effusions explored

M1 UNITDR.G.KANNAN

PROF.RUKMANI REDDY

EFFUSIONS EXPLORED

CASE 1

HISTORY:

Hemavathy 65/F not a known HT/DM/CAD/COPD.H/O Breathlessness 3 days, insidious onset,

progressive in nature , worsened over past 4 hrs. Preceded by NSAID intake for flu –like symptoms.Associated with decreased urine output , swelling

of face & legs.Patient was treated in a private hospital with

inj.lasix & Tab.nifedipine and referred to SGH.No other significant positive history.

EXAMINATION:

Conscious , Oriented , afebrile.Dyspnic , tachypnicpallor+B/L pitting pedal edema+JVP elevatedPulse-102/minBP-180/110 mmhgCVS-S1S2 heardRS-B/L crepitations +,BS↓ both bases.P/A-soft.

CONTD…………..

ECG-T inversion L II,L III,AVF

CHEST XRAY-Cardiomegaly , b/l pleural effusion , congestive lung fields

IMPRESSION

HT

ACUTE LVF

TO R/O ACUTE ON CHRONIC KIDNEY DISEASE.

TREATMENT:Backrest

Nasal O2

I.V.Dieuretics

Antihypertensives

INVESTIGATIONS:

Hb -10.5 g/dlTC -8200DC -P60,L37,E3ESR -5/11PLC -2.0 LacksURINE albumin-+ sugar -nil dep-4-6 epi cells

CONTD………….RBS-146 mg/dlUREA-22CREATININE-0.9Na-130 meq/lK-3.1 meq/lSERUM bil-1.0 mg (D)-0.3AST -45 UALT-37 USAP-92 USERUM PROTEINS -5.6 ALBUMIN-3.6

CONTD………

USG ABDOMEN-post –menopausal status of uterus.

ECHO -NO RWMA normal LV systolic function

REVIEW:

Patient improved marginally but continued to be dyspnic.

CT CHEST (P)-B/L PLEURAL EFFUSION CAUSING COLLAPSE OF UNDERLYING LUNG PARENCHYMA

CT-CHEST:

PROBLEMS:

DYSPNEAHYPERTENSIONNORMAL ECHOB/L PLEURAL EFFUSIONANEMIAHYPONATREMIAHYPOKALEMIA

PLEURAL FLUID ANALYSIS:

PROTEIN-1.3SUGAR-113CELLS-Few lymphocytesCYTOLOGY-reactive effusionAFB-negativeGRAM STAIN-negativeADA-5.52 U/L

CONTD………..24 HRS URINARY PROTEIN-110 mg/day

F T3-1.99 pg/ml(2.30-4.2) FT4-0.83 ng/ml(0.8-2.0) TSH-29.4 MIU/ml(0.35-5.5)

RF,CRP, ANA-negative

DIAGNOSIS:

SYSTEMIC HYPERTENSION

HYPOTHYROIDISM

TREATMENT:

Thyroxin replacement

Antihypertensives

FOLLOW UP

BEFORE TREATMENT AFTER TREATMENT

PATIENT

BEFORE AFTER

TFT

BEFORE AFTER

-F T3-1.99 pg/ml(2.30-4.2)

-FT4-0.83 ng/ml(0.8-2.0)

-TSH-29.4 MIU/ml(0.35-5.5)

-FT3-2.6 pg/ml

-FT4-1.8 ng/ml

-TSH-4.6 MIU/ml

MANIFESTATIONS OF HYPOTHYROIDISM

CARDIAC RESPIRATORYBradycardiaHypertensionPericardial effusionPulmonary

hypertensionQT prolongation Ventricular

arrhythmiasCardiomyopathyCardiac failure

Pleural effusionImpaired

respiratory muscle function

Decreased ventilatory drive

Sleep apnea

CASE 2

HISTORY:

Shanthi 20/F admitted with C/O breathlessness since 1 month.

-insidious onset -slowly progressive -grade III/IV -no orthopnea/PND -no chest pain/syncope/palpitations -cough with minimal expectoration+-associated with systemic symptoms like low

grade fever , myalgia , arthalgia ,loss of appetite & weight×3 months.

-one episode of GTCS.

O/E:

Conscious , oriented , afebrileThin & ill-nourishedSparse hairDry scaly skinHyper pigmented rash around both elbowsPallor+Pedal edema+

Contd………..

Pulse-80/minBP -100/70 mmhgCVS-S1S2 heardRS - B/L basal crepitations+P/A- palpable liverCNS- generalized muscle tenderness+

Contd……..ECG-low voltage complexes

CHEST X-RAY-cardiomegaly.

USG ABDOMEN- hepatomegaly , minimal free fluid in the abdomen , significant pericardial effusion.

