An audit of local experience, histological classification of primary tumours of the thyroid according to WHO revised criteria with a critical account

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An audit of local experience, histological classification of primary tumours of the thyroid according to WHO revised criteria with a critical account
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  endocrine tumours and found reactivity correlatedstrongly with the WHO grading system. 7 The current study has demonstrated that the vastmajority of endocrine tumours encountered at differentsites in the tubular gastrointestinal tract express CK19irrespective of differentiation, size, lymphovascularinvasion, Ki67 index, necrosis, mitotic count or depthof invasion of the bowel wall. Five of the seven poorlydifferentiated rectal cases showed only 10–30% of thetumour cells to be CK19+. CK19, therefore, does notidentify more invasive and  ⁄    or aggressive behaviour of endocrine tumours of the gastrointestinal tract and,unlike in the pancreas, does not appear to have a rolein the immunohistochemical evaluation of gastrointes-tinal and appendiceal endocrine tumours. Runjan ChettyStefano SerraRicha JainMark Evans 1 Kumarasen Cooper 1 Anita Iyer 1 Department of Pathology, University HealthNetwork  ⁄    University of Toronto, University of Toronto, Ontario, Canada and, 1 Department of Pathology, Vermont College of Medicine, Burlington, VT, USA 1. Cheung CC, Ezzat S, Freeman JL, Rosen IB, Asa SL. Immunohis-tochemical diagnosis of papillary thyroid carcinoma.  Mod. Pathol. 2001;  14;  338–342.2. Uenishi T, Kubo S, Yamamoto T  et al.  Cytokeratin 19 expressionin hepatocellular carcinoma predicts early postoperative recur-rence.  Cancer Sci.  2003;  94;  851–857.3. Bhatavdekar JM, Patel DD, Chikhlikar PR  et al.  Molecularmarkers are predictors of recurrence and survival in patientswith Dukes B and Dukes C colorectal adenocarcinoma.  Dis. ColonRectum  2001;  44;  523–533.4. Deshpande V, Fernandez-del Castillo C, Muzikansky A  et al. Cytokeratin 19 is a powerful predictor of survival in pancreaticendocrine tumors.  Am. J. Surg. Pathol.  2004;  28;  1145–1153.5. Ali A, Serra S, Asa SL, Chetty R. The diagnostic utility of CK19and CD99 in pancreatic endocrine tumors.  Am. J. Surg. Pathol. 2006;  30;  1588–1594.6. La Rosa S, Rigoli E, Uccella S, Novario R, Capella C. Prognosticand biological significance of cytokeratin 19 in pancreaticendocrine tumours.  Histopathology  2007;  50;  597–601.7. Schmitt AM, Anlauf M, Rousson V  et al.  WHO 2004 criteria andCK19 are reliable prognostic markers in pancreatic endocrinetumors.  Am. J. Surg. Pathol.  2007;  31;  1677–1682.8. Solcia E, Kloppel G, Sobin LH.  Histological typing of endocrinetumours . New York: Springer, 2000.9. Rindi G, Kloppel G, Ahlman H  et al.  TNM staging of foregut(neuro)endocrine tumors: a consensus proposal including agrading system.  Virchows Arch.  2006;  449;  395–401.10. Rindi G, Kloppel G, Couvelard A  et al.  TNM staging of midgut andhindgut (neuro)endocrine tumors: a consensus proposal includ-ing a grading system.  Virchows Arch.  2007;  451;  757–762. An audit of local experience, histologicalclassification of primary tumours of thethyroid according to WHO revised criteriawith a critical account  DOI: 10.1111/j.1365-2559.2009.03338.x Sir:  Thyroid nodules (TN) are a common clinicalproblem in Pakistan as in the rest of the world. Theyare more common in women and in areas of iodinedeficiency. Exposure to ionizing radiation in childhoodand adolescence increases the risk of both nodules andthyroid carcinoma. Most TNs are benign hyperplasticlesions, but 5–20% are true neoplasms. 