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Rising Trend of Adenocarcinoma of Cervix: A Global Perspective


Rising Trend of Adenocarcinoma of Cervix: A Global Perspective

*Akhter S,1 Khatun S2

 Abstract

Worldwide incidence of invasive cervical cancer including squamous cell carcinoma has been decreasing for the last 40 years, but incidence of adenocarcinoma of cervix shows a steady increase. This increase is mostly reported from the developed countries with organised cancer screening system and cancer registries. Human papillomavirus (HPV) has been established as the most important etiological factor for cervical cancers including adenocarcinoma. This review article discussed the epidemiological data from several articles including meta-analyses and international projects to give an overview of the increasing incidence of cervical adenocarcinoma throughout the world. The article then delved into the epidemiological studies that provided data regarding association of HPV with adenocarcinoma of cervix. It is evident from these studies that HPV types 16, 18 and 45 are responsible for more than 90% of adenocarcinoma of cervix. Differences in type specific HPV prevalence among countries might be the reason for the variation in the incidences of adenocarcinoma of cervix from region to region. The rising trend in the incidence of cervical adenocarcinoma can be explained as a cohort effect related to increased exposure to prevalent HPV infection in younger women, and also to less effective performance of cytology screening methods in detecting glandular lesions of cervix. In this context, the currently available prophylactic vaccines against HPV should come in the frontier to prevent occurrences of invasive cervical cancer including adenocarcinoma worldwide.

[Journal of Histopathology and Cytopathology, 2018 Jan; 2 (1):56-62]

 Key words: Cervical cancer, Adenocarcinoma, Incidence, Human papillomavirus

 

  1. *Dr. Shabnam Akhter, Associate Professor of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka. akhtershabnam66@gmail.com
  2. Shahana Khatun, Assistant Professor of Pathology, MH Samorita Hospital and Medical College, Dhaka

*For correspondence

 

Introduction

Worldwide incidence of invasive cervical cancer has been decreasing over the last 40 years owing to organised as well as opportunistic practices of cytology screening mostly in the developed countries.  Majority of cervical cancers are squamous cell carcinomas (SCC), while adenocarcinomas (ADC) are small in number. There is no doubt that cytology screening programs have lead to increased detection and early management of precursor lesions of cervical carcinoma. However, despite the decline in overall incidence of cervical cancer, several studies have reported increasing incidence of cervical ADC in comparison to SCC, particularly among younger women and mostly in the developed countries since the 1970’s.1-6

When German virologist Harold zur Hausen and his team, after their extensive works from 1972 to 1984, revealed their revolutionary discovery that human papillomavirus (HPV), notably HPV 16 and HPV 18, are causative agents of cervical cancer, subsequent researches related to cervical cancer were directed towards HPV. Several years later, Bosch et al. (1995)7 reported from their international survey that 93% of cervical cancers contained HPV DNA. They also found that the prevalence of HPV did not show variation between histologic subtypes of cervical cancer (SCC, ADC and adenosquamous carcinomas). By 1999, Walboomers et al.8 published their seminal studyfindings that the prevalence of HPV in cervical cancers was 99.7% worldwide, thus proclaiming that infection with high-risk HPV was central to the pathogenesis of almost all cervical cancers.

With this background this review article will give an overview of the changing trend of cervical ADC from the data provided by epidemiological studies. The studies are mostly from the developed countries of North America and Europe, while few international works have also included data from underdeveloped countries of Asia, Africa and South America.3,9 In the latter half of the article, the etiological aspect of cervical ADC will be discussed, that will include the role of HPV and other risk factors identified so far.

 Rising trend of adenocarcinoma of cervix

Peters et al.1 reported in 1986 about increase in the proportional incidence of ADC of the cervix during 1972-1982 among white women aged less than 35 years in Los Angeles County, California. The authors’ thought that this was due to use of oral contraceptives before the age of 20 years. Being intrigued by such observation, Schwartz and Weiss2 followed the rates of invasive cervical cancer by age, time period and histologic types between 1973 and 1982 among 8,647 women identified by the SEER (The Surveillance, Epidemiology, and End Results) program registries. They found that the incidence of ADC of the cervix in women under the age of 35 years had increased more than twofold between 1973 and 1982. They speculated that other potential risk factors related to sexual behaviour were also to be considered, as for example, in young women early age at first intercourse or increased number of sexual partners concurred with the early use of oral contraceptives.

Vizcaino et al. (1998)3 conducted a study with International Agency for Research on Cancer (IARC) to find out the time trends in the incidence of cervical ADC, particularly in young women. They collected incidence data on ADC and adenosquamous cell carcinoma during the period 1973-1991 from 60 population-based cancer registries of 32 defined populations in 25 countries. Their analyses focused three aspects of the incidence trend: age, calendar period of diagnosis and birth cohort. The final results reported a significant increase in incidence among women born after 1930 in the United States (white and Hispanic women), Canada, Australia, United Kingdom, Denmark, Sweden, Slovakia and Slovenia. Increasing trend was also observed in Bombay (Mumbai, India), in Japan (Osaka) and among Chinese women in Singapore. The analyses also showed that besides age, the increasing incidence was found related to year of birth, with each successive cohort showing higher risk at a given age compared with their precedent cohorts. However, a decreasing trend was also observed in Finland, France and Italy, and no significant changes in incidence were found in several other countries. The authors concluded that part of the increase might be due to an increasing prevalence of HPV infection and partly to increased detection of atypical glandular lesions by cytology screening.3