CT BRAIN-normal study

PROBLEMS:

Pericardial effusionSystemic symptomsAlopeciaSkin rashArthalgiaSeizures

IMPRESSION:

SLETO R/O TUBERCULOSIS

INVESTIGATIONS:Hb-8 gm/dlTC-7100DC-P60 , L40ESR-8/15PLC-1.82 lacksRBS-124UREA-29CREATININE-0.7Na-138K-4.3

CONTD……..LFT: -serum bilirubin-0.8 - (D)-O.3 -AST -24 -ALT -36 -SAP -84 -SERUM PROTEINS-5.6 - ALBUMIN-3.2

CONTD…..

HIV- non-reactiveMANTOUX-negativeFT4-0.96 ng/dlTSH-13.7324 hr URINARY PROTEIN-170 mg/dayANA-++++ds DNA+APTT-31.2 sec(T),30.2 sec(C)

Contd………ECHO-RA/RV dilated LA/LV normal mild TR TRPG-52 PHT-moderate large pericardial effusion no tamponadePERICARDIAL FLUID: -protein:2.9 -sugar :124 -cells :30(90% lymphocytes) -ADA :15 U/L

DIAGNOSIS:

SYSTEMIC LUPUS ERYTHEMATOSES

SUB CLINICAL HYPOTHYROIDISM

ASSOCIATED PULMONARY ARTERIAL HYPERTENSION

TREATMENT:

-Steroids-Antibiotics-Low dose diuretics- Thyroxin replacement

Patient was taken over by rheumatology GH.

PERICARDIAL EFFUSION IN SLEMost common cardiac abnormality- pericardial

involvementClinically evident pericarditis 20 – 40 %PE is an infrequent presenting manifestationDiagnosis rests on other signs and positive ANAPericardial fluid is typically an exudateSymptomatic PE often accompanied by pleural effusionPericardial tamponade is rareTreatment ; NSAID for pericarditisCorticosteroids for large effusionsImmunosuppressant for resistant effusions

PHT ASSOCIATED WITH SLERare but potentially life threatening complication of

SLEIncidence 0.5 – 14 %Mortality 25 – 50 % in two years after diagnosisECHO may show RVH even before onset of symptomsVasoconstriction, vasculitis and thrombosis are

implicatedEndothelial dysfunction is evident with high

endothelin levelsRt heart cath with assessment of vascular reactivity

should be done.Treatment – Ca channel blockers,

Prostacyclin ,endothelin receptor antagonists.

Prevalence of thyroid dysfunction in SLE Appenzeller, Simone MD, PhD; Pallone, Ana

T. MD; Natalin, Ricardo A. MD; Costallat, Lilian T. L. MD, PhD

Our patients with SLE had a high prevalence of symptomatic (6.1%) and significantly more subclinical hypothyroidism(11.5%) and positive thyroid auto antibodies (17%). Thyroid auto antibodies may precede the appearance of clinical autoimmune disease. Sjögren syndrome and positive rheumatoid factors were more frequently observed in SLE patients with autoimmune thyroid disease. We believe that, since symptoms of SLE and thyroid disease can be similar, that SLE patients should routinely been investigated for autoimmune thyroid disease.

COMMON LESS COMMON

VitiligoPernicious anemiaAddissons disease Alopecia areataType1 DM

Celiac diseaseDermatitis

herpetiformisChronic active

hepatitisRheumatoid arthritisSLESjogren’s syndrome

HYPOTHYROIDISM AND AUTO IMMUNE DISORDERS

CASE 3

HISTORY:

Fathima 45/F not a known DM , HT ,CAD , PULM KOCHS.

H/O abdominal distension ×2 weaks -insidious onset -progressive -no associated symptoms -No other significant history.

EXAMINATION:ConsciousOrientedAfebrilePallor+I0 C0 E0 LN0PULSE-90/minBP-110/70 mmhgCVS-S1S2 heardRS-NVBS heard

Contd………

P/A -distended -umbilicus flushed with surface - no dilated veins - no organomegaly - free fluid ++

IMPRESSION:

ASCITES FOR EVALUATION

?MALIGNANCY

INVESTIGATIONS:Hb -9.2gm/dlTC -9500DC -P50L45E5ESR -10/22PCV -28RBC -3.1PLC -3.7G/T -B+veP/S -normocytic normochromic

CONTD……….RBS -126mg/dlUREA -26CREATININE-0.9Na -134K -4.2Cl -98.8LFT Bilirubin(T)-0.8 AST -25 ALT -37 SAP -69 Proteins(T)-6.2 Albumin -3.9

CONTD……….CHEST X-RAY:NADECG:WNLUSG abdomen: -massive ascites- no significant abnormality in solid abdominal&

pelvic organs - ECHO:- MVP,AML- Mild MR- No RWMA- Normal LV systolic function

Ascitic fluid analysis:Gross- haemaorrhagicProtein-3.3Albumin-2.9Sugar-83ADA-15U/LCells-50 cells mostly lymphocytesCytology-reactive effusionAFB-negativeGram stain-negativeC/S-no growthSAAG-1.0

CONTD…….

