Unusual Presentation of Laryngeal Carcinoma

Naushaba I Khalid, MD, Associate; Naga V A Kommuri MD, Associate; Munasinghe Rajika MD

Department of Internal Medicine, Sinai-Grace Hospital/Detroit Medical Center

Introduction:

Squamous cell carcinoma of the neck presents with a constellation of symptoms that depend on the tumor site. These manifestations range from local tenderness to respiratory compromise. Laryngeal abscess is a very rare presentation of squamous cell carcinoma of the larynx

Case Report:

A 37 yr old AAM presented with a history of hoarseness, dysphagia and left sided neck swelling. On examination he had diffuse, tender, warm swelling in the anterior part of the neck with predominant left side involvement. Initial investigations revealed that the thyroid functions tests were normal, and he was treated as subacute thyroiditis but the swelling increased. A soft tissue radiograph of the neck showed deviation of trachea to the right and the presence of a soft tissue cystic mass in the neck anterior to and involving the thyroid cartilage, predominantly below the level of the hyoid. CT of the neck showed a mixed cystic and solid mass involving the isthmus and left thyroid gland, continuous with the laryngeal mass also involving the left vocal cord and supraglottic region. The patient underwent pan endoscopy that demonstrated a large exophytic, infiltrative lesion in the supraglottic larynx, primarily on the left side, extending over the anterior commissure to the right, blocking the true cords. Biopsy of the vocal cords revealed supraglottic squamous cell carcinoma and the anterior neck mass biopsy showed acute inflammatory infiltrate [abscess] without any evidence of malignancy. Staging showed that it to be T3 N2A M0. Incision and drainage of the abscess was performed followed by treatment with chemotherapy and radiotherapy.

Discussion:

This case highlights the need to be aware of unusual lesions that may arise in the region of the thyroid gland. The presentation of this lesion as a thyroid mass is unusual and serves to remind clinicians that the differential diagnosis of a thyroid mass should include the diagnosis of an abscess due to direct extension of a primary neoplasm of the upper aero digestive tract.

BIOCHEMICAL ANALYSIS OF AMYLOID PROTEIN OF PERCUTANEOUS RENAL BIOPSIES

Ziad Zaky M.D. (Associate), Juris J. Liepnieks PhD, Merrill D. Benson M.D.

Department of Internal Medicine Sinai-Grace hospital/Wayne State University, Detroit, Michigan. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.

Introduction

Amyloidosis is characterized by the pathologic deposition of at least 20 different precursor proteins. Despite the differing chemical nature of these molecules, all forms of amyloid have identical tinctorial and ultrastructural features and, as a result, cannot be differentiated microscopically.

Objective

To determine if sufficient tissue amyloid can be obtained by percutaneous renal biopsy to differentiate the type of amyloid protein, AL, AA, or hereditary. If successful, it would be recommended to do biochemical analysis for all renal biopsies with diagnosis of amyloid.

Methods

Amyloid protein was isolated from sixteen percutaneous renal biopsies using microextraction techniques. Samples were analyzed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Separated proteins were electrophoretically transferred to Polyvinylidine Difluoride (PVDF) membrane for sequence analysis. A portion of isolated protein was digested with trypsin and fractionated by reverse phase high pressure liquid chromatography (HPLC). Samples were analyzed by Edman degradation technique.

Results

Analysis of the pool on SDS PAGE of six patients showed bands at 14 and 20 KDa. One patient showed bands 14, 18, 20, 25, 30 and 40 KDa. The type of amyloid protein was as follows: λVI light chain was identified in three patients, қ light chain in two patients and AA was identified in one patient. The results are still pending.

Discussion/Conclusion

The type of amyloid often can be inferred from immunohistochemical analyses or immunologic assays, but, the results may be inconclusive owing to the lack of appropriate antisera. Thus, to establish unequivocally the nature of the amyloid protein, it is essential that the material be extracted from the specimen and analyzed chemically. The ability to diagnose precisely the type of amyloid protein has become increasingly important given the development of specific therapies. These include high-dose chemotherapy and organ transplantation for AL and transthyretin (ATTR), respectively, as well as the use of inhibitors of fibril formation, amyloidolytic drugs. Recently, active or passive immunotherapy has been used to prevent pathologic fibrillar deposits. Thus, to provide optimal patient care, we recommend that pathologists not only establish a diagnosis of amyloidosis but also to ascertain the type of protein that is deposited as amyloid.

Recurrent Pneumothorax associated with Invasive Pumonary Aspergillosis in HIV patient

Ruchika Jain, MD (Associate) Wasif Hafeez (Member) Department of Medicine, Sinai Grace Hospital Detroit, Michigan.

Introduction : Invasive Aspergillosis is a significant cause of morbidity and mortality in severely immuno-compromised hosts. Isolated cases of invasive pulmonary aspergillosis have been reported in patients with AIDS. Although it is not an AIDS-defining infection any more,It is an important and commonly fatal complication of advanced HIV disease. We report a case of invasive aspergillosis presenting as recurrent pneumothorax in an AIDS patient with history of COPD.

Case Report: A forty-eight year old male with history of hypertension, COPD, HIV and recent pneumonia presented to the emergency department with progressive dyspnea, and left sided pleuritic chest pain . Chest x-ray revealed left tension pneumothorax which was treated with chest tube insertion. However due to persistent chest tube air leak and worsening pneumothorax, he underwent left thoracotomy and stapling of apical bullae and wedge resection of the lingular segment. GMS staining for fungus revealed a focus of fungal hyphae present in an area of intense inflammation and morphologically resembling aspergillus species. He was started on Voriconazole and discharged to home. One week later he presented again to the hospital with similar complaints. Chest X-ray revealed recurrent left-sided tension pneumothorax. He again underwent chest tube insertion and subsequent left pneumonectomy. GMS stains performed on multiple sections showed no evidence of fungal organisms or PCJ infection.