Later, Smith et al. (2000)4 used the SEER (The Surveillance, Epidemiology, and End Results) database to identify all cases of cervical cancer registered from 1973 to 1996 with the objective to find out the trends in the age-adjusted incidence of ADC of the uterine cervix relative to SCC in the United States. Their results showed that over 24 years the age-adjusted incidence rates decreased for all invasive cervical cancers by 36.9% and for SCC by 41.9%, but increased for ADC by 29.1%. The percentage of SCC relative to all cervical cancer had decreased from 76.21% (between 1973 and 1977) to 70.17% (between 1993 and 1996). On the other hand, percentage of ADC had increased from 12.4% (1973-1977) to 24.2% (1993-1996). The findings were all in favour of the fact that the absolute frequency as well as the relative frequency of ADC showing a rising trend.4

Subsequently Bray et al. (2005)5 carried out a study to examine the secular trends in the incidence of ADC of cervix in women ages <75 in 13 European countries using an age-period-cohort- model. The study reported that age-adjusted ADC incidence rates had increased throughout Europe, the rate of increase ranging from around 0.5% per year in Denmark, Sweden, and Switzerland to ≤3% in Finland, Slovakia and Slovenia. The increases were calculated first to affect generations born in the early 1930s through the mid-1940s, with risk rising in women born in the mid-1960s relative to those born 20 years earlier.5

Bulk et al. (2005)6 of Netherlands did a population-based study on the incidence of invasive cervical cancer to evaluate trends in relation to age at time of diagnosis. The cases were collected from the Netherlands Cancer Registry for all women with invasive cervical cancer between 1989 and 1998. The results depicted that in this 10-year period, the incidence of SCC had decreased substantially from 7.1/100,000 to 6.1/100,000, and the incidence of ADC overall remained static, but it had increased in women aged 15-29 and in women aged 30-44.6

 Etiological factors related to adenocarcinoma of cervix

ADC of cervix, like SCC, has been reported to be associated with high-risk HPV infection, which is considered to play the central role in cervical carcinogenesis.7-9 So, the etiological factors will be discussed in two parts, the first will be about the association of HPV in ADC of cervix, and the second part will encounter the postulated risk factors other than HPV infection.

 HPV and adenocarcinoma of cervix

With regard to increasing incidence of cervical ADC, Andersson et al. (2000)10 tried to find out the presence of HPV in diagnosed cases of ADC of cervix during 1986-1996, the cases identified through Swedish Cancer Registry. HPV was identified in 71% cases of ADC; in the HPV-positive cases, HPV18 was present in 52% and HPV16 in 33%. They also reported that the prevalence of HPV in ADC differed with age; women <40 years were HPV-positive in 89% of cases, while women ≥60 years were HPV-positive in 43% cases.

Clifford et al. (2003)11 carried out a meta-analysis and reported HPV18 to be the most frequent type (37.7%) in ADC followed by HPV 16 (31.3%) and HPV 45 (5-7%), whereas HPV 16 was the dominant type in SCC of cervix. On the other hand, the population-based study by An et al. (2005)12 in Korea revealed that HPV16 was the most frequent type followed by HPV 18, while overall HPV prevalence in the cervical ADC among Korean women was 90%.

To find out the extent to which HPV and cofactors may be responsible for the increasing trend of cervical ADC, Castellsague et al. (2006)13 examined eight case-control studies during 1985-1997 from eight different countries with differences in the incidence of cervical cancer. Countries were from North Africa, South America and Southeast Asia. They found HPV to be the main risk factor, prevalence ranging from 86% in Paraguay to 100% in Algeria. HPV16 and HPV18 were the most dominant HPV types, together being present in 82% of the cases.

International Collaboration of Epidemiological Studies of Cervical Cancer (2006)14 conducted a collaborative reanalysis from 12 epidemiological studies. Their analyses revealed that HPV16 was the commonest type in both SCC and ADC of cervix. However, HPV16 was more common in SCC (56% versus 40%) whereas HPV18 was more common in ADC (35% versus 16%). Similarly, Smith et al. (2007)15 published their meta-analysis update on HPV type distribution covering six continents where they reported that HPV positivity overall was a little more in SCC (90%) than in ADC (85%), HPV16 was less frequent in ADC (33%) and more frequent in SCC (55%), and HPV18 was the dominant type in ADC (37%) compared with SCC (13%). They also found that HPV 16/18 proportion was higher in Europe, North America and Ocenia (74-77%) than in Africa, Asia and South/Central America (65-70%).

On behalf of the Retrospective International Survey and HPV Time Trends Study Group, Silvia de Sanjose (2010)16 completed an international project with the aim to provide distribution pattern of HPV genotypes in samples of invasive cervical cancer. Samples were collected covering 38 countries from Europe (10), North America (USA), central South America (10), Africa, Australia and Asia (12 including Bangladesh). From the analyses of data, they found that HPV types 16, 18 and 45 were the three most common types in each histological type of SCC, ADC and adenosquamous cell carcinoma of cervix. Both HPV18 and HPV45 were more common in ADC than in SCC. The other intriguing finding was that cancers related to HPV18 and HPV45 occurred at a much younger age (<50 years). The early presentation of invasive cancers in these cases indicates that these virus types possibly require a short time of progression to invasive cancer with a high integration rate into the host genome.