CA 125-1902 U/ml(N<35 U/ml)

CEA -0.393 ng/ml(N up to 5 ng/ml)

CECT ABDOMEN &PELVIS: massive ascites

OGD SCOPY: normal

COLONOSCOPY: normal

CECT ABDOMEN& PELVIS:

PROBLEMS:

Low gradient ascites

Elevated CA-125

Imaging studies not contributory.

OPINION:

MGE-peritoneal carcinomatosis , advised lap. Biopsy.

ONCOLOGY-HPE evidence for malignancy,advised cell block.

SGE-P/R deposits , suggested USG guided peritoneal biopsy.

GYN-P/V :uterus anteverted , cervix normal , POD free.

Contd………

USG –GUIDED PERITONEAL BIOPSY :no e/o malignancy

LAPROSCOPY & BIOPSY: -serosanguinous ,turbid ascitic fluid of

more than 5 L -multiple peritoneal deposits -omentum walled -up like a mass -uterus & ovaries appears normal. -liver appears normal

Contd……….

HPE REPORT(2998/09) of peritoneal biopsy: -sections show fibrocollagenous tissue

with an adjacent neoplasm composed of neoplastic cells arranged in papillary pattern & sheets.

-The cells are round to cuboidal with the presence of nuclear pleomorphism,vescicular nuclei & prominent nucleoli.

-Stroma shows inflammatory cell infiltrate

IMPRESSION: METASTATIC CARCINOMATOUS

DEPOSITS

QUES:

DIAGNOSIS ?

PROGNOSIS?

TREATMENT?

ANS:

CARCINOMA OF UNKNOWN PRIMARY(CUP) -WOMEN WITH PERITONEAL CARCINOMATOSIS

MEDIAN SURVIVAL -18 months.

TREAT AS STAGE 3 OVARIAN CANCER -debulking surgery followed by

taxane & platinum based chemotherapy.

CARCINOMA OF UNKNOWN PRIMARY (CUP)

DEFINITION:

Carcinoma of unknown primary (CUP) is a biopsy-proven metastatic malignant tumour whose primary site can not be identified during pre treatment evaluation including

1)Thorough history and physical exam2)Laboratory and radiographic studies3)Detailed histological evaluation

STANDARD WORKUP FOR CUP:

HaemogramChest x-rayRFTLFTCT abdomen & pelvisMammographyPSA

EPIDEMIOLOGY:

CUP constitutes 2.3% of all cancers in US (SEER 1973-87)

Annual age-adjusted incidence in US is 7-12 cases per 100,000 population

Median age at presentation is 60 years

Slightly more prevalent in males

BIOLOGY:CUP represents a heterogeneous group of

malignancies characterized by:

-Early dissemination in the absence of a detectable primary

-Unpredictable metastatic pattern -Aggressive biological and clinical behaviour

The hypothesis is that the primary tumour either remains microscopic and escapes clinical detection or disappears after seeding the metastasis

CLINICAL MANIFESTATIONS:

Patients usually present with a short history of local findings related to the metastatic sites and constitutional symptoms

Physical exam is often abnormal with effusions, adenopathy, hepatomegaly and other abnormalities related to the involved sites

The majority of patients have multiple metastatic sites.

PATHOLOGY – LIGHT MICROSCOPY

Light microscopy with hematoxylin and eosin stain can identify four main histologic subtypes of CUP

Adenocarcinoma (50%-60%) Poorly differentiated carcinomas (30%) Squamous cell carcinomas (5%-15%) Undifferentiated malignant neoplasm

IMMUNOHISTOCHEMISTRY:

Tumour type

Immunohistochemistry

LymphomaMelanomaHCCBreast cancer

Germ cell tumourNeuroendocrine

tumour

Leucocyte common antigen

S-100,HMB-45Alphafeto proteinEstrogen & progesterone

receptors,BRST-1,gross cystic disease fibrous protein.

Beta-HCGChromogranin,synaptophy

sin,neuron specific enolase

CONTD……….