1–3 Solitary thyroid nodules (STN) may represent amultitude of thyroid disorders, and thorough knowl-edge of the epidemiology of thyroid diseases is of paramount importance. Medical history and physicalexamination of the patient adds significantly to thedetermination of the nature of the TN. A STN has ahigher incidence of malignancy. Their incidence, how-ever, is significantly higher in endemic goitrousregions, in females and with increasing age. 4,5 Many thyroid diseases can manifest clinically as aSTN. The differential diagnosis of a STN can be broadlyclassified into benign and malignant. Solitary nodulesof the thyroid that are encapsulated can be classified asadenoma, carcinoma, or a follicular variant of papillarycarcinoma. Its peculiar nuclear features define afollicular variant of papillary carcinoma, which allowsfor its diagnosis in both cytological and histologicalpreparations. The diagnostic distinction between follic-ular adenoma (FA) and carcinoma (FC) necessitates theexamination and interpretation of well-prepared histo-logical sections. 6,7 During a 5-year period from 1 July 1999 to 30 June 2004, thyroid tissue samples submitted to theDepartment of Pathology, King Edward Medical Uni-versity, Lahore, from four major Surgical Units of Mayo Hospital were histologically classified. WorldHealth Organization (WHO) criteria were the goldstandard for histological classification of all samples.Relevant thyroid scans and laboratory investigationsof the patients assisted in the histological classificationof lesions.Out of a total of 1628 thyroid surgical specimens,427 (26.3%) were shown to comprise neoplasticlesions and 1201 (73.3%) non-neoplastic lesions. All   2009 The Authors. Journal compilation    2009 Blackwell Publishing Ltd,  Histopathology ,  55,  114–132. 120  Correspondence  lesions were more common in women compared withmen, giving a male:female ratio of 1:3.5. As regardsneoplastic lesions, 320 cases (75%) were benignadenomas (Figure 1) and 107 (25%) were malignant.Most of the adenomas were the follicular variant. Inthe malignant category, papillary carcinoma (PC)was the commonest (71%) while the second mostfrequent malignancy was FC (13%). Others consistedof anaplastic carcinoma (APC) (8.4%) and med-ullary carcinoma (MC) (3.7%). There were 307  ⁄   320 (94.7%) typical follicular adenomas, whereas13  ⁄    320 (4.1%) were oncocytic (Hu¨rthle cell variant),2  ⁄    320 (0.6%) were clear cell variants and 2  ⁄    320(0.6%) were atypical adenoma. On review of thehistological features of all PCs, 65  ⁄    76 (85.5%) wereclassical PC, 6  ⁄    76 (7.9%) were of follicular variants,while 1  ⁄    76 (1.3%), 1  ⁄    76 (1.3%) and 1  ⁄    76 (1.3%)were capsulated PC, diffuse sclerosing variant and tallcolumnar variants, respectively. Ground glass appear-ance, pale staining and nuclear overlapping were foundin 100 cases of PC, whereas vascular core, nuclearinclusions, grooving, pseudoinclusion, irregularity innuclear outlining, large size of nuclei, psammomabodies, presence of follicles, presence of stromal fibro-sis and squamous metaplasia were found in 70  ⁄   76 (92.2%), 62  ⁄    76 (81.5%), 59  ⁄    76 (77.6%), 55  ⁄    76(72.3%), 52  ⁄    76 (68.5%), 48  ⁄    76 (63%), 45% (59.2%),31  ⁄    76 (40.8%), 6  ⁄    76 (8%) and 4  ⁄    76 (5.2%), respec-tively (Table 1). Three cases of FC were widely invasive,among them a young woman aged 23 years withdistance metastasis, whereas all the others were of minimally invasive type. There were 6  ⁄    14 (42.85%)minimally invasive FC, 7  ⁄    14 (50%) widely invasiveFC, and 1  ⁄    14 oxyphilic (Hu¨rthle cell) variant of  A CDB Figure 1. A , Photomicrograph (H&E) of follicular adenoma (arrow) showing no invasion of capsule.  B , Photomicrograph of minimally invasivefollicular carcinoma showing capsular invasion (arrow).  