Afterwards, Pirog et al. (2014)17 did a worldwide analysis of HPV prevalence and genotypes in different histological subtypes of cervical ADC. They found that relatively narrow spectrum of high-risk HPV types, HPVs 16, 18 and 45 were present in the vast majority of ADC, together constituting 94.1% of HPV-positive cases. In contrast to the earlier meta-analyses by Clifford et al. (2003)11 and Smith et al. (2007)15, they found HPV16 to be the most frequent type (50.9%) followed by HPV18 (31.6%) and HPV 45 (11.6%) in HPV-positive ADC cases. Though the ratio of HPV16 to HPV18 in ADC varied from study to study, the percentage of combined HPV16 and HPV18-positive cases were found much uniform among studies (75.7-94.8% of cases) with an average of 89.8%.

To find out the HPV subtypes in cervical ADC in women of Bangladesh, Akhter et al. (unpublished data, presented as poster at the Annual meeting of USCAP 2017)18 studied 71 cases of cervical ADC. The results showed that, in contrast to western countries, HPV16 was the most frequent type (63.4%) followed by HPV18 in 16.9%. HPV DNA was detected in 100% cases. These data indicate a significant epidemiological difference in the type-specific prevalence of HPV between the developed and underdeveloped countries.

 Risk factors other than HPV infection

The other risk factors for ADC are more or less similar to those for cervical cancer in general, being related to factors that promote spread of HPV infection from person to person as any other sexually transmitted disease.

Several studies12,14,19-21 have worked with risk factors associated with cervical ADC in comparison to SCC. The notable risk factors other than HPV are described in the following sections.

  1. Lifetime number of sexual partners was reported to show strong association with both SCC and ADC, risk of cancer increasing with the increasing number of partners.12,14,19-21
  2. Earlier age at first intercourse was found to be associated with increased risk of both SCC and ADC of cervix, the association being stronger for SCC.12,14,19-21
  3. Longer duration of use of oral contraceptives was reported to be strongly related to risk for both SCC and ADC.12,14,19-22
  4. Smoking was considered a risk factor for SCC compared to never smokers whereas it was found not to be a risk for adenocarcinoma. 12,14,19-21
  5. High parity showed significant association with both SCC and ADC (three or more live births or full-time pregnancies versus none), the association being stronger for SCC. 12,14,19-21
  6. Herpes simplex virus type 2 (HSV-2) seropositivity was reported to be associated with a more than twofold increase in the risk of cervical ADC.12

 Conclusions

The review discussions have highlighted infection with high-risk HPV as the most important etiological factor for cervical ADC. In terms of type specific prevalence, HPVs 16, 18 and 45 are reported to be responsible for more than 90% of ADC of cervix. Differences in type specific HPV prevalence among countries may be responsible for the variation in the incidences of ADC of cervix from region to region. The rising trend in the incidence of cervical ADC can be explained as a cohort effect related to increased exposure to prevalent HPV infection in younger women, and also to less effective performance of cytology screening methods in detecting glandular lesions of cervix. In this context, the currently available prophylactic vaccines against HPV should come in the frontier to prevent occurrences of invasive cervical cancer including adenocarcinoma of cervix worldwide.

