Dela Salle Health Science Institute College of Medicine Dasmarinas, Cavite

General Data Patien H.D. a 39 years old male, catholic, Filipino, Residing at San Jose, Dasmarinas Cavite City Chief complaint: difficulty of Breathing History of present illness: Several months PTA, he experienced recurrent throat pains and dysphagia. He sought consult every now and then and was said to have tonsillitis. He was given several courses of unrecalled antibiotics which afforded temporary relief from time to time. He would have low grade fever along with the throat pains as well as occasional chills. Four months PTA he noticed a marbled sized nodule in his left upper neck area which was non tender but immovable. He again sought consult but this time, fine needle aspiration was done to the nodule which revealed chronic inflammation. He was again given unrecalled antibiotics which were unable to resolve the problem. He sorted then to herbal medicines as recommended by his neighbour and did not do any further consult. The neck nodule slowly increased in size during the next several weeks. He also noted on and off low to moderate grade fever. His dysphagia also worsened progressively that he is unable to swallow solids. One day PTA, he experienced difficulty of breathing which eventually prompted consult. Review of Systems (+) weight loss around 25% since 7 months (-) bowel, bladder habit changes (-) neurologic symptoms (-) dyspnea (-) occasional cough (+) generalized body weakness (+) easy fatigability (-) polyuria, polydipsia, polyphagia

Past Medical History: Treated for weak lungs during early adulthood. Treatment lasted for 6 months with unrecalled medications (-) hypertension, diabetes, asthma, allergies, (-) previous surgeries Family History: (+) hypertension, father. (-) diabetes, heart disease asthma, allergies Personal/Social History: Chronic alcoholic beverages drinker (1 bottle of gin daily since 18 years old) Smoker of 1 pack per day since 15 years old Frequents several night spots with promiscuous sexual practice Works as a radiology technician Physical Examination Awake, ambulatory, fairly nourished, in mid respiratory distress BP: 110/80 HR:95 bpm RR:26 cpm T:37.6 weight: 52 kg

(+) pallor. (-) jaundice Pale palpebral conjunctivae, anicteric sclera, (+) 6x5 cm upper cervical mass L, non movable. (+) enlarged left Tonsil around 3x4cm Symmetrical chest expansion. No crackles, no wheezing Normal cardiac rate and rhythm, no murmurs Abdomen globular, normoactive bowel sounds, no masses, no tenderness Fair pulse. No edema. (+) pallor on palms and soles Neurologic exam: oriented to time place and person. Nolateralizing signs. Normal reflexes

1. What Other information from the history would you want to elicit and Why? a. Family history. Anyone with a brother or a sister who has the disease faces an increased risk of developing Hodgkin's, though this may be due to similar environmental exposures rather than genetic factors. b. Past Epstein-Barr Or Human Immunodeficiency infection. People who have had illnesses caused by the Epstein-Barr virus, such as infectious mononucleosis, may be four times as likely to develop Hodgkin's disease as people who haven't had a past Epstein-Barr infection. c. Compromised immune system. Having a compromised immune system, such as from HIV/AIDS or from having an organ transplant requiring medications to suppress your immune response, also appears to put you at a greater risk of Hodgkin's lymphoma. d. Chemical exposure: Certain chemicals found in pesticide products such as lawn and garden chemicals, may increase the risk of developing lymphoma. Recent clinical studies suggest that the increased risk of pesticide exposure and NHLs may be confined to those with a history of asthma. 2. What other pertinent physical examination findings should you look for and why? a) Drenching night sweats Sweating is symptom of hodgkins disease and can often lead to nocturnal hydrosis commonly know as night sweats or bed sweats. This may be so extreme that the bed sheets and blankets become drenched. Night sweats are subjective reports of nocturnal sweating that results from an exaggeration of the normal circadian temperature rhythm. It is also the body's way of fighting infection, it may require the mobilization of immune cells and cytokines (such as interferon, Interleukin); and that these immune activities might account for causing night sweats, fever, and achy muscles. b) Itchy skin. Itching is one of the peculiar symptoms of hodgkin lymphoma. About 1025% of individuals suffering from hodgkin disease suffer from an intense itch. In some, the itching starts before the diagnosis of lymphoma is made. It is often felt as A burning sensation occurring on A particular area of skin, frequently on the lower legs. The cause of this itch is not definitely known. It is believed that some blood cells release chemicals near the nerves of the skin and irritates these nerves. We feel this as an itch. Itching in hodgkin has more importance than just being an uncommon symptom. It may be an indicator of A less favorable prognosis when associated with significant fever or weight loss. In some cases,