C , Photomicrograph (H&E) showing papillary structures lined by overlapping epithelialcells that have cleared nuclei. Psammoma bodies are also visible (arrow).  D , Photomicrograph (left side) showing medullary carcinoma of thyroid, calcification (long arrow) and amyloid deposition (long arrow) seen on a background of neoplastic cells (double arrows).   2009 The Authors. Journal compilation    2009 Blackwell Publishing Ltd,  Histopathology ,  55,  114–132. Correspondence  121         T      a        b        l      e       1  .     H    i   s    t   o     l   o   g    i   c   a     l   c     l   a   s   s    i     fi   c   a    t    i   o   n   o     f   p   a   p    i     l     l   a   r   y   c   a   r   c    i   n   o   m   a   s   o     f    t     h   e    t     h   y   r   o    i     d     (    7    6        ⁄     1    0    7   ;    7    1     %     )    H    i   s    t   o     l   o   g    i   c   a     l   v   a   r    i   a   n    t   s    N   u   c     l   e   a   r     f   e   a    t   u   r   e   s    V   a   s   c   u     l   a   r   c   o   r   e    P   s   a   m   m   o   m   a     b   o     d    i   e   s    F    i     b   r   o   u   s   s    t   r   o   m   a    S   q .    M   e    t    M   u     l    t    i    F   o     l   c    G   r    G   g    P   s    I    N    L   s    I    O    P   s    I    C   y    t .    I   n    O   v   e   r     l   a   p   p    i   n   g    T   y   p    i   c   a     l    P    C    6    5        ⁄     7    6     (    8    5 .    5     %     )    5    2    6    5    6    5    5    6    4    3    3    4    5    3    2    3    6    5    6    5    4    1    5    4    2    3    F   o     l     l    i   c   u     l   a   r   v   a   r    i   a   n    t    6        ⁄     7    6     (    7 .    9     %     )    3    5    6    2    4    1    1    1    6    0    2    0    0    5    M    i   c   r   o    P    C    2        ⁄     7    6     (    2 .    6     %     )    1    2    0    2    0    0    0    0    2    2    0    0    0    2    C   a   p   s   u     l   a    t   e     d    P    C    1        ⁄     7    6     (    1 .    3     %     )    1    1    1    1    1    1    1    1    1    1    1    0    0    1    D    i     f     f   u   s   e   s   c     l   e   r   o   s    i   n   g    1        ⁄     7    6     (    1 .    3     %     )    1    1    1    0    0    0    0    0    1    1    1    1    0    0    O    t     h   e   r   s    1        ⁄     7    6     (    1 .    3     %     )    1    1    1    1    0    0    0    0    1    1    0    0    0    0    T   o    t   a     l    5    9     (    7    7 .    6     %     )    7    6     (    1    0    0     %     )    7    6     (    1    0    0     %     )    6    2     (    8    1 .    5     %     )    4    8     (    6    3     %     )    5    2     (    6    8 .    5     %     )    5    5     (    7    2 .    3     %     )    2    5     (    3    2 .    9     %     )    7    6     (    1    0    0     %     )    7    0     (    9    2 .    2     %     )    4    5     (    5    9 .    2     %     )    6 (    8     %     )    4 (    5 .    2     %     )    3    1     (    4    0 .    8     %     )    P    C ,   p   a   p    i     l     l   a   r   y   c   a   r   c    i   n   o   m   a   ;    G   r ,   g   r   o   o   v   e   ;    G   g ,   g   r   o   u   n     d   g     l   a   s   s   a   p   p   e   a   r   a   n   c   e   ;    P   s ,   p   a     l   e   s    t   a    i   n    i   n   g   ;    I    N ,    i   n   c   o   n   s   p    i   c   o   u   s   n   u   c     l   e   o     l    i   ;    L   s ,     l   a   r   g   e   s    i   z   e   ;    I    O ,    i   r   r   e   g   u     l   a   r   o   u    t     l    i   n   e   ;    P   s    I ,   p   s   e   u     d   o    i   n   v   a   s    i   o   n   ;    C   y    t .    