 References

  1. Peters RK, Chao A, Mack TM, et al. Increased frequency of adenocarcinoma of the uterine cervix in young women in Los Angeles County. JNCI 1986; 76:423-8.
  2. Schwartz SM and Weiss NS. Increased incidence of adenocarcinoma of the cervix in young women in the United States. American Journal of Epidemiology 1986;124(6): 1045-47.
  3. Vizcaino AP, Moreno V, Bosch FX, Munoz N, Barros-Dios XM and Parkin DM. IARC. International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas. International Journal of Cancer 1998; 75: 536-545.
  4. Smith HO,Tiffany MF, Qualls CR and Key CR. The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States – A 24-year population-based study. Gynecologic Oncology 2000; 78: 97-105.
  5. Bray F, Carstensen B, Moller H, Zappa M, Zakelj MP, Lawrence G et. al. Incidence trends of adenocarcinoma of the cervix in 13 European countries. Cancer Epidemiol Biomarkers Prev 2005; 14(9): 2191-99.
  6. Bulk S, Visser O, Rozendaal L, Verheijen RH, Meijer CJ. Cervical cancer in the Netherlands 1989-1998: decrease of squamous cell carcinoma in older women, increase of adenocarcinoma in younger women. Int J Cancer 2005; 113:1005-1009
  7. Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. JNCI 1995;87(11):796-802
  8. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189(1): 12-19.
  9. Parkin DM and Bray F. Chapter 2: The burden of HPV-related cancers. Vaccine 2006. Doi: 10.1016/j.vaccine.2006.05.111
  10. Andersson S, Rylander E, Larsson B, Strand A, Silfversvard C, Wilander E. The role of human papillomavirus in cervical adenocarcinoma carcinogenesis. European Journal of Cancer 2001;37:246-250.
  11. Clifford GM, Smith JS, Plummer M, Munoz N and Franceschi S. Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer 2003; 88: 63-73.
  12. Castellsague X, Diaz M, Sanjose S, Munoz N, Herrero R, Franceschi S et al. Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: Implications for screening and prevention. Journal of the National Cancer Institute 2006; 98(5): 303-315
  13. An HJ, Kim KR, Kim IS, Kim DW, Park MH, Park IA et al. Prevalence of human papillomavirus DNA in various histological subtypes of cervical adenocarcinoma: a population-based study. Modern Pathol 2005;18:528-534.
  14. International Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: Collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int. J. Cancer 2006;120:885-891.
  15. Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis update. Int. J. Cancer 2007;121:621-632.
  16. Silvia de Sanjose, Quint WGV, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B et al. on behalf of the Retrospective International Survey and HPV Time Trends Study Group. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol 2010; 11:1048-56.
  17. Pirog EC, Lloveras B, Molijin A, Tous S, Guimera N, Alejo M et al. HPV prevalence and genotypes in different histological subtypes of cervical adenocarcinoma, a worldwide analysis of 760 cases. Modern Pathol 2014; 27: 1559-67.
  18. Akhter S, Kamal M, Barua AR, Sung CJ, Lawrence WD, Quddus MR. Adenocarcinoma of cervix is surging: Is high-risk HPV subtype(s) infection pattern changing in a cervical carcinoma prevalent developing country? A retrospective PCR-based study. Poster presentation at the Annual Meeting of USCAP 2017. San Antonio, Texas, USA
  19. Green J, Berrington de Gonzalez A, Sweetland S, Beral V, Chilvers C, Crossley B et al. Risk factors for adenocarcinoma and squamous cell carcinoma of the cervix in women aged 20-44 years: the UK National case-control study of cervical cancer. Br J Cancer 2003;89:2078-2086.
  20. Berrington de Gonzalez A, Seetland S and Green J. Comparison of risk factors for squamous cell and adenocarcinomas of the cervix: a meta-analysis. Br J Cancer 2004;90:1787-1791.
  21. Altekruse SF, Lacey JV, Brinton LA, Gravitt PE, Silverberg SG et al. Comparison of human papillomavirus genotypes, sexual, and reproductive risk factors of cervical adenocarcinoma and squamous cell carcinoma: Northeastern United States. Am J Obstet Gynecol 2003;188:657-63.
  22. Lacey JV Jr, Brinton LA, Abbas FM, Barnes WA, Gravitt PE, Greenberg MD et al. Oral contraceptives as risk factors for cervical adenocarcinomas and squamous cell carcinomas. Cancer Epidemiol Biomarkers Prev 1999;8:1079-85.

 

 

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Cytological Findings of Testicular Fine Needle Aspiration of Azoospermic Men


Cytological Findings of Testicular Fine Needle Aspiration of Azoospermic Men

 *Alam MA,1 Islam MS,2 Hossain N3

 The technique of fine needle aspiration (FNA) has a role as a reliable, quick and easy method of obtaining testicular cells. Recent advances in the management of male infertility or sub fertility and in particular, the finding that spermatozoa recovered from epididymis and testis can result in embryo generation after intracytoplasmic sperm injection (ICSI), question the traditional role of open testicular biopsy for the assessment of spermatogenesis. The purpose of this article was to find out the role of testicular fine needle aspiration cytology in male infertility and to provide brief information on method of needle aspiration, interpretation of testicular fine needle aspiration cytology for evaluation of spermatogenesis, its advantages, limitations and complications as compared to testicular biopsy. Adequate sample were obtained from 62 (84.93%) cases, while 11 (15.06%) cases had inadequate smears where cytological examination could not be possible. The adequate smears were categorized as maturation arrest in 25 (40.32%) cases, sertoli cell only in 21(33.87%) cases, normal spermatogenesis in 10 (16.12%) cases and hypospermatogesis in 6 (9.67%) cases. Testicular FNAC is a significant laboratory technique for the investigation of selected cases of male infertility. Compared to open biopsy, FNA has a number of advantages. Infertile male with severe spermatogenesis disorders can give birth to their own children, whereas only a few years ago the same group of men had only to choose between sperm donation and adoption.

[Journal of Histopathology and Cytopathology, 2018 Jan; 2 (1):51-55]

Key words: Cytology, Fine needle aspiration, testis, azoospermia

  1. *Dr. Md. Ashraful Alam, Associate Professor, Department of Pathology, Rangpur Medical College. drashraful09@gmail.com
  2. Md. Shahidul Islam, Associate Professor, Department of Urology, Rangpur Medical College, Rangpur.
  3. Nusrat Hossain, Junior Consultant, Gynaecology and Obestritics.Palashbari Health Complex, Gaibandha.

