PROBLEMA DE INVESTIGACIÓN: LAS DEFICIENCIAS QUE EXISTEN EN LOS MODELOS DE RESPONSABILIDAD EMPRESARIAL EN LAS
2.2. Marco Doctrinario
2.2.2 Impactos ambientales de la minería
with methylated spirit while the patient was lying or sitting in a comfortable position depending on the site of lymph node to be aspirated.
A disposable 21G needle mounted on 5ml syringe was inserted into the lymph node, steadied by the index finger and thumb of the other hand.
The plunger was withdrawn and aspiration effected with needle moving back and forth in various directions through the tissue of the lymph node until aspirate appeared at the base of the needle; then the vacuum was released very slowly and the needle removed form the node. Gentle pressure with the pulp of the finger on a dry swab was then applied over the site of puncture for few minutes to prevent overt bleeding haematoma formation. Thereafter the needle was separated from the syringe; air drawn into the barrel; the needle reconnected, and the contents “blown out”
onto a glass slide and gently smeared.
Aspiration was repeated until 4 slides were smeared from every patient in order to increase the yield, Two of the slides were wet-fixed immediately by immersion in 95% ethyl alcohol in a coplin jar for at least 30 minutes, the remaining two slides were air dried. Standard Haematoxylin and Eosin or the Papanicolaou staining method was used to stain the wet-fixed smears. The air-dried slides were stained by the May-Grunwald Giemsa (MGG) method. The slides were read by one experienced cytopathologist assigned for the study using binocular light microscope (Olympus). All the cytological and histological studies in the catchment areas are carried out in the department of pathology UCTH. This Centre therefore formed the base for processing of specimen in this study.
Excision biopsy of accessible and representative lymph nodes followed under standard aseptic technique in the casualty or main theatre under local or general anaesthesia as was adjudged appropriate; with extreme care to prevent trauma to the node. This was followed by routine paraffin section histology to confirm or establish the diagnosis.
Along with the above. Full blood count (FBC), Erythrocyte sedimentation rate (ESR) and HIV screenings were done using the lmmuno Comb II technique. Mantoux test was done only on those suspected to have tuberculous lymphadenitis.
The results were subject to statistical analysis. Specificity and sensitivity was determined using the statistical method for determination of Diagnostic Accuracy after Malone et al 61 Thus:
POSITIVE NEGATIVE
POSITIVE A B
NEGATIVE C D
Diagnostic Sensitivity = A A + C Diagnostic Specificity = D
B + D False-Positive Rate = B
A + B
False-Negative Rate = C
C + D
Positive Predictive Value = A A + B Negative Predictive Value = D C + D
Overall diagnostic accuracy = A + D A+B + C+D
FIGURE 1
FNAB OF AXILLARY LYMPH NODE
FIGURES 2 & 3
CHAPTER FOUR
RESULTS
The duration of study was 2 years (January 1999 to December 2000). Total number of peripheral lymph node examined by fine needle aspiration cytology and by excision biopsy was 205. Out of these, 84 (40.98%) were males and 121 (59.02%) were females giving M:F ratio of 1:1.44. Ages ranged from 6 years to 86 years.
Forty-one (41) cases had cytology done, but could not have the follow-up histology of the lymph nodes due to various reasons and were excluded from the study.
The grouping of lymph nodes assessed according to anatomical sites were as shown in Table 1:
TABLE I: ANATOMICAL SITE OF BIOPSIED LYMPH NODE
LOCATION NO. %
Cervical (Head & Neck) 95 46.3
Axillary 89 43.4
Groin 20 9.8
The quality of smears as categorized by the reporting pathologist are contained in Table 2 below. The overall quality of the slides in terms of adequacy for diagnosis or otherwise is shown in the pie chart of Figure 4 below.
TABLE 2: QUALITY OF SLIDES
Slide Description No. %
Satisfactory smear 168 81.9
Haemorrhagic hypocellular smear but adequate for diagnosis
18 8.8
Poorly prepared and inadequate for diagnosis
7 3.4
Inadequate for diagnosis (Accellular or unsatisfactory smear)
12 5.9
TOTAL 205 100
FIGURE 4: PIE CHART
Showing the Distribution by percentage of the quality of smears.
90.7%
(186)
Key:
9.3%
(19)
Satisfactory smear for diagnosis
Unsatisfactory smear for diagnosis
Classification according to pathology by both FNAB result and histology is as shown in Table 3:
TABLE 3: FNAB (CYTOLOGY) VS HISTOLOGY IN DIAGNOSIS PATHOLOGY CYTOLOGY HISTOLOGY
Malignancy 92 (44.9%) 106 (51%)
Reactive hyperplasia 95 (46.3%) 81 (39.5%) Tuberculosis (Granulomatous)
Disease 6 (2.9%) 18 (8.8%)
No Diagnosis (Unsatisfactory
smear) 12 (5.9%) -
TOTAL 205 205
Out of 205 cases, 106 (51%) were diagnosed as malignancy by histology, while 92 cases (44.9%) were diagnosed malignant by cytology.