c) d)

e)

f)

g)

patients may actually break the skin with their fingernails in attempts to get some relief Consistency of the node A firm, rubbery node may indicate lymphoma (including hodgkin's). Pain following alcohol consumption: Classically, involved nodes are painful after alcohol consumption, though this phenomenon is very uncommon. Back pain Nonspecific back pain (pain that cannot be localized or its cause determined by examination or scanning techniques) has been reported in some cases of hodgkin's lymphoma. The lower back is most often affected Red-coloured patches on the skin, easy bleeding and petechiae Due to low platelet count (as A result of bone marrow infiltration, increased trapping in the spleen etc. I.E. Decreased production, increased removal) Trouble breathing or chest pain When hodgkin disease affects lymph nodes inside the chest or respiratory tract pathway, the swelling of these nodes may press on the windpipe. This can make you cough or even have trouble breathing, especially when lying down.

3. What will be the primary impression for this case? Give basis The primary impression on the patients case is Human Immunodeficiency Virus based on the physical examination manifesting recurrent throat pains, dysphagia, accompanied by occasional chills and an enlarged lymph node in the neck. Later symptoms include weight loss and occasional coughing. Also we consider his occupation as a radiology technician, smoking habits and promiscuous sexual activity as predisposing factors. Hodgkins Lymphoma is secondary because fever that does not does away, easy fatigability, generalized body weakness, weight loss and pallor were manifested. Orientation of the mass is on the unilateral left side of the neck (unilateral tonsillitis) which may be alcohol-induced. Age and gender was also taken into consideration due to its predominance to males ranging from 30-50 years age group. 4. In tabular form, enumerate your differential diagnoses and write down why they were ruled in or out.

NASOPHARYNGEAL CANCER

Rule In y The dysphagia and dyspnea of the patient may be caused by an obstruction particularly

Rule out Nasopharnygeal affectation Bloody discharge Epistaxis

by a nasopharyngeal tumor y This is caused by Epstein Barr Virus, an opportunistic infection having increased incidence among immunocompromised patients (like patients infected with HIV) Lump lymph nodes on

Nasal congestion Hearing loss Strigor Posterior cervical adenophaty Endemic in China

y SQUAMOUS CELL CARCINOMA IN THE NECK

Squamous cell carcinoma of the palatine tonsil typically presents as a unilateral mass in the oropharynx or as a mass in the ipsilateral neck indicating a lymph node involved with metastasis The tumor may cause obstruction in the neck which may lead to dyspnea and dysphagia As with all other cancer illnesses, there is observed weight loss, easy fatigability, and generalized body weakness It may affect the lungs that may lead to dyspnea It has consistent systemic signs and symptoms as with other carcinomas Immunocompromised patients like those having HIV infection are more susceptible to developing this

KAPOSI'S SARCOMA

There is absence of purplish colored nodules of the skin which are characteristic of Kaposis Sarcoma

LUNG CANCER

The patient is a chronic alcoholic beverage drinker for 21 years There is also increased risk of developing lung cancer among patients infected with HIV

There is symmetrical lung expansion No crackles No wheezing Normal cardiac rate and rhythm, no murmurs meaning heart function is not impaired by any lung obstruction

HEPATOCELLULAR CARCINOMA

TUBERCULOSIS

The patient is a smoker of 1 There is also increased risk pack per day for 24 years of developing hepatoma among patients infected with HIV No masses or tenderness in the abdomen This may explain dyspnea, There is no chest pain, weight loss, pallor, and coughing out of blood, and easy fatigueability prolonged productive coughing which are Tuberculosis may arise established signs and from an opportunistic symptoms of tuberculosis infection by Mycobacterium tuberculosis HIV infection is one of the most important factors that may make a patient more susceptible to TB infection Chronic smoking of the patient makes him more susceptible to developing tuberculosis

INFECTIOUS MONONUCLEOSIS

This presents as fatigue, There is no observed weight loss, body weakness petichiae, splenomegaly, and lymphadenopathy and hepatomegaly leading to dyspnea and dysphagia This is caused by Epstein Barr Virus infection which is closely associated with immunocompromised patients