 *For correspondence

Introduction

Fine needle aspiration cytology (FNAC) of superficial as well as of deep seated lesions today is a well recognized diagnostic procedure for the diagnosis of neoplastic as well as non-neoplastic and inflammatory lesions. Recently, it has gained popularity for its diagnostic and therapeutic role in male infertility. Since times immemorial the wife has always been blamed for infertility especially in third world countries. Failure to find sperms in post coital test, conducted by Max Huhner in 1913, raised the possibility that husband could be responsible for infertility or sub-fertility. Approximately, 20% cases of infertility are caused entirely by male factor with additional approximately, 30% to 50% of infertile couples.1,2 Azoospermia or absent sperm in semen occurs in approximately, 5% to 10% of infertile men who are evaluated.2 Azoospermia may be obstructive azoospermia (OA) or non-obstructive azoospermia (NOA). The obstructive may have no significant effect on spermatogenesis and may be amenable to surgery, whereas, before introduction of intracytoplasmic sperm injection (ICSI), the only available option for men with NOA was adoption or sperm donor. Assessment of spermatogenesis is an important component in the diagnostic algorithm of male infertility. Traditionally, the testis biopsy has been the gold standard in this evaluation because it provides information in cases of both suspected obstruction and in failing on obstructed testes. Any technique to assess spermatogenesis must be minimally invasive and must conserve as much testicular tissue as possible. It should  not only provide qualitative but also quantitative information about spermatogenesis. In addition to answering the question whether sperm production is normal, it must also address whether sperms are present at all within the testis, as with advances in field of reproductive medicine, even a single sperm can now give men with NOA chance to enjoy biological fatherhood.3 FNAC of the testis is a simple, quick, minimally invasive and painless procedure. The sample can be obtained in outpatient department, can be more representative than biopsy as several separate punctures can be made in one sitting, and there is no local severe pain, haematoma or scarring.

The purpose of this study was to find out the role of testicular fine needle aspiration cytology in male infertility and to provide brief information on method of needle aspiration, interpretation of testicular fine needle aspiration cytology for evaluation of spermatogenesis, its advantages, limitations and complications as compared to testicular biopsy.

Methods

This is an observational study. Fine needle aspiration was performed in 73 azoospermic persons from January 2016 to June 2017 in a private diagnostic laboratory of Rangpur city, Bangladesh. Detailed history and physical examination was performed on all azoospermic people. In addition, semen analysis report was evaluated to confirm azoospermia. Hormonal evaluation including testosterone and FSH levels were obtained in the majority of cases.

FNA Technique

Testicular FNA was done under local anesthesia. The scrotal skin was cleaned by spirit and cotton and bilateral spermatic cord block was achieved by giving 5 to 7 ml of 2%  lignocaine. To quicken the distribution of anesthetic, spermatic cord was gently massaged after injection. After several minutes the testis was firmly palpated to ensure absence of pain. Then the testis was positioned with epididymis and vas deferens directed posteriorly, safe from injury. The scrotal skin was stretched taut over the testes by wrapping the scrotal skin behind the testes with a sponge. Testes was aspirated at three different sites, upper, middle and lower part, using 23 G needle with 10  ml disposable syringe attached to it. Precise gentle in and out movement, varying from 5-8 mm were used. After aspiration, the persons were advised for rest for at least ten minutes. Aspiration was done from both testes for evaluation of spermatogenesis. Slides were prepared from the aspirated material and fixed in 95% alcohol and stained with Papanicolaou (Pap) stain.

Contraindication for bilateral testicular sampling included the presence of local skin infection, hydrocele, orchialgia or previous biopsy.

 FNA Interpretation

All stained FNA cytological smear was interpreted for:

  1. The presence or absence of mature spermatozoa with tails.
  2. Specimen adequacy, as previously reported, an adequate, and informative, FNA specimen was defined as one that contained at least 100 clusters of 20 or more cells or at least 2000 well-dispersed testicular cells.4

 Results

FNA was performed in 73 cases of azoospermic men. The mean age of these men was 32.5 years with a range from 22 to 50 years with period of infertility more than one year. The testicular aspirates were adequate for opinion in 62 cases (Table I) out of 73 cases. The cytological diagnoses in aspirate from 73 cases are depicted in (Table II).

Table I: Adequacy of testicular smears

 

Type of sample No of smears %
Adequate 62 84.93%
Inadequate 11 15.06%

Adequate smears were categorized on cytological examination into Table II:

  1. Normal spermatogenesis in 10 (16.12%) cases.
  2. Sertoli cell only in 21 (33.87%) cases.
  3. Hypo spermatogenesis in 6 (9.67%) cases.
  4. Maturation arrest in 25(40.32%) cases.

Normal spermatogenesis of testes on FNA revealed all germ cell maturation steps from spearmatogonia till mature spermatozoa.

Maturation arrest category shows no spermatozoa, with presence of immature germ cells, including primary spermatocytes and spermatids.

Sertoli cells only on FNA of testes showing only sertoli cell.

Spermatogonia were seen as large cells with round nuclei and finely granular chromatin with a thin rim of cytoplasm 5

During our study 2 (2.73%) person complained severe pain. No one complained prolong pain or any haematoma formation.

