and a busy post-retirement life, we weren't so sure, chiefly because they might mean something sinister. He started to feel tired, lost a great deal of weight and did not want to eat much (these might go back to the stomach problem). He also got night sweats and felt a simmering wave of heat pulsating through his body. It might be indicative of a low-grade fever, typical in chronic illnesses such as cancer and autoimmune diseases. Just before the physical exam, he slipped in one seemingly trivial (but turned out to be vital) symptom: he couldn't breathe well. At this point, we're narrowing down to things typically found in that part of the tummy - the stomach, the spleen (which is housed under the ribcage, over ribs 9-11: Traube's Space), the pancreas and the small bowel. A creative colleague suggested a ribcage tumour but we're not ready to take it that far (osteosarcomas remain rare).
Location of the Spleen (extracted from Mayo Clinic)
I was thrilled to be able to perform the abdominal examination. When we talk about the 'abdominal examination', it sounds much more focused than it is. However, one of my tutors has once said that everything starts with a general examination - meaning an initial assessment of the whole body. A good clinician always looks for signs and clues around the body before zooming in. It's like using a microscope - we look at the large field of cells, before identifying a section of interest and zooming in. Doing things this way reduces the risk of error. Sometimes, just like this case, maintaining a narrow view of focus can render us ignorant of the myriads of possibilities available. In a general exam, we go from top to bottom. Literally. Starting from the eyes, we look for signs such as pallor (indicative of anaemia - deficiency in red blood cells) and jaundice (yellowing of the sclera, which is usually the 'whites' of the eye; this is related to a broad range of disorders, mostly concerning the liver and gallbladder, both located in the right upper quadrant). We also look for 'funny' signs such as the Kayser-Fleischer Ring, which is indicative of Wilson's Disease - a copper-storage disorder concerning the liver. [2] Then, we examine the chest wall and hands. They are particularly important for liver diseases, but can occasionally shed an inkling to a pathology at an alternative location. Sometimes, the eagle-eyed can spot a small dash of red over the chest wall. Leaning closer, this dot of red looks like the old flag of the Japanese Empire: a central, red dot with spiking, crimson processes radiating from the core. We call it a spider angioma, which is closely correlated with chronic liver disease (high oestrogen). [3] Over the fingers, a very non-specific sign can sometimes be perceived: the thickening of the tissue at the root of the nail. We call it finger clubbing. Dedicated gastroenterologists and respiratory medicine specialists may tell you that they mean a lot. Well, let's just say that for me, I think it's better to rely on something more accurate (or in medical terms, more sensitive and specific).
Finger Clubbing Grade 4 - Hypertrophic Osteoarthropathy (extracted from http://medicalpicturesinfo.com/wp-content/uploads/2011/08/Clubbing-finger-2.jpg)
Moving on to the abdomen, that's where we get interesting. We always follow the same steps - observation (looking around for signs because once a clue is detected, it saves us a lot of work), palpation (touching, applying force to different structures), percussion (essentially doing an over-sophisticated knock in synthesis of a sound) and auscultation (having a listen; we do this for bowel sounds and any bulging sections of arteries, i.e. aneurysms). The most striking feature over Jerome's tummy is the mass over the left side of his body. He was rather slim, with little abdominal fat. I also saw bruises on the lower side of the belly - quite an unusual place to get hurt (What can it be?). He got pain over the left side in general, but was normal otherwise. His liver was slightly large, around 13 cm (the normal span should be 6 to 12 cm, depending on measurement).** [4] The edge is soft and smooth, thus normal. The last thing we want is a hard liver edge, which can mean liver cancer (here, there are two possibilities: it might be that the liver has a cancer of its own, making our job more difficult; or, if the mass on the left were a cancer on its own right, it might have spread to the liver, indicating worsened prognosis). I then moved on to the spleen, which became the primary suspicion of the investigative process. During physical examination, it is extremely hard, if not entirely impossible, to examine the pancreas since it is located deep in the abdomen.