5. What other laboratory exams would you want to request to help you in the diagnosis and treatment of this patient? Imaging studies should first be conducted. Ultrasonography can be requested to help differentiate a solid mass from a cystic mass or congenital branchial cysts and thyroglossal cysts from solid lymph nodes, neurogenic tumors, and ectopic thyroid tissue. Ultrasound can help differentiate soft tissue swelling from a fluid or pus-filled mass. However, a CT Scan is definitive. It can enhance further differentiation of solid masses from cystic masses, determine the location of the mass whether it is within a glandular structure or it is a free nodal lesion. Both tests can help differentiate soft tissue swelling from a fluid or pusfilled mass. If results of the imaging tests show that there is a presence of abscess, aspiration of the abscess should be conducted followed by gram staining or culturing of the organism. If there are no abscesses, then skin tests for tuberculosis can be conducted. If negative, CBC, differential and platelet count should be obtained. If there is leukocytosis, usually with a neutrophil predominance along with lymphopenia, a one week antibiotic trial should be conducted. If the mass decrease in size, continued observation should be conducted. if there is no response to treatment, open biopsy and flow cytometry of the tumor should be conducted to determine the presence of malignant cells and if there are any invasion. If there is malignancy, tumor markers should be identified to know the type of neoplasm. Positive for cytokeratin indicates an epithelial tumor. While a vimentin positive test indicates mesenchymal origin and positive for leukocyte common antigen concludes the presence of a hematologic malignancy such as lymphoma. Fluorescent In situ Hybridization can also be conducted to determine the presence of translocations that are specific for lymphomas. Positive CD 15 and CD 20 immunotyping concludes the presence of Hodgkins Lymphoma. Human immunodeficiency virus (HIV) serology should also be conducted to determine to confirm if the viral infection is a factor in the development of a neck mass. 6. based on your primary diagnosis, how would you explain the patients symptoms and manifestations? Dysphagia and difficulty of breathing due to the impingement of the trachea and the esophagus caused by the large cervical mass providing obstruction of the airway and food passage.

Weight loss and generalized body weakness due to malignancy wherein there is an increased metabolic state of the cancer cells which consumes the energy reserves of the body Fever and weight loss are B symptoms or the systemic symptoms of Hodgkins Lymphoma. studies showed that fever in patients with Hodgkinss Lymphoma is due to the spontaneous endogenous production of pyrogens by blood, spleen and lymph nodes. The mechanism for the "spontaneous" and continuing production of pyrogen by these tissues is not clear. By analogy with results of studies of blood and exudates leucocytes, an activator, such as a microbial product or antigen, presumably initiates the process of pyrogen synthesis and release from tissue PMN or mononuclear cells. Unilateral Tonsilitis - Unilateral tonsillar enlargement may be a benign hyperplastic reaction to a localized Hodgkins lymphoma in the ipsilateral cervical lymph nodes. The exact mechanism of the benign reactive hyperplasia in response to regional tumor is still unknown. The most widely accepted theory is that of an immunological response to the tumor antigens. This unilateral tonsilar enlargement in response to a local lymphoma is rare because unlike lymph nodes, the lymphoid tissue of Waldeyer's ring has no afferent lymphatic channels. In this case, the most likely mechanism of the reactive tonsillar changes is the obstruction of lymphatics in the tonsillar lymph nodes by the Hodgkins Lymphoma or the cervical neck mass causing retrograde flow of lymph to the tonsil. Pallor evidence of an increased rate of erythropoiesis in all of the patients with Hodgkins disease. This was manifested by normoblastic hyperplasia of the marrow, a moderate reticulocytosis and increased plasma iron clearance rates. The shortened red cell survival times were associated with the increased plasma iron clearance rates. The anemia is due to the inability of increasing the rate of red cell production sufficiently to compensate for the increased rate of destruction. 7. Draw the schematic diagram of the pathophysiology of your primary impression

HIV Infection

Virus becomes established in lymph nodes

Selected tropism for Thelper cells

Marked Follicular Hyperplasia

Depleted T-helper cell

Hodgkin s Lymphoma: RS cell neoplasm

Enlarged Cervical Lymph Node

Compromised immune system

Suppressed TH1 Response

R-S cell release factors

GM- CSF

Opportunistic infections (Oral)