Table II: Cytological diagnosis of 73 cases

 

Cytological diagnosis No. of cases (%)
Normal spermatogenesis 10(16.12%)
Sertoli cell only 21(33.87%)
Hypo spermatogenesis 6(9.67%)
Maturation arrest 25(40.32%)

 

 

 

 

 

 

Figure 1. Photomicrograph showing sertoli cell only (x400)

 

 

 

 

 

 

Figure 2. Photomicrograph showing hypo- spermatogenesis (x400)

Discussion

Posner and Huhner first used testicular puncture biopsies in the investigation of human infertility that examined unstained samples for spermatozoa.6  Later fine needle aspiration of the testis pioneered by Obrant and Persson (1965) was proposed as a non invasive technique.6 Characterizing the cell types was straightforward, with not much difficulty in recognizing germ cells and sertoli cells were adequate. The materials aspirated by FNAC were adequate in majority of cases (84.93%). The adequacy rate has similarity with the findings of  Ahmed.7 In our study, normal spermatogenesis was found by testicular FNAC in 16.12% of cases of azoosperic men. This finding, however, differed from the findings observed in a study done by Kuerin A et al.8 This may be  due to small number of cases in our study. In our study maturation arrest and sertoli cell only found in 40.32% and 33.87% cases respectively which were similar to the findings found by Ahmed. In our study we found 9.67% cases of hypospermatogenesis which are similar to the findings of Ahamad SU et al9 and RC Adhikari findings.10

In the present study we have done multiple aspirations of both testes under local anaesthetia by cord blocking. Some author performed aspiration by giving per rectal diclofenac sodium suppository.

Most of the authors have performed FNA under general anaesthetia or local anaesthetia. Verma A K et al performed FNA without general or local anaesthetia and found the technique is well tolerated by the most patients.11  Single aspirate may not be truly representative.12 However some studies have described sampling in one testis.10,13 The study used sampling of both testes and findings were also different in both testes. Adhikari RC observed severe pain after FNA procedure in 31.68% cases and haematoma in 2.97% person. Which was completely different observation from our observation. Rajawanshi et al.14,15 observed only complication was prolonged pain in some patients. In our study we noted only 2.73% persons complained prolong pain but no haematoma formation, that are similar observation with Ahamad MSU et al.

 Conclusion

Testicular FNAC is a significant laboratory technique for the investigation of selected cases of male infertility. Compared to open biopsy, FNA has a number of advantages;  therefore, it is already used as a diagnostic and therapeutic method in some andrology centers. FNA combined with the introduction of ICSI (intracytoplasmic sperm injection) have revolutionized the management of male infertility in the  recent years. Infertile male with severe spermatogenesis disorders can have their own children, whereas only a few years ago the same group of men had only to choose between sperm donation and adoption.

References

  1. Sigman M, Jarow JP. Male infertility. In:Walsh PC, Retik AB, Vaughan ED, Weij AJ, Kavoussi LR, Norvick AC, et al,editors. Campbell’s urology. 8th ed. Philadelphia, WB Saunders, 2003: p.1476.
  2. Jarow JP, Espeland MA, Lipshultz LI.Evaluation of the azoospermic patients. J Urol, 1989;142:62-5.
  3. Balselv E, Francis D, Jacobsen GK. Testicular germ cell tumors, Classification based on fine needle aspiration biopsy. Acta cytol, 1990; 34:690-94.
  4. Turek PJ, Cha I, Ljung BM. Systematic fine needle aspiration of testis: correlation to biopsy and results of organ ”mapping” for mature sperm in azoospermic men. Urology, 1997; 49:743-8.
  5. Tauchmanova L, Alviggi C,Foresta C, Srtina I, Gaolla A, Colao A, et al. Cytzoospermia with normal testicular function after allogenic stem cell transplantation: a case report. Hum Reprod 2007; 22:495-9.
  6. Persson PS, Ahren C,Orbant KO. Aspiration biopsy smear of testis in azoospermia cytology versus histological examination.Scand J Urol Nephrol, 1971; 5:22.
  7. Basim Sh. A. Cytological findings of testicular fine needle aspiration in a sample of azoospermic Iraqi patients. Mustansiriya Med Journal, 2012; V11 (2):24-28.
  8. Kurien A, Mammen K,Jacob S. Role of fine needle aspiration cytology (FNAC) of testes in male infertility.Indian J Urol, 2003;19:140-4.
  9. Ahamad MSU,Islam SMJ, Chowdhury, Khanam SA,Ahmed ASMM. Teasticular FNAC in Azoospermia. Chattagram Maa-O Shishu Medical College Journal, 2014;13(1):46-8.
  10. Adhikari R C. Testicular fine needle aspiration cytology in azoospermic males. Nepal Med Col J, 2009; 11(2):88-91.
  11. Verma AK, Basu D,Jayaram G. Testicular cytology in azoospermia. Diagn Cytopathol 1993; 9:37- 42.
  12. Skakkeback NE, Hammen R, Philip H, Rebbe H. Quantitation of human seminiferous epithelium.Histological studies in 44 infertile men and controls with normal chromosomal complements. Acta Pathol Microbiol scand 1973; 81:97-111.
  13. Mahajan AD, Ali NI,Walwalker SJ, Rege JD, Pathak HR. The role of fine needle aspiration cytology of the testis in the diagnostic evaluation of infertility. Brit J Urol Intl, 1999; 84:485-8.
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Skin Tumours Diagnosed at Department of Pathology, Sir Salimullah Medical College, Dhaka During Two Years Study Period


Skin Tumours Diagnosed at Department of  Pathology, Sir Salimullah Medical College, Dhaka During Two Years Study Period

*Hossain MD,1 Islam MN,2  Kabir E ,3  Begum S 4

Abstract

During the past century, cancer has emerged as the most challenging problems for public health systems in medium and low income countries. With a cancer load of more than one million, Bangladesh is not an exception. In this study we found that  squamous cell carcinoma was the most common malignant tumour and lipoma was the most common benign tumour of skin adnexa. The lower income generating group was the more vulnerable group for both benign and malignant tumours. It also showed that both benign and malignant tumours were more common in patients with risk behaviours as well as in patients with no risk behaviours. Tumours of the skin adnexa were the most common benign tumour found in our study