I   n ,   c   y    t   o   p     l   a   s   m    i   c    i   n   v   a   g    i   n   a    t    i   o   n   ;    S   q .    M   e    t ,   s   q   u   a   m   o   u   s   m   e    t   a   p     l   a   s    i   a   ;    M   u     l    t    i    F   o     l   c ,   p   r   e   s   e   n   c   e   o     f     f   o     l     l    i   c     l   e   s .   2009 The Authors. Journal compilation    2009 Blackwell Publishing Ltd,  Histopathology ,  55,  114–132. 122  Correspondence  FC. Capsular invasion was seen in 100% cases of FC,whereas the other histological features were variable.One case of MC was a young man, associated withmultiple endocrine neoplasia type 2 syndrome, whilethree cases were diagnosed as primary thyroid cancer.All MCs had a polygonal, spindle cell mixed populationof cells. One of the MCs showed a small cell populationas well. Amyloid and calcitonin was detected in allcases of MC. Seven cases (7  ⁄    107; 6.5%) were of APCshowing a varying population of polygonal cells, giantcells, spindle cells and sarcomatoid morphology. Therewas high degree of mitosis and pleomorphism with lossof differentiation to any particular variant of thyroidcarcinoma. There were 2  ⁄    107 (1.8%) cases of poorlydifferentiated thyroid carcinoma (PDTC) with somehistological features indicating FC with brisk mitosis,insular pattern and necrosis. There were two cases of non-Hodgkin’s lymphoma and two cases of non-thyroid srcin carcinoma due to local extension fromsurrounding malignancy.In our study, benign tumours (follicular adenomas)constituted 75% and malignant tumours 25%, giving aratio of benign to malignant of 3:1. In the study byHussain  et al. 8 , the incidence of malignancy was14.35%, whereas Deveci  et al. 9 found malignancy in22% of cases. 8,9 In our study the female:male ratio was 3.5:1.According to Deveci  et al. , 9 the predominance of women in thyroid tumours is in accordance with theworld-wide experience that all thyroid lesions arepredominantly disorders of women. The age range of thyroid tumours (both benign and malignant) in ourstudy was 18–80 years (mean 46 years). In our studymost of the cancer cases were seen at >30 years,consistent with other studies; however, this age isdecreasing compared with previous studies in Pakistanand world-wide. There were 302  ⁄    320 (94.7%) typicalFA and 13  ⁄    320 (41%) oxyphilic adenoma. We alsodiagnosed two cases of clear cell adenoma and twocases of atypical adenoma on the basis of WHOcriteria, but experienced problems in subclassifyinginto microfollicular and macrofollicular adenoma dueto non-availability of suitable criteria. We usedsubjective criteria and compared the size with histo-logically normal follicles. In our study, capsulation hasbeen accepted as one of the important histologicalfeatures, whereas compression was not found in alladenomas, although the morphological and architec-tural features were also found in all lesions. Thesefeatures are in accordance with the study conductedby Qureshi  et al. , 10 but they did not follow WHOcriteria and gave the frequencies separately as FA(97%) and Hu¨rthle cell adenoma (3%). In a similarstudy conducted by Guadagni  et al. , 11 Hu¨rthle celladenomas constituted 6.37% of thyroid tumours. Inour study, the ground glass appearance (clearnucleus), pale staining and overlapping of nuclei havebeen accepted as the important histological features of PC of the thyroid and were found in all (100%) cases of PC. Other nuclear features were not consistent. Otherhistological features of PC were also sought, such as70  ⁄    76 (92%) papillary structures with vascular cores,45  ⁄    76 (59%) psammoma bodies. Multilocality, squa-mous, fibrous