|Year : 2017 | Volume
| Issue : 4 | Page : 205-209
Histological types of soft-tissue sarcomas at the lagos university teaching hospital
Nzechukwu Zimudo Ikeri, Andrea Oludolapo Akinjo, Olugbende O Ajayi, Adekunbiola Aina Fehintola Banjo
Department of Anatomic and Molecular Pathology, Lagos University Teaching Hospital, Lagos, Nigeria
|Date of Web Publication||18-Jan-2018|
Dr. Nzechukwu Zimudo Ikeri
Department of Anatomic and Molecular Pathology, Lagos University Teaching Hospital, PMB 12003, Idi-Araba, Lagos
Source of Support: None, Conflict of Interest: None
Objective: There is scanty data on histologically diagnosed soft-tissue sarcomas in the Nigerian literature. This is due to paucity of facilities for ancillary testing as well as a dearth of specialist soft tissue pathologists. Knowledge however of the common soft-tissue sarcomas is vital for the establishment of an effective sarcoma service. The aim of this study, therefore, was to determine the histological spectrum of soft-tissue sarcomas in Lagos, Nigeria. Materials and Methods: Archival haematoxylin and eosin (H and E)-stained slides were retrieved and reviewed by a team of soft-tissue pathologists at the Royal National Orthopaedic Hospital, London, UK. Immunohistochemistry and fluorescent in situ hybridisation studies were performed on cases without definitive diagnosis on routine H and E. Results: Fifty-two cases were studied. The male-to-female ratio was 1:1.3, with a median age of 33 years. Most sarcomas (57.5%) were of intermediate malignant potential according to 2013 World Health Organization classification. Kaposi sarcoma (37.5%), undifferentiated sarcomas (22.5%), dermatofibrosarcoma protuberans (15%) and myxofibrosarcomas (7.5%) were the most common sarcomas seen in adults. There was no case of liposarcoma. Sarcomas in the younger age group (<20 years) accounted for 23.1% of cases with embryonal rhabdomyosarcoma accounting for the majority. Conclusion: Soft-tissue sarcomas in adults in Lagos Nigeria show a different morphologic spectrum than those reported in Western countries.
Keywords: Histopathological, Lagos, Nigeria, sarcomas, soft-tissue
|How to cite this article:|
Ikeri NZ, Akinjo AO, Ajayi OO, Fehintola Banjo AA. Histological types of soft-tissue sarcomas at the lagos university teaching hospital. Niger Postgrad Med J 2017;24:205-9
|How to cite this URL:|
Ikeri NZ, Akinjo AO, Ajayi OO, Fehintola Banjo AA. Histological types of soft-tissue sarcomas at the lagos university teaching hospital. Niger Postgrad Med J [serial online] 2017 [cited 2018 Feb 20];24:205-9. Available from: http://www.npmj.org/text.asp?2017/24/4/205/223464
| Introduction|| |
Liposarcomas are among the most common soft-tissue sarcomas reported in the literature. They account for 17.6% of soft-tissue sarcomas in the US, 15% of all sarcomas in France (including visceral sarcomas) and 13% of all sarcomas in the UK.,, However, general pathologists in Nigeria rarely come across such diagnoses in their daily practice. On the other hand, kaposi sarcoma (KS), which accounts for only 0.9% of soft-tissue sarcomas in Western literature, appears to be fairly common in Nigeria, certainly more common than liposarcomas. Indeed, most practicing general pathologists will come across such cases in their day-to-day routine. This suggests a difference in the histological spectrum of soft-tissue sarcomas in the Nigerian population when compared to reports from the Western societies. A diligent search, however, for data on the common soft-tissue sarcomas in our environment revealed no comprehensive data. Factors responsible for this include the rarity of soft-tissue sarcomas compared to other malignancies, the low number of specialist soft-tissue pathologists, a limited number of available ancillary immunohistochemical and molecular testing which is often required for making diagnosis, and the unaffordability of such tests where available.
A knowledge of the histological spectrum of soft-tissue sarcomas is important for the establishment of an effective sarcoma service as it allows for the planning of treatment strategies at multidisciplinary team meetings. The determination of appropriate panels, probes or primers for ancillary immunohistochemical and molecular testing, the development of protocols for running such ancillary tests, the development of protocols for optimal fixation and handling of the tissue specimen, and a baseline on which further research can be performed are other benefits of knowing the histologic spectrum of sarcomas. Overall, knowledge of the histopathologic spectrum of soft tissue sarcomas will help improve the quality of pathology and overall clinical service offered in an institution. The aim of this study, therefore, was to determine the histologic spectrum of soft-tissue sarcomas received in our institution over a period of 5 years.
| Materials and Methods|| |
Archival haematoxylin and eosin (H and E)-stained slides containing formalin-fixed paraffin-embedded tissue sections of cases of soft-tissue sarcomas diagnosed at the Department of Anatomic and Molecular Pathology, Lagos University Teaching Hospital, Nigeria from January 2012 to December 2016 were retrieved and reviewed with the team of specialist soft-tissue pathologists at the Royal National Orthopaedic Hospital, London, UK. Where definitive diagnosis could not be reached on H and E, immunohistochemistry and fluorescence in situ hybridisation were performed.