[Journal of Histopathology and Cytopathology, 2018 Jan; 2 (1):47-50]

 Key words: Skin, Tumour

  1. *Dr. Md. Delwar Hossain, Lecturer, Department of Pathology, Sir Salimullah Medical College, Dhaka. mehruddelwar@gmail.com
  2. Professor Dr. Md. Nasimul Islam, Professor and Head, Department of Pathology, Sir Salimullah Medical College, Dhaka
  3. Professor Dr. Enamul Kabir, Professor, Department of Pathology, Sir Salimullah Medical College, Dhaka
  4. Shahnaj Begum, Assistant Professor, Department of Pathology, Sir Salimullah Medical College, Dhaka

 

*For correspondence

Introduction

Cancer burden causes serious health problems both in developed and developing countries.1 Cancer has devastating effect on individual, family and society of Bangladesh. Cancer is one of the major causes of morbidity and mortality among the non-communicable diseases in our population. Appropriate prevention of cancer deserves urgent attention since the disease is expected to double in the next 20 to 25 years in most of the  countries.1 Cancer in Bangladesh is one of the major killer diseases like many other countries particularly because of ubiquitous exposure to environmental carcinogens, oncogenic viruses and microorganisms, coupled with lack of screening, awareness and poor health seeking behaviors associated with poverty, malnutrition and illiteracy. The magnitude of the problem from cancer is often unrecognized by health and general policy makers alike to other  overwhelming and more visible competitive   health problems and natural calamities.

According to Bangladesh Bureau of Statistics cancer is the sixth leading cause of death in Bangladesh.2 The number of people developing cancer is expected to increase in number mainly because of increase in life expectancy and life style factors. Each year more than 200,000 people develop cancer and 150,000 die of the disease. International Agency for Research on Cancer (IARC) has estimated death from cancer in Bangladesh was 7.5 % in 2005 and will be increased up to 13 %  in 2030.3  

IARC has projected death from 10 leading cancers in females of Bangladesh (2002) are: (1) mouth and oropharyngeal, (2) cervical, (3) breast, (4) oesophageal, (5) ovarian, (6) Lung, (7) lymphoma, (8) stomach, (9) liver and (10) colorectal cancer.3

IARC has projected death from 10 leading cancers in males of Bangladesh (2002) are: (1) mouth and oropharyngeal, (2) lung, (3) oesophagus, (4) lymphoma, (5) stomach, (6) bladder, (7) liver, (8) leukaemia, (9) colorectal and (10) prostate cancer.3

During the 2 years study period 2908 histopathological cases and 5187 cytopathological cases were diagnosed at the department of Pathology and 70 haematological malignant tumours were handled at the department of Haematology, Sir Salimullah Medical College (SSMC) and Mitford Hospital, Dhaka.4 This study was done to find out patterns of skin tumours in these cases.

Methods

This study was partial presentation of a two years tumour registry study done at the Department of Pathology, SSMC, Dhaka from 1 July, 2013 to 30 June, 2015. It was a cross-sectional observational study done on all patients diagnosed as cases of both benign and malignant tumors by cytopathology, histopathology and haematology.

 Data collection procedure

A predesigned questionnaire both in Bangla and English was developed according to MacLennan method and software was generated with the technical assistance by the University of Chicago Research Bangladesh by the cooperation of department of Pathology, Bangabandhu Seikh Mujib Medical University (BSMMU), Dhaka. Prior to the commencement of this study, approval was taken from the Ethical Review Committee of SSMC. Each patient was interviewed and relevant information was recorded systematically in a prescribed format. A written consent also attached with the questionnaire and was explained before the patient/patient’s guardian. The first part of the questionnaire was designed to record the demographic details of patients. The second part of the questionnaire was to record the pathological diagnosis of tumour with its ICD 0-3 and ICD-10 codes.  The information collected was entered into the database by software Microsoft Access 2003 and Visual Basic 6.

Recording of Data

The data were recorded according to database software. All the patients were supplied 1st part of the questionnaire (topography portion) during access to the department for submission of the specimen or for FNAC or other procedures. The data were entered case after case from the filled up questionnaire received from the patients during collection of their reports following a self-made registrar which recorded 10 items for each case likely  (1) case serial number, (2) specimen type –histopathological, cytopathological or haematological specimen (3) referred by, (4) yearly serial number i.e., accession number (5) diagnosis, (6) sites of specimen, (7) date of diagnosis and (8) Reported by.

Data were entered into the computer database software accordingly.

 Analysis of the data

Statistical analyses of the results were obtained by using Microsoft access and Window based computer software devised with Statistical Packages for Social Sciences (SPSS-15). The information was partially coded according to ICD-10 (International Classification of Diseases version-10) and ICD-3 (International Classification of Diseases – Oncology version 3).