The spleen is a magical organ. It performs various functions that don't match with the vibe of the rest of the abdomen. For the stomach and bowel, alongside the pancreas, they perform various digestive functions. The former two are part of the alimentary tract which refers to the pathway which the food bolus (the chunk of food swallowed) follows all the way from the mouth cavity to the anus. It is an elliptic organ which contains two major structures: (i) red pulp, and (ii) white pulp. It has to be noted that the red pulp accounts for about 80% of the entire organ mass. It is used for a variety of functions related to blood. Made up of venous sinuses and cords, it's used for filtering old and unwanted erythrocytes (red blood cells) and platelets. Moreover, there are macrophages available for devouring microbes which are already bound to antibodies (this is a process called phagocytosis, in which the mighty macrophage gobbles the germ up). The antibodies are bound to the microbe via 'opsonisation' (I know, chunky medical term alert; basically meaning 'I won't ever let you go, you're under arrest'). The white pulp is in the centre of the organ, surrounded by the red pulp. The white pulp is divided into three sections: (a) the lymphoid sheath which surrounds the perimeter of the arterioles [innermost part], (b) follicles (middle) and (c) the marginal zone (well, the outermost part). Here, (a) is densely populated with T Cells and macrophages. (b) is dominated by B Cells. (c) is conquered by massive hordes of macrophages. [5] With such vast functions, if the spleen gets so large, it is less likely to be an abdominal issue. Moreover, there remains a possibility that the stomach is only behaving in that way because the spleen is too large that it compresses against the stomach. In this case, patients like Jerome can experience epigastric symptoms like belching and post-prandial fullness (getting easily full after meals). It is very tricky since the spleen can get large in many circumstances. Here, we shan't be jump into any conclusions. That's why, if it's actually a spleen problem, we need to (a) determine the extent of the enlargement and (b) feel for its consistency. Also, it's best to check all the lymph nodes in the body since they are heavily related to the body's immune system, as with the spleen.
A cross-section of the spleen (here, we can see the red pulp and white pulp) (extracted from Nature Immunology; if you own the diagram, I apologise but I've lost the link so do contact me and I'll put your name here).
It's always tricky to examine the spleen. Some doctors might suggest examining the spleen with the patient lying stomach-up first, then pulling him to one's side to 'hook' the organ. Well, I'm in no position to voice my verbal disagreement but this approach is problematic. It causes unnecessary discomfort and frankly, other ways are already present to establish any undue enlargement of the structure. I would suggest looking at the method advocated by Stanford University, which entails a patient lying on his/her back first, followed by the clinician's palpation and percussion (in that sequence). During palpation, the clinician goes from the right lower quadrant (the exact spot remains argued - whether it's the right iliac fossa or slightly lateral to the right pubic tubercle) to the belly button, then all the way up to the 9th to 11th ribs where the spleen normally resides. It's sometimes hard to feel even an enlarged spleen. Stanford University recommends putting the tips of the fingers slightly underneath the ribs to tease out the origin of a mass. There are also ways to differentiate a mass of the spleen from a mass of the kidney (which can also be another tricky factor). Then, the knocking. What we usually do is to put the third finger of the left hand on the abdomen and start knocking the more distal (direction to nailbed) part of it with the tip of the third finger of the right hand. This knocking follows the same pattern. It is important for us to use percussion, as a more sensitive technique, to determine the extent of the enlargement. If you haven't felt the consistency already in palpation, percussion also returns us with valuable information since air in the bowel returns a 'resonant' note, which is higher-pitched than spleen tissue, which returns a 'dull' note (lower-pitched)***. There is a shortcut to all this - there is a point between the mid-clavicular line and the costal margin. It's called the Castell's Spot. At this point, we ask the patient to breathe out completely prior to starting. Breathe in, I said. If the spleen were normal, the note would remain resonant throughout. If it were enlarged, it would go from resonant (due to the stomach) to dull. Sometimes, if the splenomegaly were gross (not the lay meaning - in medicine, it means 'very'), then it would be dull without having the patient breathing in. Jerome's spleen is confirmed to be enlarged - it left the confines between the 9th and 11th ribs and travelled all the way to the belly button and the left lower quadrant. It remains firm in consistency.