Eight cases were reported as suspicious for malignancy by FNAB, but all were confirmed to be malignant by histology. There was no false positive case in the malignant series. False negative for malignancy by cytology was 14. Final histology diagnosis showed that out of 106 malignant lymph node diseases, 84 (79%) were due to metastasis while 22 (21%) were due to primary lymph node malignancy caused by lymphoma.
Eighteen (8.8%) cases were diagnosed as Tuberculosis (chronic granulomatous disease) by histology while 6 (2.9%) were diagnosed as Tuberculosis by cytology. False positive in this series was 1 and false negatives were 12.
Diagnosis could not be made by cytology in 12 cases (5.9%) due to unsatisfactory smears. Unsatisfactory smears were caused by haemorrhagic sampling, scanty cellularity or poor slide preparation. These were therefore considered false-negatives.
The sensitivity, specificity, false positive rate, false negative rate, positive predictive value, negative predictive value and overall diagnostic accuracy, for the various pathologies were calculated from the above data using the formula of Malone et al.61 These are reflected in Table 4. (The calculations are shown in appendix 3).
TABLE 4: DIAGNOSTIC ACCURACY OF FNAB
PATHOLOGY SENSITIVITY SPECIFICITY FPR FNR PPV NPV ODA
Malignancy 86% 100% 0% 12% 100% 87% 93%
Reactive hyperplasia
99% 89% 15% 1% 85% 99% 93%
Tuberculosis 33% 99% 14% 1% 86% 94% 94%
Overall 87% 97% 8% 6% 92% 94% 93%
KEY:
FPR = False Positive Rate FNR = False Negative Rate PPV = Positive Predictive Value NPF = Negative Predictive Value ODA = Overall Diagnostic Accuracy
Final analysis of the results, which is the combination of all 205 cases, including those slides that were not adequate for diagnosis, gave the overall sensitivity of 87%, specificity of 97%, false positive rate of 8%, false negative rate of 6%, positive predictive value of 92%, negative predictive value of 94% and an overall diagnostic accuracy rate of 93%.
The human immunodeficiency viral (HIV) status was positive in 41 patients (20%) out of 205. The prevalence by disease entities were:
malignant lymph nodes 12.3% (13 of 106), reactive hyperplasia 28.4% (23 of 81 case) and Tuberculosis 27.8% (5 of 18 cases).
During the study, positive changes took place in the Department of Histopathology in the University of Calabar Teaching Hospital notably:
1. A separate cytology laboratory (two rooms) was set up for aspiration of lumps and processing of slides.
2. The time from submission of specimen to readiness of the result was greatly reduced from 2 - 3 days to 1 day on the average. It is now possible to obtain cytology results the same day, if specimens are submitted before or by 12 noon.
FIGURES 5 & 6
CYTOLOGY OF METASTATIC BREAST CANCER
HISTOLOGY OF METASTATIC BREAST CANCER
FIGURES 7 & 8
CYTOLOGY OF LYMPHOMA
FIGURES 9 & 10
CYTOLOGY OF REACTIVE HYPERPLASIA
HISTOLOGY OF REACTIVE HYPERPLASIA
DISCUSSION
The University of Calabar Teaching Hospital (UCTH) is a tertiary institution with an established histopathological laboratory. At the time of this study there were four consultant pathologists in the department. This hospital was the only hospital in Akwa Ibom and Cross River States of Nigeria with the capability for histopathological examination of tissues. The catchment area is large and the inclusion of patients from other major health institutions around Calabar, makes the result of this study fairly representative of Calabar and its environs.
Calabar is one of the centres in Nigeria with a cancer registry, thus the establishment of an efficient cytology laboratory is therefore a very important development in the health care delivery system of this region of Nigeria.
This study shows that lymph node biopsy for diagnosis is a common procedure in the UCTH. The results show that malignant lymphadenopathy in head and neck and axillary regions of the body is the commonest cause of lymph node enlargement in Calabar, which requires diagnostic assessment. Acute suppurative lymph node enlargements are commoner in the inguinal region and usually diagnosed without the need for cytology or histology as the primary cause is often very obvious.
node for histological assessment was obtained from axillary sampling during surgical treatment. By so doing, double operation was avoided in that subgroup. The axilla was the commonest lymph node site sampled for cancer of the breast.