Immunohistochemistry was performed on representative blocks using the Leica Bond 3 fully automated immunohistochemistry staining system. The choice of panels used for each individual case depended on the morphology of the tumour and the differential diagnoses entertained. These included SMA, S100, desmin, myogenin, caldesmon, MNF116, EMA, CD45, TdT, MUC4, STAT6, HMB45, vimentin, INI1, CD99, CD31, CD117 and synaptophysin. Appropriate positive controls were used for each of the individual stains.
Fluorescence in situ hybridisation (FISH) was performed using probes for MDM2 (Abbott Molecular, USA), EWSR1 (Abbott Molecular, USA), TFE3 (Zytovision, Germany) and SS18 (Abbott Molecular, USA) for cases suspected to be well-differentiated liposarcoma, Ewing sarcoma, alveolar soft part sarcoma (ASPS) and synovial sarcoma, respectively. For these cases, deparaffnised sections were pretreated with deionised water in a pressure cooker for 5 min and digested with pepsin at 37°C for 50 min. Subsequently, the tissue sections and appropriate FISH probes as listed above were codenatured at 72°C for 10 min and hybridised overnight at 45°C, after which washing was performed. Slides were then counterstained with 4, 6-diamidino-2-phenylindole and mounted with coverslips. At least 50 non-overlapping nuclei were assessed for the relevant cytogenetic changes using a fluorescence microscope (Olympus BX61, Japan) that was equipped with appropriate filters, a charge-coupled device camera (Olympus XM10), and the FISH imaging and capturing software Cell Imaging system (Olympus Soft Imaging Solution, Germany). The data obtained was classified and analysed using the Statistical Package for the Social Sciences for Windows version 22.0 (IBM, Armonk, NY, USA), and represented in tables, charts and graphs. Ethical approval was obtained from the institutional Health and Research Ethical Committee.
| Results|| |
In all, 64 cases were reviewed, 12 of which were found to be either benign, inadequate for diagnoses, carcinomas or lymphomas. These were excluded from further study. Of the remaining 52 cases, 12 (23.1%) occurred in the patients <20 years, while 40 (76.9%) were seen in adults. The mean age of occurrence was 35.5 years, median age was 33 years, peak age was in the 30s, and the age range was 3 months to 79 years. [Figure 1] shows the age distribution of all cases of soft tissue sarcomas. There was a slight female predominance in all age groups with an overall male-to-female ratio of 1:1.3. The male-to-female ratio was 1:1.4 in paediatric cases and 1:1.2 in adults.
The most common sarcomas seen overall were KS (30.8%), the unclassified/undifferentiated sarcomas (23.1%) and dermatofibrosarcoma protuberans (DFSP) (13.5%) [Table 1]. All but one case (93%) of KS was associated with HIV infection. Most paediatric sarcomas had round cell morphology with embryonal rhabdomyosarcoma accounting for the majority of cases (41.7%). In adults, most cases (55%) were of intermediate malignancy according to the 2013 World Health Organization classification of soft tissue tumours. These included KS (37.5%), DFSP (15%), and solitary fibrous tumour (2.5%). Among the high-grade sarcomas undifferentiated pleomorphic sarcoma (12.5%), pleomorphic leiomyosarcoma (7.5%) and grade 3 myxofibrosarcoma (7.5%) were the predominant tumours seen. No case of liposarcoma was seen. Representative photomicrographs are shown in [Figure 2].
|Figure 2: Photomicrographs of representative lesions. (a and b) Photomicrograph of solitary fibrous tumour showing spindle cells with immunopositivity for STAT6 arranged around prominent vascular network. (c and d) Botryoid rhabdomyosarcoma with cambium layer (arrow) and immunopositivity for desmin. (e) Kaposi sarcoma showing proliferative slit like spaces, erythrocyte extravasation and prominent spindle cell component. (f) Extraskeletal osteosarcoma showing malignant cells within a fibroadipose tissue depositing osteiod|
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|Table 1: Histologic distribution of childhood and adult soft tissue sarcomas|
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FISH was performed on 4 cases, 1 suspected to be ASPS, Ewing sarcoma, well-differentiated liposarcoma and synovial sarcoma. None of the characteristic genetic rearrangements, however, were seen. Most soft-tissue sarcomas (with the exclusion of KS which occurred in multiple sites) occurred in the lower limbs (36.1%) with the head/neck (22.2%) and trunk (22.2%) following. [Table 2] shows the distribution of the tumours by their location.