stoma and metaplasia were seen in31  ⁄    76 (40.8%), 6  ⁄    76 (8%) and 4  ⁄    76 (5%) cases,respectively. Papillary structures were not found in thefollicular variant of PC, and we diagnosed them onnuclear features. Our findings are not consistent withthose of Hake and Dehner, who found nuclear clearingin 83% cases of PC. 12 Of the four major traditionalgroups of thyroid carcinoma, PC and FC are the mostcommon, and other forms (APC and MC) relativelyrare, constituting 3.7% of our cases. In a study by Jensen  et al. , MC constituted 5% of thyroid cancers,with an equal sex ratio. In a study from Saudi Arabia,MC constituted 5.4%. 13 Critical review of WHO classification 1  After a prolonged period of revised WHO criteria forthyroid tumours, some deficiencies of the WHO classi-fication have been pointed out by various authors. Wesuggest that the entity, showing insular, solid, squa-mous differentiation, evidence of mucin or a combina-tion of these features or occupying a positionintermediate between well-differentiated PC, FC andMC and undifferentiated (atypical) carcinomas, shouldbe proposed as PDTC. Immunohistochemistry may helpin further classification. 2  Depending upon the WHO criteria, the diagnosis of PC is now exclusively dependent on the characteristicnuclear features. As a result, most of these tumours aremissed even by experienced pathologists. Moreover,hyperplastic thyroid lesions, FAs and Hashimoto’sthyroiditis may contain cells with clear nuclei resem-bling those of PC. PCs composed entirely of hyperchro-matic cells have been overlooked. 3  In a revised WHO classification, a variant of PC witha focal spindle, insular pattern and giant cell carcinomacomponents should be placed in the PDTC category andits clinical behaviour investigated. 4  We also consider oncocytic carcinoma as a distinctentity because of its different mode of spread. Wesuggest that this category should be kept in a separategroup as in the previous classification.   2009 The Authors. Journal compilation    2009 Blackwell Publishing Ltd,  Histopathology ,  55,  114–132. Correspondence  123  5  MC is a variant of endocrine carcinoma and shouldbe classified according to endocrine carcinoma of lungor gastrointestinal tract into well-differentiated orpoorly differentiated endocrine carcinoma. MC is asso-ciated with hormone secretions and is responsible forcausing hormonal manifestations. Therefore, in thenext WHO classification it should be classified withother endocrine carcinomas for uniformity in diagno-sis, prognostic and therapeutic purposes. Mulazim Hussain BukhariShahida NiaziMuhammad Anwar 1 Aejaz Nasir 2 King Edward Medical University, Lahore, Pakistan, 1 Department of Epidemiology and Preventive Medicine,Kagoshima University, Graduate School of Medical and Dental Sciences, Japan and  2 Department of Pathology, Mofitt Cancer Center,Tampa, FL, USA 1. Nguyen GK, Ginsberg J, Crockford PM. Fine-needle aspirationbiopsy cytology of the thyroid. Its value and limitations in thediagnosis and management of solitary thyroid nodules.  Pathol.Annu.  1991;  26 (Pt 1) ;  63–91.2. Mackenzie EJ, Mortimer RH. 6: Thyroid nodules and thyroidcancer.  Med. J. Aust.  2004;  180;  242–247.3. Bukhari MH, Niazi S, Hanif G  et al.  An updated audit of fineneedle aspiration cytology procedure of solitary thyroid nodule. Diagn. Cytopathol.  2008;  36;  104–112.4. Niazi S, Bukhari MH, Qureshi GR. Morphological evaluation of non neoplastic lesions of the thyroid gland.  Annals of KEMC  2006;  13;  333–335.5. Kumar V, Collins T, Abbas A. The endocrine system (thyroid). InCotran RS, Kumar V, Robbins SL eds.  