The Cervical region contributed 95 cases (45.3%) to the sample size. This may not be of much statistical significance because that site was preferred in most cases of generalized lymphadenopathy. This choice was made because of the ease of access and good representation of nodes in the neck as insignificant cervical lymphadenopathy is uncommon. Inguinal lymph nodes were deliberately avoided because nonspecific hyperplasia is very common even in normal subjects. This is in keeping with the findings of Ramzy et al,62 who sampled 103 aspirates from 100 patients and reported that 98.3% were from the head and neck region.62
The quality of slides was satisfactory for most diagnosis and compares favourably with other reports.44,57,62,63 Unsatisfactory slides constituted 8.7% in this study and were due to haemorrhagic and/or hypocellular smears as well as poor handling. This is considered acceptable because lymph nodes are highly vascular. The use of lower suction pressure in 5ml syringe is considered suitable by the author for lymph node aspiration to avoid a large number of haemorrhagic smears in such highly vascular tissue with loose architecture. Higher suction pressure in 10ml and 20ml syringes would be suitable for more solid tissues as recommended by other workers.3,30 Unsatisfactory aspirates have been reported in various studies in the ranges of 3.9 – 15%. 62,63
Malignancy is the commonest cause of axillary and cervical lymphadenopathy accounting for 106 (57%) in this study. Reactive hyperplasia followed closely, 81 (39.5%). This figure may be different when all anatomical sites are considered with equal number of node sampling. Lymphoma, breast cancer, nasopharyngeal cancer and parotid tumour were the common primary sites. Most patients were adults in the cancer age group (above 40 years). Ramzy et al found only 4.9%
malignant lymph nodes in the head and neck region out of 103 lymph node aspirates in the 21-year-olds and below.62
The percentage of chronic nonspecific reactive hyperplasia, 46.3%, is consistent with findings by other authors.1,2,62 In children, the leading cause of lymphadenopathy is reactive hyperplasia. Large number of false positive cases in this series was due to presence of nuclear reaction that are seen as blast cells which resemble nuclear atypia of malignancy. Many of the false positive cases were confirmed by histology to be granulomatous infection (TB).
Granulomatous infection formed 8.8%. This low yield is explained by the fact that the common granulomatous infection in Calabar is tuberculosis. The commonest mode of TB presentation is pulmonary.
Tuberculous lymphadenopathy is not so common although more are being seen especially in females and children (7 of the 8 cases seen in this
one of the presentation of this infection. The yield of HIV infection among those with malignant lymph nodes was low 12.3%.
There is significant association of tuberculosis with HIV infection.
Nearly a third (27.8%) of TB lymphadenopathy patients were positive for HIV infection. This demonstrates the possible strong association of TB with HIV infection.
The sensitivity, specificity as well as the diagnostic accuracy obtained in this study, (87%, 97% and 93% respectively) compares very satisfactorily with findings in other centres.8,10,33,49,62
The malignant lymph node pathology gave the highest sensitivity (100%) and the highest positive predictive value (100%). This means that a diagnosis of positive for malignancy from FNAB is adequate in taking a decision for management without further need for histology. This is consistent with other reports. Sensitivity of 86% and false negative rate of 12% indicate the need for follow-up biopsy and histology of negative lymph node cytology if malignancy is suspected. Ultrasound, computerised tomography and other imaging guidance could extend the benefit of diagnostic FNAB to deep seated lymph node assessment of cancer patients and other lymph node pathologies in Calabar.
The lowest specificity and positive predictive values (89% and 85%) respectively) were obtained in reactive hyperplasia. This is indicative of the heterogeneous causes of this pathology. The highest false positive rate (15%) was also seen in this group.
FNAB of Tuberculous lymph nodes gave the lowest sensitivity (33%). This shows the relative inadequacy of FNAB as a tool for the diagnosis of TB in Calabar presently.
CONCLUSION
Peripheral lymphadenopathy is a common clinical problem in Calabar. The development of a quick, safe and accurate diagnostic modality is important in the management of such patients in this environment.
The overall sensitivity (87%), specificity (97%) and diagnostic accuracy (93%) of lymph node FNAB and cytology in Calabar is high and good enough to generate confidence in its use for diagnosis especially in malignancies. This is in keeping with literature.8,10,33,49,62
HIV infection is an important differential diagnosis of persistent peripheral lymphadenopathy (20%) in this study. HIV screening test is considered appropriate on all such patients, especially when malignancy is not likely. There is strong association of reactive lymph node hyperplasia and TB lymphadenopathy with HIV infection.
