Small cell carcinoma of cervix: Rare andenigmaticSameer A. H' Ansari, Arvind G. Valand, Ralshree D. Katkel, Aradhana B. Deka, Vishakha C. JadhavDepartments of Pathology and Grant Government Medical college and Sir J.J. Hospital, lDepartment ol obstetrics and Gynecotogy, cama and AlblessHospital, Mumbai, Maharashtra, lndia

ABSTRACT

Small cell carcinorna ofthe cervix is a rare, poorly differentiated neuroendocrine tumor ofcervix showing a high propensity to spr€adto l1'rnph nodes as well as distant metastasis. Earlier considered to be a rariant of squamous cell carcinoma, it i, no* acknowledgea

it-Il,],Ii:i i,r,*o*,lp *lrkers of neuroendocrine differentiation. Because of the dismal prognosis, it is important to make eirlydiagnosis and to diffbrentiate it from a small cell variant of squamous cell carcinoma and other differenrials. We present a case of a45.year.oIdfemaIewhopresentedwithcervicalgrowth'

, Key,words; Cervixr metastasis, neu...ra..rine; small rell

I NTRO DUCTIO N

Small cell carcinoma (SmCC) is a tumor of neuroendocrineorigin commonly seen in the lung. ExtrapulmonarySmCC accounts for 5% of the total incidence.tu Withina female genital tract, the cervix is one of the rare sitesfor this tumor. Other sites of SmCC include vulva andvagina.lSl SmCC of cervix accounts for approximately 2yoof all invasive cervical malignanry.Ei Most of the studieshave shown a dose association of SmCC cervix with humanpapillomavirus (HPV) infection.lkl

CASE REPORT

was uneverrfful. Her general and systemico<aminations wereunremarkable. On per vagrnal examination, a huge, friablegrowth was present in the cervix extending into right andIeft parametrial tissue. Ultrasonography abdomm revealed awell-defined hypoechoic mass of size 10.5 crn x 9.7 crn x 9.4 onseqn arising from the cervix resulting in obstruction ofendometrial cavity causing pyometra. The fat planes betweenthe lesion of urinary bladder appeared to be maintained.However, fat planes between the anal canal and the masscannot be commented upon. Positron emission tomographyscan showed metabolically active soft-tissue mass in cervixalong with bilateral extemal and intemal iliac lymph nodesand precaval and aortocaval lymph nodes present. Cervicalbiopsy was performed. On gross examinatiory multiplefragmented tissue bits totally aggregating to 1cc, grayishwhite were received. Histopathological examination revealeda tumor arranged in sheets and nests in a background ofderse inflammatory infiltrate [Figure 1]. The individual hrmorcells showed salt and pepper duomatin with incorspicuousnudeoli pigure 2]. Immunohistodremistry revealed leukorytecouunon antigen (LCA) negativity along with positivity forsynaptophysin [Figure 3] favoring the diag:nosis of SmCCof the cervix. HPV testing was negative ruling out theassociation of this tumor with it. The patienthad underwent aradical hysterectomy and bilateral pelvic lymphadenectomy.Postoperative phase of the patient was unevenfful. She wasgiven three cydes of chemotherapy. She is followed up andis still under treaknent.

A 4S-year-old perimenopausal female, para 7, Live 7 birthcomes with complain of urinary reterrtionsince 15 days. patient

was catheterized for the same in a private hospital. patimt alsohad foul smelling per vaginal disdrarge since 15 days alongwith excessive bleeding since 2 montfu. Her merskual history

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Address for correspondence: Dr' Sameer Abdul Hamid Ansari, Grant Medical college and sir J.J, Hospilal, Mumbai - 400 00g, Maharashtra, India,E-mail: drsameeransari @ yahoo.co.in

Ansari, el al: Small cell carcinoma ceruix

Flgura l: Pholomicrograph showing an itlilirative small round cell lumourarranged in diffuse sheets admixed with inflammatory cells (H and E, x40)

Figure 2: High power view showing tumor cells with salt and pepper chromatinand inconspicuous nucleoli with a foci of necrosis (H and E, ,200)

Figure 3: lmmunohistochemisiry showing synaptophysin positivity (lHC, x400)

DISCUSSION

Small cell carcinoma arises from the neuroendocrine cellslocated within the normal epithelium throughout thefemale genital tract. In the earlier days, it was considered

to be rare, highly aggressive subtype of squamouscell carcinoma. However, later evidences proved thatmost of these tumors express one or more markers ofneuroendocrine differentiation.lS.$ Hence, now labeled as

a separate entity. SmCC of the cervix have been related toHPV infection. Studies have demonstrated the presenceof HPV virus type 18 DNA or messenger RNA in themajority of SmCC cases.lJ.cll Our patient, however, did notshow infection by HPV. The mean age of presentation,as mentioned in the literature is around fourth to fifthdecade.l?l Our patient was also in the same age group.The common clinical presentations include abnormalvaginal bleeding and obvious mass in most cases.llZl Ourpatient also had similar complaints. Grossly the tumorsare usually ulcerative and infiltrative making the cervixbarrel shaped.l9l On histopathology, SmCC is composedof small blue cells with high nuclear - rytoplasmic ratio,scant cytoplasm, and markedly hyperchromatic nucleiwith speckled chromatin. Nuclear molding is present andnucleoli are inconspicuous. It showed increased mitoticactivity (>10 mitoses/l0 HPF). Furthermore, the tumorshows areas of necrosis and apoptosis.l?l The tumor patternmay vary from sheet-like, insular or perivascular andthick trabeculae with serpiginous growth architecture.t8lOn immunohistochemistry, the tumor shows positivityfor at least one neuroendocrine marker (synaptophysin,chromogranin, CD56) and shows negativity for LCA.laaaat