Discussion: Spontaneous pneumothorax in HIV patients is usually associated with Pneumocystis jeroveci pneumonia , pulmonary tuberculosis or bacterial pneumonia. Invasive aspergillosis also remains an enigmatic disease that occurs predominantly among immuno-suppressed patients including those with HIV infection and can rarely present with pneumothorax, pneumo-mediastinum and pneumo-pericardium. Concurrent predisposing factors for Aspergillus infection among HIV patients include granulocytopenia, PCJ, CMV, bacterial and /or other fungal pneumonia, underlying chronic lung conditions, use of broad spectrum antibiotics , chemotherapy and steroids . .Diagnosis of invasive pulmonary aspergillosis is usually done by BAL cytology and or culture, Tracheal, trans -bronchial or open lung biopsy, sputum examination, thoracentesis or serum antigen detection .Early diagnosis and aggressive antifungal treatment is recommended Surgical intervention can be tried in certain patients However mortality rate remains high despite recent advances in therapy.

Purpura Fulminans in Septicemia-An Association with underlying Protein C &S Defeciency.

Ruchika Jain (Associate), Rashad Syed Khazi (Associate), Wasif Hafeez (Member) Department of Internal Medicine, Sinai Grace Hospital Detroit Michigan.

Introduction : Presenting with skin discoloration, fever, and septic shock, purpura fulminans is a rare syndrome of hemorrhagic infarction of the skin, extremity loss, and intravascular thrombosis that can progress rapidly to disseminated intravascular coagulation, vascular collapse and death . The majority of the patients are children, but adults can be affected . The most common infectious agents associated with purpura fulminans are Neisseria meningitides, Hemophilus influenzae, Streptococcus pneumoniae and Varicella zoster . We present a case of Purpura fulminans in association with severe sepsis due to poly microbial infection with Enteroccus faecalis and E coli .

Case report: An eighty-three year old female with history of Squamous cell carcinoma of right lower extremity, Oglivie syndrome, and CVA was admitted with change in mental status ,fever ,hypotension, and tachycardia. Blood cultures were positive for Vancomycin resistant Enterococcus faecalis and ESBL producing Escherichia coli. Pt was started on Meropenam and Linezolid . On fifth day of admission patient developed extensive irregular areas of skin necrosis with rim of surrounding erythema with mild tenderness. Protein C activity was found to be 41% and protein S activity was 58%.D-dimer levels were 24.40 and fibrin monomers were also present Pt was diagnosed to have Purpura fulminans with underlying protein C&S deficiency.

Discussion: Purpura fulminans is an uncommon disorder first described by Guelliot in 1884.It can be identified in three clinical conditions.1)In patients with pre existent abnormality of protein C or protein S anticoagulant pathway; 2)In patients with acute severe bacterial infections called acute infectious purpura fulminans; and 3) in patients without known abnormalities of protein C pathway or acute infections ,termed idiopathic purpura fulminans. Sepsis induced purpura fulminans is associated with high mortality due to multiple organ dysfunction. Necrotic lesions usually progress to distal ischemia, and skin grafting and limb amputation are often required .Early antibiotic administration and intensive care management are crucial to patients survival. Adjuvant therapies against inflammatory and coagulation cascades and promoting fibrinolysis are still controversial .Since Purpura fulminans is a syndrome, not a specific disease; therefore treatment should be aimed towards underlying infection with ongoing supportive management.

Mitogen-activated protein kinase (MAPK) inhibition via MAP kinase, epidermal growth factor receptor, or erbB-2 leads to return of estrogen-dependence and anti-estrogen response in ERα- breast cancer

Prakash Vishnu, Jill Bayliss, Amy Hilger, Kathy Diehl, and Dorraya El-Ashry

Dept. of Medicine, Sinai-Grace Hospital, Wayne State University, Detroit, MI

Background/hypothesis: Breast cancer presents as estrogen receptor alpha (ERa) positive or negative. ERa-tumors have a poor prognosis and are resistant to anti-hormonal therapy. ERa- tumors frequently show overexpression, amplification, and/or hyperactivation of growth factor signaling, especially of the erb-B family, resulting in hyperactivation of MAPK pathway. Previously, we have shown that hyperactive MAPK causes reversible down regulation of ERa. In this study, we sought to determine if the inhibition of MAPK activity in ERa- breast cancer cell lines and tumor specimens could restore ERa expression and anti-estrogen response.

Methods: Three established ERa- cell lines, SUM229 (ERα-/PR-/H2N-/EGFR+), SUM190 (ERa-/PR-/H2N+/EGFR+), SUM149 (ERa-/PR-/H2N-/EGFR+), and three tumor cell cultures derived from dissociation of ERa- breast tumors, DT5 (ERa-/PR-/H2N-), DT13 (ERα-/PR-/H2N+) and DT16 (ERα-/PR-/Her2/neu-) were used in this in-vitro study. Inhibition of MAPK was achieved by MEK1/MEK2 inhibitor, U0126 (10mM). Western blotting was performed to visualize the re-expression of ERa. A colorimetric growth assay for cell proliferation and viability was performed using WST-1 to assess anti-estrogen sensitivity in these cells by treating them with 4-hydroxy-tamoxifen (selective ER modulator) and fulvestrant (ER antagonist) in combination with U0126.

Results: Inhibition of MAPK resulted in re-expression of ERa protein in all three established ERa- cell lines and all 3 ERa- tumor cell cultures. While having no growth inhibitory effects on its own, U0126 restored the growth inhibitory effects of both 4-hydroxy-tamoxifen and fulvestrant.

Conclusions: These results support our hypothesis that there exists a population of ERα- tumors where up-regulated growth factor signaling is directly involved in the generation of ERα- phenotype by repressing ERα expression; and further, this reversible down-regulation may be targeted clinically such that this repression can be reversed by inhibiting MAPK, resulting in re-expression of ERα and restoration of tamoxifen sensitivity.