 Results

Out of total 767 benign tumours of skin and skin adnexa lipoma was found in highest number in 91.13%, ganglioneuroma in 4.05%, nevus in 0.92%, benign fibrous histiocytoma in 0.65% and all were found more in female patients than males in both age group. On the other hand neurofibroma in 1.69% and benign mesenchymal lesion in 0.65% found more in male than female patients in both age groups (Table I)

Out of 49 malignant tumours of skin squamous cell carcinoma was found in highest number in 55.10% and 99.63% in male patients and none in female of adult age group but found only in one female of paediatric age group which was the only malignant tumour of skin of this age group. Basal cell carcinoma 22.45% and malignant melanoma 6.12% were found more in female than male and deratofibrosarcoma 10.21% and verrucous carcinoma 6.12% were found more in male than female  patients only in adult age group  (Table II).

Table I: Diagnostic distribution of benign tumours of skin / skin adnexa according to age and sex

 

Diagnosis Paediatric Adult Total (%)
Male Female Male Female
Lipoma 15 29 302 353 699 91.13
Neurilemoma/Ganglioneuroma 2 4 12 13 31 4.05
Neurofibroma 5 1 5 2 13 1.69
Nevus 0 1 1 5 7 0.92
Epithelioid mesothelioma benign 1 0 3 1 5 0.65
Benign fibrous histiocytoma 1 0 1 3 5 0.65
Fibromatosis 1 0 0 1 2 0.26
Squamous papilloma 1 0 1 0 2 0.26
Pilomatricoma 0 0 1 1 2 0.26
Cylindroma 0 0 0 1 1 0.13
Total 26 35 326 380 767 100.00

 

Table II: Diagnostic distribution of malignant tumours of skin according to age and sex:

 

Diagnosis Paediatric Adult Total (%)
Male Female Male Female
Squamous cell carcinoma 0 1 26 0 27 55.10
Basal cell carcinoma 0 0 5 6 11 22.45
Dermatofibrosarcoma 0 0 4 1 5 10.21
Verrucous carcinoma 0 0 2 1 3 6.12
Malignant melanoma 0 0 1 2 3 6.12
Total 0 1 38 10 49 100.00

 Discussion

A total of 767 benign and 49 malignant tumours of skin and skin adnexa those were diagnosed in this study found more in females than males both in paediatric and adult age group patients. Highest benign tumour of skin and skin adnexa found in this study was lipoma followed by ganglioneuroma, neurofibroma, nevus, benign mesenchymal lesion, benign fibrous histiocytoma, fibromatosis, sqamous papilloma, pilomatricoma and cylindroma. Squamous cell carcinoma was the highest malignant tumour of skin found in this study only in adult males but in no females of adult age group. Squamous cell carcinoma was found only in one female child of the paediatric age group. No other malignant tumour was found in paediatric age group either in male or female. The next malignant tumour of skin was basal cell carcinoma which was found more in adult females than in adult males. Both dermatofibrosarcoma and verrucous carcinoma were found more in male than in female. The NICRH also showed that about 60% of the male cancer patients were smokers and among them more than half (53%) had squamous cell carcinoma.5 Farhad et al. also found lipoma was the top one (35.70%) benign tumour of skin adnexa.6 Lipoma, ganglioneuroma and nevus in both age group were found more in female than in male. Neurofibroma and benign mesenchymal lesion found in both age groups were more in male than in female.

 Most of the patients were from low income generating groups and they were house wives, students, unemployed, garments or industrial workers and hawkers. The patients were mainly illiterate and a few number of the study patients were mostly up to SSC level educated. Most of the study patients were Muslim and a small number were Hindu. Most of the patients hailed from Dhaka city followed by Munshigonj, Shariatpur, Madaripur, Comilla, Manikgonj, Narayangonj, Bhola, Kishoregonj, Patuakhali, Gazipur and Narsingdi and also from other districts of Bangladesh. Out of total 64 districts of Bangladesh patients from only 7 districts were unavailable.

Conclusion

Cancer registries play a major role in providing the data to justify the establishment, implementation and monitoring of a national cancer control programme, therefore, stability in cancer registration is of pivotal importance.

This is the partial study of the two years study done (from July 1st, 2013 to June 30th, 2015) on “Establishment of Pathology Based Tumour Registry at SSMC, Dhaka.” The whole study like this one along with other institutions of the country may pave the path of a nationwide population based cancer registry in future.

 

References

  1. Iqbal S. Cancer: A Bangladesh perspective

(http://ds.cc.yamaguchi-u.ac.jp/~applied/initiative/18-internship-houkokusyo/kiseitai/Iqbal-Mohd.Shamim.htm)

  1. Bangladesh Bureau of Statistics, 2008: Faiz et al, 2008.
  2. Wagner G (1991). History of cancer registration. In Jensen OM, Parkin DM, MacLennan R, Muir CS, and R.G. Skeet RG, editors. Cancer Registration: Principles and Methods. IARC Scientific Publications No. 95. Lyon, France. IARC.2002. p.22-28.
  3. Delwar et al. Establishment of Pathology Based Tumour Registry at Sir Salimullah Medical College, Dhaka, Bangladesh. December, 2015. P. 19 (Thesis).
  4. National Institute of Cancer Research and Hospital (NICRH), Dhaka December, 2009. Zaman MM and BakiMO (eds) (2009). 2005-2007:1-19.
  5. Farhad et al. Pathology Based Tumour Registry at BSMMU Shahbagh, Dhaka. 2013. p.57.