Our case reveal same findings, thus confirming thediagnosis. Electron microscope shows dense core granulesin most cases along with tightly packed cells with closeapposition of cell membranes.l?I The differential diagnosison histopathology includes poorly differentiated SmCC, orpoorly differentiated adenobarcinoma or small cell variantof SmCC, non-Hodgkin's lymphoma.l&!21 Furthermore,SmCC often develops in concomitance with usual SmCCor adenocarcinoma, hence it becomes very important todo immunohistodremistry.Pl It is extremely drallenging toestablish the diagnosis of this tumor on a small cervicalbiopsy because of its limited paraffin tissue and by thefact that it can show fragmentatiory crush artifacts andstreaming effects. The rare occurrence of SmCC of thecervix had made it difficult to define precise treatmentguidelines for the management of this tumor.lzl Radicalhysterectomy with bilateral lymphadmectomy, radiationtherapy, and chemotherapy are the treatrnent modalitiesfor this tumor with the special role of dremotherapy.ttl gssof adjuvant dremotherapy or d:remoradiation is associatedwith better survival in such patients.tl9l Since it has a highpropensity to metastasis, it is mandatory to do full bodycomputed tomography scan and magnetic resonanceimaging along with bone marrow examination in allpatients to know the stage of the tumor.l3l McCusker ef al.had concluded in his studies that the survival was worsewith this tumor with short disease-free period and earlyrecurrences.l9}

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Ansari, el al: Small cell carcinoma cervix

To conclude, SmCC is a rare, poor differentiatedneuroendocrine tumor having high propensity to nodaland distant metastasis with dismal prognosis and need earlydiagnosis with prompt search for metastasis to increase thesurvival rates of the patient.

REFERENCES

Nouni K, Chenna H, Berhil H, Iraqi M, Kebdani T, Hassouni K,et nl. Small cell carcinoma of the cervix: Report of four casesand literah:re revierv. Open access scientific reports 2012;1:394.Doi:1 0.4172lscientilicreports.394.

Iiljgue""-v.qkl1ni9-N,I-tiy-gE-Bero*9,"8:ig"ndrt:L9J""ep-!,.}p.flm-1ll SelI ne.uro-eld-qgjle cqr{no-:rLa ofllre Sg.ryix:.A r-are en!i!y-.

I. 91i]t' D_i"agrr_Bes 201 ft 9: 132-8.

4$ip9S \,IJ,.FSrgt -C_D.,-s]1ell cSll-SSrci.t-1g$+ gr !ls*1llS:*1S.S"ersil

in a pr-egnanlpe[e-nt di4gnq:94 with liqqid b_ased cytolggy"?nd-ceIlblock immulo.gLt-g-*emistry, 91se Rep Patl:gl *2014;2014:97.*gl?sl,p:alL!}*.5!z]1427"!!*,.Efilgo*S.Metge!9_YP,"FpFp4.oli4ej, Piqggll& Iruebalo-L_De *osa .N, e-r- nJ-9Irall cgl]. $euroel9-o-cJir}e cervigal*c-alc-ilema

wilF J;y.e.elJoUory:Upt q.,*s"g..le"p*qrL ell rg"v_iely. ,1,nlir*nc_qr B,erz$g;?2#7-:.V,

4nhlgs"B4. Parl 19, il'ah KV (srnsn BJ. Eys"Lltetlq! o-{

hi'lslp"El9-r[9ph9ll19tl1""*erq"]mm"g19lrrs_!94e]li_el q.*s.rg*lsSsd{si"!!iql*4iqgry_ql...q{q:,Lqll.sgl!_sxl*oi*9:tsltsssryirvi!b-p-?llcubl-r9fsr$:s_te.-hs!-n-qr}--p-epiUgrrllygt$ .!yff!-lg atd19..M-egI-+1h_.-1"1?.s-1.LQgq-*?_a,we1g1Q.UgJtLXS"lrHCJg]llu-BR Sm"all cqll calqir-roma. otlhe.*\ltenrrs-ce-*3lt*.prefi n4{rsy:A-calg.r"-e-pgTtand.rgyiel:'_9f Ji}E[ler.i*sp. ptqe] !e.qq ?q 1 I ;9.2 1 -eiDolFol S, Tai Y, thgo Y,.Ji3lg J, 5"o-lF B. AJetro:pectivecli*is-opathg"lg8ical grr-ralysis gf small-cs*ll cq*ir.roma of. $g uterinecervlx. Mol Clin-O4col 2014;2:71-7_9.

Eichhorn jH, Young RH. Neuroendocrine tumors of theBenital tract pathology and patterns review. Am J Clin Pathol2007;775:94-112.N4'*c"g*"t !IP, So!( I"R., Cleqff .li{, Ier:qq.'"pli-ry'H*4o.'Hs.tg![9'qqf ths u tq !i4e. ggrvix : -IISld en c-e",.. {emo g r a p hi c"s*Snd su *r"-iyela1U.-!911p4Ifq9I- to -tqgsggl+.p-..9ell c-q3-lgro.1511. gyne_col..Oncol

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-c"aJ_9inom?,"9f Jhe qgryl}rTleatmqrrj pl-rd suryivalol+Jcgmes-911-9q p glignte. 4q] L -olqlet

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Cite this article as: Ansari SA, Valand AG, Katke RD, Deka AB,Jadhav VC. Small cell carcinoma ol cervix: Bare and enigmatic. ClinCancer lnvestig J 2015:4:548-50.

Source ot Support: Nil, Conllict of lnterest: None declared_

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