|Table 2: Distribution of soft tissue sarcomas by location (excluding kaposi sarcoma)|
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| Discussion|| |
Like the major cancers seen in our environment, soft-tissue sarcomas occur much earlier than in Western societies. Mean age of occurrence of cancers from two cancer registries in Nigeria were reported as 49.1 and 45.4 years which is much earlier than a median age of 66 years reported in the US., This is especially true for breast and colorectal cancer, with mean ages of 44.8 and 46 years compared to 62 and 67 years in the US.,, The mean age of soft tissue sarcomas in this study was 35.5 years, with a peak age of occurrence in the 30s. This is also lower than reports from the UK (peak age >65 years) and the US (median age 60 years)., In a study conducted in southern India, the peak age of occurrence was the 30–60 age group. At first glance, one might think that this is due to the peak age of occurrence of KS (the predominant sarcoma in this study) being in the 30s. However, when KS is excluded, the mean age drops from 35.5 to 32 years. This suggests that even in the absence of HIV infection, soft-tissue sarcomas would still occur three decades earlier in Lagos than in Western societies. Comparing this figure with a mean age of soft tissue sarcomas in African–Americans (mean age 53 years), we infer that environmental factors are the most plausible cause for the earlier incidence of soft-tissue sarcomas in Lagos, Nigeria.
KS was the most common sarcoma seen in this study. It accounted for 38% of cases, which is high compared to 0.9% in the US, 8.9% in a multicentre study of cases in France and Italy and 4.7% in the UK.,, All but one case (93%) was due to HIV infection. It is pertinent to note that most KS cases (63.2%) diagnosed in our institution were not subject to histopathological assessment. This means that the incidence of KS is much higher than is reported in this study. The much higher rate of HIV infection in sub-Saharan Africa than in Western societies explains the higher incidence of KS. In one report in India, there was no case of KS diagnosed in the 5-year period of the study.
Most soft-tissue sarcomas in Western populations are designated sarcoma not otherwise specified, i.e., cases where the specific morphogenic subtype was not reported for various reasons. In this study they accounted for 23.1% of cases and were second only to KS. These cases showed no evidence of differentiation towards a specific lineage after being subjected to an exhaustive immunohistochemical panel. One of these cases had the growth pattern reminiscent of ASPS, however deletion of the TFE gene was seen on FISH instead of the translocation that defines ASPS.
Of cases with known morphotypes, leiomyosarcomas and liposarcomas are the most common sarcomas in most reports. Liposarcoma is more common subtype in the US (17.6%), India (18%) and some European regions (23.9%), while leiomyosarcoma is more common type in the UK (18.5%).,, No case of liposarcoma was seen during the 5-year period of this study. This is a significant finding though the reason for this is unknown, which is not surprising since the general predisposing factors for liposarcomas are largely unknown. Leiomyosarcomas were also fairly uncommon in this study (6.0%). Two of the three cases occurred in the jaw of females which is in contrast to the retroperitoneum, the most common location reported in the literature. The round cell sarcomas featured more prominently in children in this study, with embryonal rhabdomyosarcoma occurring as the predominant childhood sarcoma (41.7%). Most of these occurred in the head (40%), and this is consistent with reports worldwide.
The limbs are the most common site of occurrence of soft tissue sarcomas. In the UK they account for 25% of all sarcomas including visceral sarcomas. In Europe, they account for 49% of soft-tissue sarcomas and 31.9% of all sarcomas including those in visceral sites. In our study, the limbs also were the most common site of occurrence after KS was excluded (because of its propensity for multiple sites on the skin) accounting for 55.6% of all cases. More cases were seen in the lower limbs (36.1%) than the upper limbs (19.4%).
Based on the above findings, the establishment of an effective sarcoma service necessitates that immunohistochemical panels for HHV8, factor XIII, desmin, myogenin, SMA, caldesmon are particularly important. S100, EMA, MNF116, CD45, CD99 will also be useful to diagnose the less common lesions, as well as mimics of sarcomas such as carcinomas, lymphomas and melanomas. Probes for EWSR and SS18 should also be considered considering the significant proportion of undifferentiated round cell sarcomas seen in the study. Multidisciplinary team meetings are essential for proper clinicopathological correlation and treatment planning.
| Conclusion|| |
There are significant epidemiological and morphological differences between soft-tissue sarcomas in Lagos and those reported in Western literature. They occur three decades earlier in our environment. Liposarcomas and leiomyosarcomas which are the most common adult soft-tissue sarcomas in the Western population are rare in our environment with HIV-associated KS accounting for the majority. Similarities, however, shared by both populations include the limbs as the most common tumour site and embryonal rhabdomyosarcoma being the most common childhood soft-tissue sarcoma. HHV8, factor XIII, desmin, myogenin, SMA and caldesmon are particularly important for the establishment of an effective sarcoma service in Lagos.
Team of soft tissue Pathologists at the Royal National Orthopaedic Hospital, London UK.
Financial support and sponsorship
The project was sponsored by Union for International Cancer Control.
Conflicts of interest
There are no conflicts of interest.
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