Compression of other respiratory structures / obstruction of airway

Enlarged Tonsils

Increased MonocyteMacrophage Infiltration/ activation/ accumulation

Chronic Inflammation

Tonsilitis

Unbalanced/uncontrolled proliferation of cytokines

Dysphagia

Anorexia Altered cytokines in hematopoietic process Weight Loss

Breathlessness/ difficulty of breathing

Anemia

Fever

Easy Fatigability

8. What treatment modalities can you offer to the patient? Give all that may apply (pharmacologic and non-pharmacologic) HIV infection is currently incurable. However, there are a lot of palliative treatment modalities available which could potentially delay its progression to AIDS. Highly Active Antiretroviral Therapy (HAART) is a broad treatment strategy which is, as the name implies, composed of multiple antiretroviral drugs that could slow the spread of HIV in the body. A combination of three or four drugs are used, each of which are intended to block a specific phase in the life cycle of the infective retrovirus. HAART has been, in majority of the cases, very helpful in preventing incidences of opportunistic infections. It also allows more aggressive chemotherapy and less antagonistic manifestations of lymphoma as compared to those HIV positive individuals who were not given such treatment. With this development, the management of Hodgkins Lymphoma secondary to an HIV infection became less problematic. Aside from the typical symptoms of malignancy, HIV-HL manifests systemic B symptoms such as fever, weakened immune state, and/or loss of greater than 10% of the normal body weight. Like all other complex illnesses, treating such will require an array of approachesthe standards being chemotherapy, surgery, and/or radiation therapy. Chemotherapy is the most commonly used treatment modality. It is designed to attack the rapidly dividing cells that form the cancerous lesions. In lymphomas, combination chemotherapy of a number of different drugs is typically utilized. However, the exact number and types of drug used largely depends on the patient and the stage of the disease in question. The course of therapy may vary; nevertheless, the standard regimen is ABVDAdriamycin (Doxorubicin), Bleomyycin, Vinblastine, and Decarbazine. If the illness is resistant, many other treatment forms like MOPP (Mustargen, Oncovin, Procarbazine, Predniosone), COPP/ABVD(cyclophosphamide, vincristine. procarbazine, prednisone, doxorubicin, blemycin, vintiastine, and dacarbazine), ChIVPP (Chlorambucil, Vinblastine, Procarbazine, Prednisone), and Stanford V may be used. Non chemotherapy options are also currently available: bone marrow transplantation, radiation therapies, immunotherapy, and clinical trials, to name a few. Bone marrow transplantation, coupled with Peripheral blood stem cell transplantation allows the use of high doses of chemotherapy drugs before a subsequent immune system rescue. The use of radiation therapy, on the other hand, has remarkably decreased since the dawn of new chemotherapy drugs. Nowadays, they are more useful to patients with a much localized disease, or to those who are quite unresponsive to the conventional drugs. Immunotherapy also shows promise in terms of treatment. One of the most notable immunotherapeutic drugs is Rituximab, a monoclonal antibody against the protein CD20 found on B-cell surfaces. However, since the type of Hodgkins Lymphoma that is more likely affecting the patient is a Lymphocyte Depleted Type, Rituximab would most probably

not elicit any beneficial effects. This is because the CD20 protein is absent in that particular type of HL. Clinical trials may also be beneficial to patients with HIV-HL, especially to those who poorly respond to the conventional treatment modalities. To evaluate and re-evaluate the treatment responses in most of the treatment plans, a PET scan could be very helpful since a negative scan can be almost always associated to a more favorable prognosis. Another possible strategy, though less popular, is the so-called watchand-wait. This modemainly for indolent cases of HLis characterized by the absence of any direct treatment. Instead, the patient will only be monitored carefully by the physician while waiting for any observable disease states to surface. Because the problem of HIV infection is yet to be resolved, health care providers may have to make do on preventing the transfer of disease to other individuals, as well as other complimentary forms of management. An ongoing anti-retroviral treatment of HIV may decrease the chances of its transmission to another person; however, it is not an absolute guarantee of non-transmission. Complimentary therapies, on the other hand, could work in adjunct to the conventional treatment modalities. Some examples are biologically based practices such as taking probiotic/prebiotic substances, and vitamins/minerals supplements. Relaxation techniques, yoga, aromatherapy, and the likes may also be beneficial to a certain extent. HIV patients also tend to use more energy in doing tasks, causing greater loss of weight. Therefore, an increase in the amount of calories taken in is advisable. The loss of appetite may be circumvented by encouraging the patient to eat several small meals a day. Exercise and appetite stimulants may also increase the desire for food. HIV Infection, as well as lymphomas may also necessitate professional counseling and spiritual guidance.