The Simplest Explanation is Usually the Correct One (A Medical Case in Which the “Ockham’s Razor” was Fulfilled)

A 77-year-old female patient was admitted at the Internal Medicine Unit for symptoms of fever lasting for about a week despite of an antibiotic treatment with levofloxacin (maximum body temperature of about 38 °C), asthenia, night sweats and itching in the upper and lower limbs and in the abdomen. She was affected by chronic ischemic heart disease, arterial hypertension, carotid and lower limbs of arteriopathy, chronic vascular leukoencephalopathy and mild depression. She was treated with an angiotensin converting enzyme (ACE) inhibitor, beta-blocker (carvedilol), acetylsalicylic acid, atorvastatin, torsemide and lansoprazole. On first physical examination, the patient showed mildly rough respiratory sounds, a moderate (2/6) aortic systolic murmur and enlarged lymph nodes of both later cervical sides. She had a temperature of about 37.7 °C. Blood tests showed a moderate anemia, with hemoglobin values ranging around 9-10g/dl, a mild progressive decrease in lymphocytes (from 1060/microliters to 720/microliters), an increase in inflammatory markers (erythrosedimentation rate and C-reactive protein). Protein electrophoresis showed an increase of acute phase proteins (α1and α2-globulins) despite of a decrease in albumin and total protein values. Blood iron and transferrin were low, ferritin was 268.7 ng/ml (mildly elevated). There was a specific mild increase in the oncological marker Ca 125. Blood and urine cultures, procalcitonin, and quantiFERON®-TB Gold were negative (Table 1). The chest x-ray showed only an enlarged heart shape, which was consistent with an effect of her arterial hypertension. The electrocardiogram (ECG) was normal. Received: May 01, 2019 Published: May 20, 2019 ARTICLE INFO abstract

In suspicion of a lymphoproliferative disease, the patient performed an abdominal ultrasound, which showed an increased  vascularisation and increased diameter of the spleen; c.
Increased area of the spleen; d.
Contrast-enhanced CT of the pelvis: thickening of the left obturator muscle (white arrow) and mild effusion in the Douglas pouch (white arrowhead); d.
Contrast-enhanced CT: osteoaddensing lesion in the soma of the first thoracic vertebra D1 (white arrowhead).
The patient then performed a biopsy of left later cervical lymph nodes. The histological examination was consistent with a mixed cellularity subtype of classical Hodgkin lymphoma. The immunophenotyping was positive for CD30, CD15, PAX5, Fascine and negative for CD20 and CD3. In association with CT aspects, these clinical features were consistent with a stage IV disease, according to the 2014 Lugano classification (Cotswold's modifications applied to Ann Arbor classification) ( Table 2). During the hospital stay, the patient was treated with supportive and antibiotic therapy (since the initial suspicion of infectious disease). She was then referred to a Hematologic Center to start a specific diagnostic and therapeutic iter. is more frequent in Non-Hodgkin lymphoma (NHL) than in HL [2].
The extra nodal extension of the disease is essential to establish the type of treatment required [3]. The splenic involvement in HL and NHL has almost an overlapping prevalence and is often accompanied by liver involvement. Some Authors have observed that splenic involvement in Hodgkin's lymphoma is correlated with a younger age [4]. The splenic involvement is presumably via the hematogenous route [5]. Primary lymphomas of the spleen are very rare (less than 1%) and usually are represented by Non-Hodgkin lymphomas [6]. Splenic ultrasound, in cases of lymphoma involvement, is characterized by a sensitivity of 54% and a specificity close to 100% [7]. The increase in size of the organ is neither a necessary nor sufficient condition to confirm (or exclude) the presence of the disease. More frequently, splenomegaly occurs if the involvement is widespread [2,6].
At B-mode ultrasound examination, we can distinguish four main echo-texture patterns for splenic lymphomas: diffuse infiltration, "small-nodular" pattern, "large-nodular" pattern and "bulky" lesion [6][7][8]. Typically, Hodgkin lymphomas and low-grade Non-Hodgkin lymphomas show a diffuse infiltration or focal lesions with a size of less than 3 cm. Conversely, high-grade Non-Hodgkin lymphomas usually appear as lesions greater than 3 cm in size [6].
The ultrasound features of splenic lesions correlate with the severity of the pathology, being a diffuse pattern consistent with a low-intermediate grade and nodular lesions with an intermediate-high grade [8]. The lesions frequently appear hypoechoic or anechoic (so-called "cystic-like"), but they can rarely be isoechoic, hyperechoic or isoechoic with a hypoechoic halo (more rarely with a "target" appearance), and sometimes they can coexist. Hyperechogenic