Robbins pathologic basis of disease , 7th edn. Philadelphia: Saunders, 2004; 1130–1147.6. Baloch ZW, Livolsi VA. Unusual tumors of the thyroid gland. Endocrinol. Metab. Clin. North Am.  2008;  37;  297–310.7. LiVolsi VA, Baloch ZW. Follicular neoplasms of the thyroid:view, biases, and experiences.  Adv. Anat. Pathol.  2004;  11; 279–287.8. Hussain N, Anwar M, Nadia N. Pattern of surgically treatedthyroid disease in Karachi.  Biomedica  2005;  21;  18–20.9. Deveci M, Deveci G, LiVolsi VA. Fine-needle aspiration of follicular lesions of the thyroid. Diagnosis and follow-Up.  Cyto- journal  2006;  3;  9–15.10. Qureshi N, Jaffer R, Ahmed N, Nagi WA. Causes of goiter – a histological analysis.  Biomedica  1996;  12;  54–56.11. Guadagni S, Francavilla S, Agnifili A, De Bernardinis G,Mariani G, Carboni M. Hurthle cell adenoma of the thyroid: in32 consecutive cases.  J. R. Coll. Surg. Edinb.  1996;  41;  246– 249.12. Hapke MR, Dehner LP. The optically clear nucleus. A reliablesign of papillary carcinoma of the thyroid?  Am. J. Surg. Pathol. 1979;  3;  31–38.13. Ahmed I, Malik ML, Ashraf M. Pattern of malignancy in solitarythyroid nodule.  Biomedica  1999;  15;  39–42. Localized leishmanial lymphadenitis:an unusual manifestation of the diseasein an immunocompetent patient  DOI: 10.1111/j.1365-2559.2009.03334.x Sir  : Leishmaniasis describes a globally widespreadgroup of parasitic diseases that are transmitted by thebite of infected female phlebotominei sandflies.  Leish-mania infantum  is the major causative agent in theMediterranean area. 1 It may cause a spectrum of clinical diseases, including cutaneous, mucocutaneousand visceral Leishmaniasis with or without lymph nodeinvolvement. 2,3 Isolated lymphadenitis is uncommon. 4 Here, we report a case of isolated leishmanial lymph-adenitis, an uncommon cause of lymphadenitis thatshould be considered in the differential diagnosis of unexplained lymphadenopathy in endemic countries.A 28-year-old White man presented with anindolent left supraclavicular lymph node of 6 months’duration. Physical examination revealed a 20-mm,mobile, firm adenopathy in the left supraclavicularregion and another one (10 mm) in the left axillaryregion. The rest of the examination was unremark-able. Laboratory results were as follows: white bloodcell count, 7338 leucocytes  ⁄    mm 3 (37% neutrophils,43% lymphocytes). Viral (Epstein–Barr virus, humanimmunodeficiency virus, hepatitis B virus, hepatitis Cvirus, cytomegalovirus) and parasitic (toxoplasmosis)serological tests were negative. Serum protein electro-phoresis was unremarkable. Computed tomographyof the chest, abdomen and pelvis showed somemediastinal lymphadenopathy. The initial clinicalimpression was lymphoma and the supraclavicularlymph node was excised. Imprints with May–Gru¨n-wald–Giemsa stain showed, within the cytoplasm of macrophages, ovoid bodies ranging from 2 to 3  l mwith pale cytoplasm and a darkly stained nucleus(Figure 1A). Histological examination showed follicu-lar lymphoid hyperplasia with considerable variationin size and shape (Figure 1B). The follicles weresurrounded by an ill-defined mantle. Sinuses werefilled with clusters of monocytoid cells. The interfol-licular areas were partially replaced by well-demar-cated, non-caseating granulomas, composed of epithelioid cells and scattered multinucleate giantcells. Numerous ovoid structures measuring 2–3  l min diameter were observed in the cytoplasm(Figure 1C) and, interestingly, in the cytoplasm of some mono- or bi-nucleated cells located within thegerminal centres (Figure 1D). The absence of Bcl-2protein immunoreactivity within germinal centresconfirmed a reactive follicular hyperplasia. The mon-   2009 The Authors. Journal compilation    2009 Blackwell Publishing Ltd,  Histopathology ,  55,  114–132. 124  Correspondence
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