RENAL TUBULAR ACIDOSIS TYPE-1 AND NEPHROLITHIASIS IN A PATIENT WITH SARCOIDOSIS

Rao Ali Hashim Khan, MD, Associate; Rama Nadella, MD, Associate; Irfan Omar, MD, Member, Department of Medicine, Sinai Grace Hospital, Detroit Medical Center, Detroit, MI.

Introduction:

Sarcoidosis is a chronic, multisystem disorder of unknown cause. All parts of the body can be involved, but the organ most frequently affected is the lung. Involvement of the skin, eye, liver, and lymph nodes is also common. Nephrolithiasis occurs in approximately 1 to 14 % of patients with sarcoidosis, but association of renal tubular acidosis (RTA) with sarcoidosis is unusual.

Case Report:

This is a 45 years old african american female with past medical history of sarcoidosis diagnosed 17 years ago. Over the course it was complicated by blindness, ventilator dependant respiratory failure and nephrolithiasis. This time patient presented with shortness of breath of two days duration, left flank pain radiating to groin and was found to have left renal calculi and diagnosis of renal tubular acidosis (RTA) type-1 was made based on following laboratory values: serum bicarbonate of 15 mMol/L, serum chloride 115 mMol/L, serum calcium 9.5 mMol/L, serum anion gap of 16, urine pH of 5.5 to 6.0, urine anion gap of +44, urine calcium of 20.3 mg/dl. Patient’s vital signs and physical examination were unremarkable. Chest X-ray was negative. Both ultrasound and CT-scan of kidneys were negative for nephrocalcinosis.

Discussion:

Sarcoidosis is known to be associated with both nephrolithiasis and nephrocalcinosis but only nephrocalcinosis is a known etiology of RTA. Hence, in our patient we suspect association of sarcoidosis with RTA type-1, in the absence of nephrocalcinosis. Nephrolithiasis in this case could be secondary to both sarcoidosis and distal RTA. This case suggests that it is important to identify and treat distal RTA to prevent recurrence of renal calculi in patients with sarcoidosis. This patient was treated with sodium bicarbonate and her acidosis improved with serum bicarbonate reaching above 20 mMol/L. We expect that treatment of RTA type 1 will certainly slow if not halt the progression of nephrolithiasis in this patient with active sarcoidosis.

Response to imatinib mesylate in a patient with idiopathic hypereosinophilic syndrome

Ramchandani Harsha MD, Associate; Solh Melhem MD, Associate; Robin Adam Medical student,

Department of medicine, Sinai Grace Hospital, Wayne State University, Detroit, MI.

INTRODUCTION

Hyper Eosinophilic syndrome (HES) is a heterogeneous group of rare disorders characterized by sustained and otherwise unexplained overproduction of eosinophils with organ involvement and consecutive dysfunction.

Differential diagnosis between the HES and the related chronic eosinophilic leukemia (CEL) relied on the identification of signs of clonality that allowed, when present, the reclassification of patients as CEL. Treatment for CEL and a subset of HES, positive for the FIP1L1/PDGFRA mutation remains the same, however the prognosis varies. When either one is complicated by eosinophilic lung deposits at presentation, it becomes more challenging to differentiate the diagnosis from chronic eosinophilic pneumonia which has a different treatment.

CASE REPORT

A 50 yr old African American female with multiple admissions to the hospital for shortness of breath, cough and urticaria in the last 7 years was readmitted for the same symptoms. Cough was nonproductive, not associated with fever or chills. No weight loss or night sweats reported by the patient who has a non-significant past medical and past surgical history. Blood labs showed absolute eosinophil count of 21.0 K/ cumm which was not in response to any allergen as a complete allergy workup failed to identify any precipitating factor. She had an elevated alkaline phosphatase, tryptase and IL-6 consistent with a myeloproliferative process. Chest X Ray showed interstitial markings which may relate to interstitial pneumonitis and focal consolidation in the posterior right lower lobe likely representing pneumonia. Bronchoscopy showed bilateral nodular infiltrates with eosinophilia. Flow cytometry and FISH provided CD3-/CD4+ predominance cells. Molecular testing was positive for the FIP1L1/PDGFRA mutation.Based on the above work up, patient was diagnosed as Hypereosinophilic syndrome with myeloproliferative features and was started on imatinib. Patient responded to the treatment with Imatinab at dose of 100mg/ day. Eosinophil count dropped to 10.2k/cumm.The cough and other disease features were subsequently suppressed by the tyrosine kinase inhibitor, imatinib.

DISCUSSION

Idiopathic hypereosinophilic syndrome remains a serious condition with a poor prognosis for most patients, unless treated. Multiple case series have demonstrated efficacy of Imatinab in treating patients with FIP1L1/PDFGRA-associated HES with clinical, hematological, and molecular remission documented in the majority of patients. Response rates are very high, with rapid resolution of clinical symptoms and normalization of eosinophil counts generally occurring within one to two weeks. Because of the marked sensitivity of this condition to imatinib therapy, identifying these patients is also now of considerable clinical importance as this group of patients are not responsive to steroids, the treatment of choice in HES without myeloproliferative features

Antimalarial Drugs Induce Apoptosis and Differentiation in Breast Cancer and Inhibit Growth of Stem Cells

Melhem Solh , M.D., Catherine Lobocki, M.S., Carly Collins, B.S, Linda Dubay M.D. FACS, Stephen Remine, M.D., FACS.

Wayne State University/Detroit Medical center- Sinai Grace Hospital

Department of Surgery, Providence Hospital- St John Health System

Objectives: Antimalarial drugs have been brought into the field of cancer therapy in the last few years. It is believed that quinidine induces apoptosis in cancer cell lines and induces differentiation in multidrug resistant breast cancer. The purpose of this study was to examine the growth inhibitory and cellular differentiation effects of the antimalarial drug quinine on four breast cancer cell lines (MCF7, T-47D, SKBR3 and BT474) as well as on a nude mice model.