CT Scan - Gross Splenomegaly (remember, it's on the left; the right shows the liver) (extracted from https://i.pinimg.com/736x/8b/1d/4f/8b1d4f4efe2a7ea21e474397d91d473c.jpg)
Okay, at this point, we're worried about a lot of things. We also take into account our findings regarding the liver. Alright, it's only 13 centimetres in span - so not as enlarged as we would've hoped. Moreover, it's encouraging to note that the liver edge is smooth - not indicative of cancer or anything malicious. We also cannot identify, at the first instance, any lymph node enlargement. Lymph node enlargement doesn't tell us much, except that it flags up infection, autoimmunity, leukaemia and lymphoma (respectively: cancer of blood and cancer of lymph nodes). Infections are unlikely since Jerome's vital signs are fine and he is not feverish. But then, even an infection rarely results in such gross enlargement of the spleen. Autoimmune diseases are also ruled out because of incompatible clinical history and symptoms. They are more common in middle-aged female patients with positive family history and systemic symptoms (this is probably due to the high concentrations of oestrogen in the female body, since oestrogen augments the immune system). What is making his spleen so large?
We proceeded with investigations. Not to bore you with so much detail, we're totally shocked when we got the blood results back: (1) low red blood cells, and (2) low platelets. The low amount of red blood cells circulating in his body might explain why he couldn't breathe well and was always tired. The low amount of circulating platelets could contribute to low clotting function, leading to the appearance of bruises in unconventional places - meaning places where trauma would be less likely. In children, of course, we would then think about child abuse instead of jump straight to the belief of clotting dysfunction. We did other tests, involving the bone marrow and further examination of blood cells. The results were astonishing - every time we see a rare disease pop up, it's like all the hours of running up and down are worth it. Well, this and the smiles of patients who recovered from their illnesses. The B Cells essentially looked like this:
This was a peripheral blood smear showing 'hairy cells' - B cells (under the broad umbrella of lymphocytes) with numerous spiky processes radiating from the centre. (not from the patient- source: Wikimedia Commons)
The bone marrow test didn't proceed as well as we'd hoped. Originally, we wanted to get some fluid out of the bone marrow. That failed. Nothing came out. We then did a biopsy and performed additional biochemical tests. Just for the sake of completeness, no infection or autoimmunity was identified (negative cultures; negative results for ELISA for autoimmune antibodies, such as Anti-nuclear antibodies).
The diagnosis was confirmed - 'Hairy Cell Leukaemia'.
No disease name had ever made me laugh like that. I don't know - perhaps my naivety seeps into moments of seriousness without my realising. Hairy Cell Leukaemia is a type of blood cancer which features abnormalities of the B cells. This is a relatively rare disease, which accounts for 2% of all cases of leukaemia. There is around 1 case in 100,000 people per year. [7] It is a burdensome disease, since relapse and secondary malignancies are common. The median overall survival is around 27 years after treatment per protocol, where the median overall survival without relapse (having another episode of hairy cell leukaemia) is 11 years. The cumulative relapse incidence rate is found to be 39%. However, prognosis remains good, provided that the patient doesn't mind being subjected to long-term follow-up. [8] In general, purine analogues are used for treatment. Drugs implicated include cladribine and pentostatin. Moreover, for patients with relapsing disease, rituximab, a synthesised antibody against B Cells (CD20, the B Cell antigen, to be exact), can be used in conjunction. Although the splenomegaly is worrying, only in rare circumstances shall a splenectomy (Resection of the spleen) be necessary. We don't usually want to subject the patient to extra risks during and after surgery, especially when splenectomy leads to gross immunodeficiency (vaccines are administered straight afterwards). Also, splenectomy is only warranted in urgent situations such as splenic rupture and massive splenomegaly leading to severe mass effect. [9]
I think, suffice to say, whenever an old man comes to the clinic with epigastric symptoms and a left-sided tummy mass, never forget the blood!