During FNAB of breast cancer and other peripheral tumours, the pre-operative sampling of associated regional lymph node by FNAB for cytology was useful in the definitive clinical staging and the pre-operative planning of tumour management. It also obviated the need for intra-operative frozen section histology.
This study significantly improved the speed of diagnosis, skills and competence of relevant workers as well as facilities for FNAB and cytological diagnosis in UCTH, Calabar. It therefore played a significant positive role and high clinical value in the management of patients with tumours and persistent peripheral lymphadenopathy in South-South Nigeria.
RECOMMENDATIONS
1. Based on the results from this study, fine needle aspiration biopsy and cytology is recommended for use as a first line tool in the diagnosis of persistent peripheral lymphadenopathy in Calabar, especially when malignancy whether metastatic or primary is suspected.
2. During FNAB for breast cancer and other peripheral tumours, all associated regional lymph node enlargements, should equally be sampled by FNAB for cytology. This will help in the pre-operative planning of tumour therapy and may obviate the need for intra-operative frozen section.
3. HIV screening test should be carried out on all patients, with lymphadenopathy.
4. The use of 5ml instead of 10ml or 20ml syringe for lymph node FNAB is recommended because of its loose tissue architecture and high vascularity. This will reduce the chances of haemorrhagic smear.
5. Future work on FNAB of TB lymphadenopathy is recommended so as to improve the sensitivity and specificity as well as establish its role in the diagnosis.
6. Cytology laboratories should be established as separate unit of
APPENDIX 1
PROTOCOL FOR PATIENT SELECTION
LYMPHADENOPATHY
History, Physical Examination
- Ulcer or Acute - No Abscess or ulcer
Pyogenic infection - Generalized lymphadenopathy
- Transient Lymphadenopathy - Cervical and/or axillary only - Only groin and < 1months - Only groin and > 1 months
- Refuse consent - Other Diseases
- Consent
EXCLUDE INCLUDE
INITIAL INVESTIGATION
& FNAB
Lymph Node Biopsy
YES NO
NO YES
APPENDIX II PROFORMA FOR DATA
1. PERSONAL DATA OF PATIENT:
(e) Name:………..
(f) AGE:………..
(g) SEX:………..
(h) ADDRESS:………
(i) TRIBE:……….………..
(j) HOSPITAL NUMBER:……….
2. HISTORY AND PHYSICAL EXAMINATION:
(a) History:……….
………..
………..
(b) Physical Examination:………
………..
………..
(c) Clinical diagnosis:………...
3. INVESTIGATIONS:
(a) Full Blood Count:………
(b) Erythrocyte Sedimentation Rate:……….
(c) Mantoux Test:……….
FNAB for cytology and Cytological Diagnosis:………
APPENDIX III
DIAGNOSTIC ACCURACY OF LYMHPNODE CYTOLOGY
MALIGNANCY Positive Negative
Positive 92 0
Negative 14 99
Sensitivity 92
92 + 14 = 86%
Specificity 99
0 + 99 = 100%
False positive rate 0
92 + 0 = 0%
False negative rate 14
14 + 99 = 12%
Positive Predictive value 92
92 + 0 = 100%
Negative Predictive value 99
14 + 99 = 87%
Overall diagnostic accuracy 92 + 99
92+0+14+99 = 93%
REACTIVE HYPERPLESIA
REACTIVE HYPERPLESIA
Positive Negative
Positive 81 14
Negative 1 112
=
=
=
=
=
=
=
=
Sensitivity 81
81+ 4 = 99%
Specificity 112
14 + 112 = 89%
False positive 14
81 + 14 = 15%
False negative 1
1 + 112 = 1%
Positive Predictive value 8
81 + 14 = 85%
Negative Predictive value 112
1 + 112 = 99%
Overall diagnostic accuracy 81 + 112
81+14+1+112 = 93%
TUBERCULOSIS
TUBERCULOSIS Positive Negative
Positive 6 1
Negative 12 187
Sensitivity 6
6 + 12 = 33%
Specificity 187
1 + 187 = 99%
False positive 1
6 + 1 = 14%
False negative 1
1 + 112 = 1%
=
=
=
=
=
=
=
=
=
=
=
OVERALL DIAGNOSTIC ACCURACY
OVERALL Positive Negative
Positive 179 15
Negative 27 398
Sensitivity 179
179 + 27 = 87%
Specificity 398
15 + 398 = 97%
False positive 15
179 +15 = 8%
False negative 27
27 + 398 = 6%
Positive Predictive value 179
179 +15 = 92%
Negative predictive value 398
27+398 = 94%
Overall diagnostic accuracy 1 79 + 398
179+15+27+398 = 93%
=
=
=
=
=
=
=
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