Methods:

InVitro: Estrogen receptor(ER) positive (MCf-7, T47D), ER negative SKBR3 and weakly ER positive BT474 were seeded in 96 well plates then exposed to quinine. Growth inhibition was determined using the colorimetric MTT assay after 4 and 7 days of drug treatment. Lipid visualization using the Oil Red O stain was used to assess cellular differentiation.

In vivo: 20 mice were divided into 2 groups; breast cancer cell lines were implanted in the axillae of mice till a tumor volume of 200mm3. Mice were treated with intraperitoneal injections for 6 weeks then tumors were harvested for apoptosis, differentiation, ER positivity and growth.

Results: Both time and dose dependent effects were demonstrated. The IC50’s for MCF7, T-47D and SKBR3 was 14 – 29M quinine, respectivel. The BT474 cell line was relatively resistant to all drugs tested. Quinine showed a significant decrease in growth (p < 0.02), as well as a dramatic increase in lipid staining after 4 or 7 days of treatment compared to control. Quinine was also further tested as a growth inhibitor of breast cancer stem cells in triple negative cell lines as a potential adjuvant to prevent tumor dormancy and recurrence.

Conclusion: Quinine can cause cell death and induce differentiation in breast cancer and a significant growth inhibitory response. Quinie has proven to inhibit stem cell growth to the same extent as as tumor cells and hence, it prevents tumor stem cell dormancy-a potential reason of malignancy relapse. The potential of using antimalarial drugs in patients with advanced cancer and are not amenable for conventional chemotherapy should be further studied in phase 2 trials as the safety profile of the drug is already available.

PSEUDOMONAS LUTEOLA BACTERAEMIA IN A PREVIOUSLY HEALTHY WOMEN.

Kamal Abu-Rashed, M.D, Syed Raza, M.D, Marc Feldman, M.D, FACP, Associate Program Director, Department of Medicine, Sinai Grace Hospital

Wayne State University, Detroit MI

Pseudomonas luteola is a rare clinical infection, in which no epidemiological trend has been established.

It has been reported in several unrelated diseases such as colon cancer, peritonitis and catheter-related infections. We present a case of a previously healthy female with pneumonia and P. luteola bacteraemia.

We report a 26-year old female presenting with a 3-week history of shortness of breath and a increasing need to use her metered- dose inhalers for symptoms of asthma. Physical exam revealed a temp of 101.3, use of her accessory muscles to breath, wheezing and a pulse ox < 90% and at that time the patient was intubated. A serum leukocyte level was 31,700 ( 93% neutrophils, 1.6% lymphocytes, 2.5% monocytes). Blood cultures were drawn CXR revealed a pathy pulmonary infiltrate in the right middle lung. Intravenous ceftriaxone and doxycycline were begun. The next day blood cultures came back positive for gram-negative bacilli, cefepime and tobramycin was then begun for good gram-negative coverage. The patient subsequently progressed to an ARDS-like picture with worsening infiltrates bilaterally. The organism that later grew on MacConkey agar, was identified as Pseudomonas Luteola , sensitive to both cefepime and tobramycin. White blood cell count remained elevated for the next 9 days at 34,000. Doxycycline was then intiated and the leucocytosis began to trend downwards after 48hrs. The patient was extubated after clinical improvement and follow up blood cultures were negative. A screening colonoscopy, which was normal, was performed because P. luteola had been previously shown to be associated with colon cancer. Endocarditis has also been associated with P. Luteola, although a transesophageal echocardiogram did not reveal any valvular vegetations on this patient.

Previously, P. luteola was noted in patients with bacteremia, endocarditis, meningitis, peritonitis, and osteomyelitis. The diversity of the 17 published case reports does not reveal an epidemiological trend.

This case suggests that the spectrum of disease caused by this bacteria may continue to expand.

CLINICAL IMPLICATIONS OF INCIDENTAL LEFT BUNDLE BRANCH BLOCK(LBBB)

Naga VA KOMMURI MD,ASSOCIATE; Rajika Munasunghe MD, Department of Internal Medicine, Sinaigrace HOSPITAL/Detroit Medical Center, Detroit, MI.

Introduction:

Electrocardiogram has been one of the most common diagnostic tests in routine clinical practice. As a result incidental LBBB in asymptomatic patients is becoming more frequent, raising clinical questions and concerns about the significance of this finding.

Clinical Question:

What is the risk of cardiovascular related problems in asymptomatic patient with incidental LBBB on routine electrocardiogram?

Methods:

Data Source: Literature search was performed using the following search engines: Ovid, Pubmed, and Cochrane. Only case control and cohort studies were included since there are no randomized controlled studies to date. Key search words were LBBB, asymptomatic, incidence, prevalence, complications, clinical approach.

Results:

We found fifteen studies relevant to the clinical question. Based upon these studies the incidence of LBBB is between 0.16%-1%. Incidence increases with age [Imanshi et al]. Incidental LBBB is a marker of slowly progressive degenerative disease of heart [Errikson etal]. There is increased risk of developing cardiovascular disease [21 % in isolated LBBB vs. 11% in controls, p=0.04] and mortality [p=0.001] related to cardiac causes in this group of people [Fahy et al]. LBBB leads to abnormal ventricular activation causing asynchrony and global cardiac abnormalities [Grines etal]. People with incidental LBBB have a compromised long term follow up comparable with conventional cardiac risk factors [Miller etal]. In this subset of population there is increased risk of AV block and coronary death.