*Again, Jerome is a fake name. This is to protect patient's anonymity. Moreover, consent has been obtained for the purposes of this case report. No patient particulars are relayed. Only medical facts are stated and iterated throughout this article.
**This is the proper way of doing it - palpating the liver for any nodules and masses, then moving on to percussion to determine the exact liver span. However, speaking on behalf of most bumblebees, we don't bring measuring tapes to the wards. Some don't even have stethoscopes and have to borrow others' so...What we do is to palpate from the right lower quadrant all the way up to the edge of the ribcage (also known as the costal margin, where costal = X coastal; it means rib in a posh way) and if we can't feel anything dull throughout, we just take it as normal. Some papers might suggest that a liver edge felt up to 2 cm beneath the costal margin still counts as normal:
See Gilbert VE. Detection of the liver below the costal margin: comparative value of palpation, light percussion, and auscultatory percussion. (1994). Southern Medical Journal. 87(2):182-186. DOI: 10.1097/00007611-199402000-00006.
Also, it's actually quite hard to feel anything below the costal margin- I mean, we bumblebees are still biologically human and we have limited sensory capabilities.
See: Ralphs DNL, Venn G, Khan O, Palmer JG, Cameron DE and Hobsley M. (1983). Is the undeniably palpable liver ever 'normal'? Annals of the Royal College of Surgeons of England. 65(3), 159-160.
***There are more ambiguous labels such as 'stony dull' referring to pleural effusion- however, it's very hard to tell. Many doctors I've spoken with say that it's best to say it's dull and confirm it with an X-Ray.
[1] Parry‐Jones N, Joshi A, Forconi F, Dearden C. (2020). Guideline for diagnosis and management of hairy cell leukaemia (HCL) and hairy cell variant (HCL‐V). British Journal of Haematology.
[2] Low QJ, Siaw C, Lee RA, Cheo SW. (2020). Kayser–Fleischer rings and Wilson’s disease, QJM: An International Journal of Medicine, 113(9), 693-694.
[3] Detry O, De Roover A. (2009). Images in clinical medicine. Spider angiomas. N Engl J Med. 360(3):280.
[4] Liver Exam. Stanford Medicine 25. (2020). Retrieved 19 November 2020, from https://stanfordmedicine25.stanford.edu/the25/liver.html#:~:text=Liver%20span%3A%20commonly%20clinically%20under,line%3A%20normally%204%2D8cm.
[5] Paxton S, Knibbs A, & Peckham M. (2020). The Leeds Histology Guide. University of Leeds. Retrieved 19 November 2020, from https://www.histology.leeds.ac.uk/lymphoid/lymph_spleen.php.
[6] Spleen Exam. Stanford Medicine 25. (2020). Retrieved 19 November 2020, from https://stanfordmedicine25.stanford.edu/the25/spleen.html.
[7] Tadmor T, Polliack A. (2015). Epidemiology and environmental risk in hairy cell leukemia. Best Practice & Research Clinical Haematology. 28(4), 175-179.
[8] Paillassa J, Cornet E, Noel S, et al. (2020). Analysis of a cohort of 279 patients with hairy-cell leukemia (HCL): 10 years of follow-up. Blood Cancer Journal. 10, 62.
[9] Sarid N, Ahmad HN, Wotherspoon A, Dearden CE, Else M and Catovsky D. (2015), An unusual indication for splenectomy in hairy cell leukaemia: a report of three cases with persistent splenomegaly after chemoimmunotherapy. Br J Haematol, 171: 784-787. https://doi.org/10.1111/bjh.13767.
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