Two-dimensional real-time shear wave elastography (SWE) is
an imaging technique that uses acoustic radiation force to stimulate the production of a linear vibration source and then uses special high-speed imaging to track the displacement of each point on the path of shear wave propagation [12]. Currently, the main application of shear-wave elastosonography (SWE) in the study of the spleen in hematological diseases is reserved for the study of the splenic response to primary myelofibrosis. There are still few studies on the use of SWE in splenic involvement in lymphoproliferative diseases [13,14]. About lymph nodes, the data from scientific literature are mainly related to later cervical and superficial ones. It is not possible to make a differential diagnosis of Hodgkin lymphoma and Non-Hodgkin lymphoma by ultrasound examination. They appear increased in size with a short axis equal to or greater than 10 mm.
They tend to be roundish, hypoechoic, with well-defined margins, and the hilum that loses its echogenicity. Many of these features are indistinguishable from those of metastatic lymph nodes. At the color doppler investigation, both the hilar and peripheral vessels are visualized, as opposed to metastatic lymph nodes, where the extensive necrosis and keratinization alter the hilar vascular tree6 [15].
The lymph node size and vascularization are good parameters for assessing the response to treatment. With regard to vascular indices, even if the literature is poor in this regard, it is generally agreed that there is an increase in RI (ranging from 0.64 to 0.84) compared to inflammatory or metastatic lymph nodes. It is generally believed that the RI of lymphomatous nodes is higher than those of reactive, tuberculous and normal nodes, and are lower than those of metastatic nodes [15]. US elastography appears to be a promising tool for diagnosing benign and malignant lymph nodes diseases, in selected populations [16].  [18].
A useful application is dynamic CEUS, a study of changes in quantitative parameters during ultrasound contrast agent administration (second generation, Sonovue®) The time-intensity curve (TIC) analysis has been applied to evaluate changes in wash-in phase, time to peak, intensity and wash-out phase of the ultrasound contrast agent, in patients receiving chemotherapy.
In general, diseased lymph nodes have a more rapid wash-in, and wash-out and a lower time to peak time [19]. Dynamic sonographic contrast enhancement in Hodgkins and non-Hodgkins lymphoma showed a delay in the time to peak enhancement after treatment.
Even the values of enhancement intensity and peak intensity appear to be lower after treatment. Dynamic contrast scanning using ultrasound is advantageous over similar techniques using CT or MRI in that it is radiation-free, has a high spatial resolution yet maintains a high frame rate, and can be performed repeatedly during the same examination. It appears to provide a new, timedependent dimension in the assessment of lymph node pathology and supplements the morphological information provided by grey scale and Doppler sonographic interrogation [15].

Conclusion
In modern medicine, ultrasound examinations definitely are handy tools to draw pathways of diagnostic workups. In our patient, given the clinical presentation, our first suspicion was about a lymphoproliferative disease. Ultrasound was useful to strengthen our hypothesis. Definitive diagnosis and staging were easily made with histology, immunophenotyping and contract-enhanced CT scan. That's why, in this specific case, we can affirm that "simpler solutions are more likely to be correct than complex ones", as the philosopher William of Ockham stated in the 14 th century.