The clinical consensus in the management of incidental LBBB is further evaluation using Holter ECG and echocardiogram. Based upon these results patients can either be followed up or further evaluated using EP study and Myocardial Perfusion imaging. Interventional options based upon these results being Coronary angiography, Permanent pacing [Francia etal]

Conclusion:

Incidental LBBB is not a benign finding. Presence of isolated LBBB denotes a high risk patient for cardiovascular complications. Asymptomatic LBBB is underestimated and patients have a compromised follow up if compared with patients who have conventional cardiovascular risk factors. LBBB is associated with increased mortality due to cardiac causes.

A rare case of Eustachian valve endocarditis: An unusual presentation of right sided endocarditis

NAGA VA KOMMURI, MD, Associate, MALINI VENKATRAM, MD, Associate, RAJIKA MUNASINGHE, MD, Department of Internal Medicine, Sinaigrace HOSPITAL/Detroit Medical Center, Detroit, MI

Introduction:

Endocarditis of the right side of the heart is commonly associated with intravenous drug use, congenital heart disease or indwelling central venous lines. Eustachian valve [EV] is an endocardial fold localized between the inferior vena cava and the right atrium to direct the blood flow in the fetal circulation from the vena cava through the foramen ovale into the left atrium. Eustachian valve endocarditis is extremely rare and only 17 cases are reported in literature so far. There are no prior reports of EV endocarditis following AICD placement.

Case report:

A 42 year old African American Male presented two months after Coronary artery bypass surgery and AICD placement with lethargy, fever, abdominal pain and diarrhea. On examination, he had a fluctuant swelling without signs of inflammation around the AICD site suggestive of seroma. Initial work up revealed leucocytosis with neutrophilia and the serial blood cultures showed methicillin sensitive staphylococcus aureus (MSSA). Endocarditis was suspected and a trans- esophageal echocardiogram was obtained which showed vegetation on the Eustachian valve. Bacteremia persisted despite suitable antibiotic treatment. The source was suspected to be AICD which was removed and subsequent culture from the tip of AICD leads showed MSSA with similar sensitivities confirming the source for endocarditis. After treating with antibiotics he improved clinically and the blood cultures became negative.

Discussion:

The EV is an embryological remnant of the sinus venosus. EV endocarditis is characterized by clinical signs and symptoms of right-sided infective endocarditis in association with infective vegetations. The duration and the choice of antibiotics are similar to tricuspid endocarditis. The role of antibiotic prophylaxis and surgery in EV endocarditis is unknown.

Conclusion:

Endocarditis of the EV is a rare and probably under diagnosed entity. With the increase in the use AICD devices, clinicians should be aware of the possibility of EV endocarditis following AICD lead infection and consider TEE early to evaluate for this complication.

SQUAMOUS CELL CERVICAL CANCER IN A PATIENT WITH T CELL IMMUNE DEFICIENCY

Raihan Rabbani MD, Associate, Rashad Khazi Syed MD, Associate, Abhinav Agarwal MD, Associate, Abu Fazal Sheik Mohammed MD, Associate. Department of Medicine, Sinai Grace Hospital, Detroit Medical Center, Detroit, MI.

Introduction:

Most cases of squamous cell cervical cancer are associated with persistent HPV infection and are attributed to the failure of the immune system to eliminate the HPV from the body. In most of the cases, natural immunity clears HPV before the development of dysplastic lesions. Thus, any immune deficiency to HPV (as a part of general or specific) is associated with an increased risk of developing Cervical Cancer.

Case:

A 38year old female patient with history of dysphagia was being evaluated for anemia presumably due to blood loss from irregular vaginal bleeding. She also gave a history of postcoital bleeding and high risk sexual behavior. Her dysphagia was diagnosed as Candidal Esophagitis and treated with fluconazole 3 months ago. She was also treated for a pelvic abscess by percutaneous drainage and antibiotics. An endocervical biopsy demonstrated poorly differentiated squamous cell carcinoma. Testing for HIV 1 & 2 infection by ELISA was negative on two occasions. Further workup for immune deficiency revealed CD8 Lymphopenia (252, 18%) with an increase in CD4 Lymphocytes. The patient was discharged with the instruction to follow with gynecological oncologist.

Discussion:

Although cervical carcinoma associated with HIV/AIDS is common, non HIV/AIDS immune deficient states leading to this condition is exceedingly rare. Cervical cancer associated with immune-deficiency states behaves differently and is more resistant to treatment. Furthermore, it is suggested that some form of selective immune deficiency (to HPV) is associated with most cases of squamous cell cervical cancer. Weak or absent immune response to E2 & E6 antigen of HPV was demonstrated in patients of cervical cancer despite good general immune status. Proper identification of the specific type of immune deficiency to HPV may offer the prospect of more vigilant screening for cervical dysplasia. Understanding the role of the immune system in the progression of HPV infection may help in the fight against cervical cancer.

ISOLATED LEFT ANTERIOR DESCENDING ARTERY VASCULITIS IN A POSTPARTUM WOMAN.

Rajesh Ramineni, MD, Associate, Preeti Misra, MD, Associate, Rashad Khazi Syed, MD, Associate, Syed Mahmood, MD.

Department of Medicine, Sinai-Grace Hospital, Wayne State University/ Detroit Medical Center, Detroit, MI.

Introduction:

Postpartum period is frequently associated with various inflammatory processes in vasculature. Several case reports suggest high incidence of arteriopathy in cerebral vessels and spontaneous coronary artery dissection in postpartum women as compared to the normal population. However, single coronary artery involvement with sparing of all other major vessels in the body has never been reported.

Case Report:

A 33 year old G1P1A0L1 African American female, who had a normal vaginal delivery a week ago, was admitted to hospital with complaints of chest pain associated with elevated troponins and T wave inversion in leads V5 and V6. Patient denied any significant medical problems except for pregnancy induced hypertension. Cardiac catheterization (CC) revealed normal coronaries with an ejection fraction (EF) of 55-60% and was managed medically. She was readmitted within 24 hours after discharge with similar complaints and was found to have a non-ST- elevation myocardial infarction. Cardiac MRI did not show any evidence of myocarditis. CC was repeated when her troponins were increasing despite medical management and it showed diffuse narrowing of the Left anterior descending artery (LAD) without involving other coronaries and an EF of 20-25%. ESR and C-reactive protein were elevated and rest of the work up for vasculitis was negative, including MRA of head, neck, thorax and abdomen. She responded to steroids and she was asymptomatic with an EF of 40% at the time of discharge.