TUMOUR IHC STAIN

Lung & thyroid ca

MesotheliomaBladder caGastrointestinal caProstate ca

Thyroid transcription factor-1,thyroglobulin

Calretinin,mesothelinURO-III,

thrombomodulinCDX-2PSA

IMMUNOHISTOCHEMISTRY: CK phenotype

CK7-/CK20-

CK7+/CK20-

CK7-/CK20+

CK7+/CK20+

TumorsHCC, liver, lung

(Squamous, small cell), prostate, renal

Biliary and pancreas, breast, cervical, endometrial, lung (Adenocarcinoma), ovarian (non- mucinous), thyroid

Colon, gastric, Merckel cell carcinoma

Biliary and pancreas, ovarian (mucinous), urothelial

CK7+/CK20+

TUMOR MARKERSCommonly used tumour markers (CEA, CA 19-

9, CA 125) are nonspecific and have limited value in the diagnosis of patients with CUP

They may have a role as a prognostic marker and to evaluate response to therapy

Serum HCG and AFP may be used to exclude testicular cancer

Serum PSA can identify cases of prostate cancer

Elevated thyroglobulin in patients with bone metastases suggests occult thyroid primary

Imaging Studies and Endoscopy:Initial evaluation includes chest radiograph

and CT scan of the abdomen/pelvis

The role of chest CT has not been established

Mammogram is indicated in all women with CUP Adenocarcinoma

The experience with PET is limited

Endoscopy is not recommended as a routine work up for asymptomatic patients and should be used according to the clinical presentation

TREATMENT:

Once the diagnosis of carcinoma is established, the main objective is determine whether the patient belong to one of the favourable subsets, for which there is a specific treatment

Favorable subsets:

Women with isolated axillary adenopathyWomen with peritoneal carcinomatosisSquamous cell carcinoma of cervical lymph

nodesMen with bone metastasis ,elevated PSAPoorly differentiated carcinoma with

midline adenopathyNeuroendocrine carcinomaSolitary metastatic site

Women with isolated axillary adenopathy:Lymph nodes should be tested for ER, PR, and HER-2/neu

In cases of negative mammogram, the primary may be seen on MRI or after mastectomy

Prognosis is similar to lymph node positive breast cancer

Mobile lymph nodes (N1) - Treat as stage IIA breast cancer

Fixed lymph nodes (N2) - Treated as stage IIIA breast cancer

MRM + AND chemotherapy ± hormonal therapy/RTNeoadjuvant chemotheray for N2 disease

WOMEN WITH PERITONEAL CARCINOMATOSIS: The germinal epithelium of the ovary and peritoneal

mesothelium share the same embryological origin (mullerian)

Pathologic & lab (elevated CA-125)characteristics of ovarian CA but no primary tumor identified on TVS/ laparotomy.

More common in women with BRCA-1 mutation and may also be seen after prophylactic oophorectomy

Outcomes are similar to ovarian cancer at equivalent stage

Median survival of 18 months.

Patients should be treated as stage III ovarian carcinoma

Surgical debulking followed by chemotherapy

Squamous cell carcinoma of the cervical lymph nodes:Despite aggressive diagnostic approach, the

primary site is not found in the majority of patients

Ipsilateral tonsillectomy is often performed since the primary can be found in 10 to 25% of cases - Small tumours may originate in the deep crypts and not be detected by superficial biopsy

Treat as locally advanced head and neck cancerLow stage (N1) – Surgery RT or RT aloneHigh stage (N2-N3) - Chemoradiotherapy

.

.

Men with bone metastasis , elevated PSA:

Prostate cancer is the most likely diagnosis - Elderly men with Adenocarcinoma of

unknown primary and predominantly blastic bone metastases

- Patients with increased PSA or positive PSA staining on the biopsy specimen despite atypical presentation

Hormonal therapy

Poorly differentiated carcinoma with midline adenopathy

Young males with tumours of predominant midline distribution (mediastinum and retro peritoneum) should be treated as extragonadal germ cell tumours

Cisplatin-based chemotherapy (BEP)

Neuroendocrine carcinoma

IHC usually stains positive for chromogranin or NSE

Patients frequently present with diffuse metastases to the liver or bones

Platinum-based chemotherapy (platinum + etoposide)

Single metastatic site:

Although other metastatic sites may become evident within a short period, some patients may achieve a prolonged disease-free interval with local therapies such as surgery or radiotherapy

Adjuvant chemotherapy may also be considered

Surgery or RT

TREATMENTUNFAVORABLE SUBSETS

With the exception of the favourable subsets, most patients with CUP have a tumour that is resistant to chemotherapy

The prognosis is very poor, with median survival of 2 to 3 months in unselected patients and 6 to 10 months in those enrolled into clinical trials

Patients with good performance status may benefit from systemic chemotherapy

CONCLUSIONS:CUP represents a group of heterogeneous

tumours sharing the unique characteristic of metastatic disease without identifiable origin at the time of initial therapy

Although identification of the primary tumour may provide valuable information regarding both treatment and prognosis, aggressive diagnostic workup is usually of little value and not cost effective

The recommended approach is to pursue a limited diagnostic approach to identify favourable subsets

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