Discussion:

We are reporting the first case of isolated coronary artery vasculitis of unknown etiology. This case illustrates that postpartum patients presenting with typical chest pain and elevated troponins should raise suspicion of vasculitis of coronary arteries although, the incidence of spontaneous coronary artery dissections is higher during peripartum period. In conclusion, vasculitis can be an important cause of typical chest pain in postpartum period which needs prompt diagnosis and can be managed very easily with steroids.

THROMBOCYTOPENIA AND RINGED SIDEROBLASTS IN A PATIENT WITH 5Q DELETION

Sonali Sud MD, Associate; Preeti Misra MD, Associate; Leopoldo Eisenberg MD FACP, Clinical Associate Professor of Medicine, Wayne State University; Department of Internal Medicine (Hematology/Oncology), Sinai Grace Hospital, Detroit, MI

Introduction

5q- Syndrome is a myelodysplastic syndrome characterized by refractory macrocytic anemia, normal to high platelet counts and preserved WBC counts. Neither thrombocytopenia nor ringed sideroblasts are usually found in association with it. A case series presented by Mathew et al of 43 patients with 5q- reported 7% had refractory anemia with ringed sideroblasts (RARS), and 18% had platelets <150,000. Thrombocytopenia with 5q- has been reported in 6 children by Pitman et al. Here we report a previously unreported association of 5q-, RARS and thrombocytopenia.

Case Report

A 76 year old female with history of breast cancer 14 years back treated with combination chemotherapy (Adriamycin/Cytoxan), CHF, and atrial fibrillation was referred for new onset thrombocytopenia. At that time, blood work revealed a platelet count of 63,000. Past records showed a platelet count of 156,000. Physical examination revealed no pallor, icterus, ecchymosis, petechiae or splenomegaly. CBC revealed WBC count of 3900, hemoglobin 8.4, MCV 88.9 and platelet count 55,000. Peripheral smear showed decreased WBCs, anisopoikilocytosis, decreased platelets and giant platelets. A bone marrow aspiration and biopsy was done to evaluate this evolving pancytopenia. Bone marrow was hypercellular, with dyserythro, dysmegakaryopoeisis, 13% ringed sideroblasts, and no increase in blasts. Cytogenetics revealed a predominant 5q-, along with some other consistent chromosomal abnormalities.

Discussion

This case brings to our attention many new facts in association with what is known about MDS. First, the presence of thrombocytopenia and ringed sideroblasts with 5q- syndrome does not fit with the current classification of MDS. Also, treatment with alkylating agents, which this patient underwent, can predispose to developing 5q-. The question arises of whether such treatment may impact the blood picture in patients that do develop 5q-. Another thought is do patients who have complex chromosomal abnormalities vs. those with an isolated 5q- have a predisposition to present with such a picture? Finally, the question arises how these factors impact response to treatment with lenolidomide, and the prognosis. Further research in this complex field of myelodysplastic syndrome is definitely warranted, and therefore recommended.

VALUE OF PROPHYLACTIC ANTIBIOTICS IN PROSTATE BIOPSY

Sonali Sud MD, Associate, Sinai Grace Hospital, Detroit Medical Center, Detroit, Michigan

Background: Prostate cancer is the second most common cancer in the United States. The lifetime chance of being diagnosed with prostate cancer is 1 in 6. Diagnosis currently entails a prostate biopsy, with the most common method being TransRectal Prostate Biopsy (TRPB). The overall risk of infectious complications of TRPB is reported to be less than 1% and can range from asymptomatic bacteruria, to urinary tract infection and sepsis. There are currently no guidelines on the use of antibiotic prophylaxis prior to biopsy. This review was conducted to evaluate the effectiveness of antibiotic prophylaxis in reducing the risk of infectious complications following TRPB.

Materials and Methods: A literature search using Medline (1950 to August week 1, 2007) was performed using the search terms ‘Prostate biopsy’, ‘Prostatic biopsy’, ‘Antibiotic Prophylaxis’ and ‘Prophylactic Antibiotics’ to find all Randomized Controlled Trials that compared prophylactic antibiotic use to placebo or no treatment.

Results: We found three studies that evaluated the role of prophylactic antibiotic therapy prior to TRPB, but different endpoints and antibiotics were used in each study. All of the studies demonstrated a significant reduction in the incidence of bacteruria following TRPB, with the number needed to treat (NNT) ranging from 4.7 to 20. There were no significant differences in the efficacy of the different antibiotics.

Conclusions: This review suggests that the use of antibiotics, either fluoroquinolones such as ciprofloxacin/ofloxacin, or TMP-SMX before prostate biopsy may help prevent infectious complications. However, keeping in mind the overall low rate of infectious complications associated with the procedure, the benefits need to be weighed against the risk of increasing antimicrobial resistance before recommending this practice.

A RARE CASE OF SPINAL,PELVIC AND LONG BONE INVOLVEMENT IN OSSEOUS SARCOIDOSIS

Olobatoke A.O, MD, Associate, Venkatram M, MD, Associate, Department of Medicine, Wayne State University/Detroit Medical Centre(Sinai Grace Hospital)Detroit, MI.

INTRODUCTION

Sarcoidosis is a multisystemic non caseating granulomatous disease.

Documented osseous involvement is about 5%. This typically affects the phalanges, ribs and skull in a lytic pattern. Sclerotic lesions however are rare and have predilection for the spine when they occur.

CASE REPORT

A previously healthy 38yr old African American man presented with a one year history of weight loss, night sweats, radicular back pain, limping and no loss of rectal sphincteric tone. A differential diagnosis of myeloma, lymphoma and tuberculosis were considered after physical examination. Radiological work up included X-rays of the spine and extremities, CT scan of the chest and MRI of the spine. Increased density of lumbar spine as well as diffuse signal abnormality in lumbar, sacrum, paraspinal and presacral structures with epidural extension was noted. Mediastinal and paratracheal lymph nodes were biopsied and returned negative for malignant cells. Serum protein electrophoresis was negative for monoclonal immunoglobulin and HIV ELISA was negative.

Interestingly, whole body bone scan revealed increased activity in both right and left tibia appearing as bilateral cortical lytic lesions on MRI and prompted a tibia biopsy which showed a non caseating granulomatous inflammation, negative for malignant cells, acid fast bacilli and fungi.

DISCUSSION

Published literature has described dactylitis particularly in the middle and distal phalanges as the commonest manifestation of bone sarcoidosis. This pattern was however absent in this patient who presented with sclerotic lesions of the spine, pelvic bone and lytic lesions of the long bones mimicking multiple myeloma. Vertebral and long bone sarcoidosis is rare and is diagnostically challenging since it may mimic either lytic or blastic neoplastic lesions, particularly metastases from primary sites like lung or breast cancer.

CONCLUSION

In a nutshell,this case reiterates the diagnostic challenge posed by sarcoidosis due to its variable presentation. A combination of radiological and tissue biopsy is highly recommended to arrive at a diagnosis since radiographic findings alone are non specific. Despite the fact that osseous sarcoidosis is rare, a high index of suspicion is needed to timely detect this entity since it portends an aggressive and poor prognosis in such patients.

EFFICACY OF MRI FOR BREAST CANCER SCREENING IN HIGH RISK WOMEN

Ramchandani Harsha MD, Associate; Munasinghe R, Fellow; Department of medicine, Sinai Grace Hospital, Detroit Medical Center, Detroit, MI.

Introduction- Almost one third (32%) of all cancers diagnosed in women is breast cancer. It’s the leading cause of cancer death among women aged 20 to 59 years. Women at a high risk of breast cancer often develop the disease at an early age. In young women, mammography has low sensitivity because their breast tissue is denser. Use of contrast-enhanced (CE) MRI may improve the detection of cancer in young high-risk group.

Methods- We conducted the review of literature to assess the effectiveness of adding MRI to mammography in screening this population. Database searched were Pubmed and Ovid. Search Terms used were breast cancer screening, MRI, mammography and high risk women. Study inclusion criteria were reasonable number of study subjects, randomized and prospective studies.

Study Results - We found six studies that met out search criteria. All six studies showed that adding MRI improves the sensitivity of detecting breast cancer (sensitivity range: 77-100%) compared to mammography (16-40%) alone. This leads to an incremental increase of 8.2–24.7 cancers per 1000 screened. Specificity with MRI (range: 81-99%) in the six studies was less than mammography (range: 93-99%) and resulted in a 3-5 fold higher rate of patients been recalled for additional investigation of false positive results. One study compared the characteristic of tumor detected by MRI with two age matched control groups screened by mammography. Tumors <10 mm in diameter were significantly greater in surveillance group (43.2 percent) than in either control group (14.0 percent [P<0.001] and 12.5 percent [P=0.04], respectively). None of the studies evaluated the impact of adding MRI on breast cancer mortality.

Conclusions: Breast magnetic resonance imaging (MRI) has been proposed as an additional screening test for young women at high risk of breast cancer in whom mammography alone has poor sensitivity. Only limited data is available on the cost-effectiveness of breast MRI screening.

Tranformation of a long standing Essential thrombocythemia to Polycythemia Rubra Vera.-Role of JAK-2 V-617 Positivity.

Dr A.Saste MD, Associate/ S.Jindani MD, Associate/Dr P.Misra MD, Associate/Dr Leopoldo Eisenberg FACP, Clinical Associate Professor. Dept. of Medicine: Sinai Grace Hospital, Wayne State University, MI.

Introduction:

Essential thrombocythemia (ET) and Polycythemia Rubra Vera (PRV) are both chronic myeloproliferative disorders characterized by a polyclonal hemopoetic stem cell proliferation.The transformation of ET to PRV is an extremely rare phenomenon.We report such a transformation.

Case Report:

A 63 year old male on routine laboratory evaluation in 1997 was found to have a platelet count of 535,000/cmm,WBC of 10,800/cmm and RBC of

5.32 million/cmm. Reactive causes of this patients thrombocytosis were ruled out. A bone marrow biopsy confirmed the diagnosis of essential thrombocythemia and the patient was started on Aspirin. The patient’s clinical and hematologic course remained stable over the next 10 years.In 2005 with the arrival of JAK-2 mutational analysis the patient was found to exhibit a JAK-2 V-617 mutation. In 2007, on routine medical follow up the patient was found to have a WBC of 23,100/cmm, RBC of 6.38 million/cmm, Platelet count of 667,000/cmm, Hematocrit of 54.1%, serum Erythropoetin level of 2 units (low) and a marked splenomegaly. Secondary causes of the patient's newly developed polycythemia were ruled out. A bone marrow biopsy showed trilinear hyper proliferation, low reticulin fibrosis and exhausted marrow iron stores,findings consistent with a diagnosis of PRV.

Conclusion:

ET usually runs an indolent course with a median survival exceeding 20 years.Leukemic, polycythemic, or fibrotic disease transformation in essential thrombocythemia is an infrequent occurrence with a 15-year cumulative risk of approximately 5% or less in each instance.ET with JAK 2 V617 (+) subtype has been shown to later develop into a PRV. Thus JAK 2 V617 (+) ET should be monitored with careful laboratory and clinical follow-up for the development of PRV. Whether we can thus imply that JAK 2 V617 (+) ET has a poorer prognosis than its JAK 2 V617 (–) counterpart calls for further studies into the long term course of these two subtypes,which may bring about further changes in the current classification of chronic myeloproliferative disorders.

References:

1)Essential thrombocythemia: scientific advances and current practice.Myeloid disease:Current Opinion in Hematology. 13(2):93-98, March 2006.Tefferi,Ayalew.

2)JAK-2 mutation in ET:clinical associations and long term prognostic relevance:A. Wolansky et al.BJH,131,208-213:2005 Blackwell publishing.

THYROTOXIC PERIODIC PARALYSIS (TPP)

Kamalakar Nerusu, MD, Associate, Rama Nadella, MD, Associate, Rajika Munasinghe, MD, Member, Opada Alzohaili, MD, Member,

Department of medicine, Sinai Grace Hospital, Detroit Medical Center, Detroit, MI.

Introduction:

Hypokalemic Periodic Paralysis (HPP) is a heterogeneous group of metabolic disorders. Primary HPP is caused by mutations in the ionic channel genes and is usually transmitted in an autosomal dominant pattern. This should be distinguished from HPP secondary to other causes such as hyperthyroidism, diuretic use and Conn’s syndrome. Thyrotoxic periodic paralysis is usually associated with Graves' disease and is mostly seen in Asian patients. Male to female ratios have been reported to range from 17:1 to 70:1.

Case Report:

A 24 year old Korean female presented to the hospital after a fall due to sudden onset of weakness of her the legs. She had similar symptoms 4 months ago that were less severe and followed by complete spontaneous recovery. There was no history of trauma, strenuous exercise, recent infection or any medication use. Physical examination was unremarkable except for weakness. Her initial laboratory studies showed a serum potassium of 2.2, TSH of 0.03(n=0.34-5.00), free T4 of 5.19 (0.60-1.50) ng/dL and total T3 of 522 (87-190) ng/dL. She also had elevated Thyroid microsomal Antibodies >1000 (Reference range <40). She was treated with potassium supplementation and Propylthiouracil for 3 weeks followed by Radioactive Iodine Ablation with complete resolution of her symptoms.

Discussion:

This case illustrates that hyperthyroidism can precipitate hypokalemia which in turn can lead to thyrotoxic periodic paralysis (TPP). The majority of cases of hyperthyroidism associated with TPP are due to Graves’ disease. TPP is a common complication of hyperthyroidism in Asian men but is increasingly seen in Western countries. It is characterized by proximal muscle weakness, paralysis and hypokalemia due to a massive intracellular shift of potassium. Hypokalemia is the hallmark of TPP. Attacks are commonly precipitated by ingestion of carbohydrate-rich meals, alcohol, or strenuous exercise. During periodic paralysis immediate potassium supplementation should be done to prevent cardiopulmonary complications. The diagnosis at initial presentation is often delayed because of the subtleness of the clinical features of thyrotoxicosis. Thyroid function should be evaluated in patients with hypokalemic paralysis to distinguish TPP from other forms of hypokalemic periodic paralysis and also treating thyrotoxicosis will prevent further attacks.

Unusual Presentation of Laryngeal Carcinoma

Naushaba I Khalid, MD, Associate; Naga V A Kommuri MD, Associate; Munasinghe Rajika MD

Department of Internal Medicine, Sinai-Grace Hospital/Detroit Medical Center

Introduction:

Case Report:

Discussion:

Idiopathic Esophageal Ulcer In A Patient With AIDS.

Chadi Saad, MD, Member, Abu Fazal Shaik Mohammed, MD, Associate, Department of Medicine, Sinai-Grace Hospital, Detroit Medical Centre , Detroit, MI.

Introduction:

Esophageal ulceration is a common and important cause of morbidity in patients with acquired immunodeficiency syndrome (AIDS). After known causes are excluded, a subgroup remains with unexplained esophageal ulceration, known as idiopathic esophageal ulceration (IEU). Diagnosis of this entity is vital as treatment for fungal or viral causes involves potentially toxic antimicrobial therapy whereas IEU is treated with steroids.

Case Report

We present a case of a 44 year old woman with a past medical history of HIV diagnosed 12 years ago, was evaluated for complaints of fever, epigastric pain and difficulty in swallowing, which was progressing over the past week,. The patient was not compliant with her medications, and had stopped HAART therapy one year ago. On examination she had diffused oral trash up to the back of her throat involving the tongue. Her lab results revealed that her CD4 count was 45, viral load was more than 100,000. The patient was initially treated for oral and possible candidiasis with fluconazole and nystatin, but she did not show any improvement with this treatment. Upper GI endsocopy revealed multiple punched out giant ulcers involving the distal half of the esophageous with normal study for stomach and proximal part of small bowel. The Histopathology study showed acute inflamation with fibropurulent exudate, CMV and HSV were negative on immunostain and also no fungi were detected. The patient was then started on oral prednisone. After the start of steroid therapy the patient showed significant improvement in her symptoms and at the time of her discharge she was able to tolerate oral diet. She was discharged on a 6 week course of steroid therapy.

Discussion:

The pathogenesis of Idiopathic Esophageal Ulcers is still unclear. It has been found in some patients that electron microscopy demonstrated retroviral-like particles at the ulcer site. The proposed theory involves a role for apoptosis in the pathogenesis of IEUs by a mechanism involving HIV-associated bystander killing of uninfected mucosal cells. Potential factors in development of these ulcers include: high-titer viremia, inflammatory cytokine stimulation, and altered GI immunopathophysiology. These ulcers do not respond to empirical antiviral or antifungal therapy, but do respond to immunosuppressive drugs, suggesting that that they are immune mediated. The current therapy of IEU includes corticosteroids or, less frequently, thalidomide, misoprostol and viscous lidocaine. As shown above it is of atmost importance to diagnose IEU for the optimal treatment.