Correspondence

The virtual double-headed microscope:telepathology for all?

Sir: Medline abounds with reports of telepathologytrials. Most claim success, but none has influencedroutine practice for more than a tiny minority ofpathologists. This is probably because the trials alllinked just a few centres, with proprietary and expensivesolutions. A network gains in value in proportion to itssize: the more people you can contact, the more use it is.Consequently we are proposing a ‘trial’ which willinvolve as many diagnostic departments as possible.

The term telepathology covers many disparatetechnologies. At one extreme it has been amplydemonstrated that excellent results can be achieved byremote control of a distant microscope. This can be ofimmense value to very isolated small hospitals for frozensection diagnosis. However, motorized microscopes areexpensive, and this type of referral is largely unneces-sary in the densely populated UK. Perhaps at the otherextreme is the transmission of still digital images. This isused by the AFIP teleconsultation service and can beachieved by E-mail. Producing the images is laborious;the AFIP scheme is rather bureaucratic and there is nofacility for direct interaction between pathologists atseparate sites.

We believe that real-time videoconferencing—in theform which we have called the ‘virtual double-headedmicroscope’—will be of most value in the UK. Discus-sion of difficult cases is likely to be the main use, butclinicopathological conferences, standardization, auditand other applications are likely to follow. Sowter andWells appear to concur with this view, but in 1998 theysuggested that technical developments would first berequired.

We believe that these developments have now beenachieved, or can very soon be expected and are availableat low cost. The main limitation is high-speed networkaccess. This has been enjoyed for years by academicdepartments. However, in the UK, NHSnet is expandingand the service to smaller hospitals is improving. Wherethis is not available or where secure gateways (‘fire-walls’) pose an insurmountable problem, ISDN is nowmuch cheaper than it was, and the new fast ADSLaccess or cable modems will become available to manyparts of the UK from early 2000.

Another requirement identified by Sowter and Wellswas appropriate software which complies with inter-national nonproprietary standards. A new version ofMicrosoft’s NetMeeting was released in mid-1999; it

is sophisticated, it complies with new internationalvideoconferencing standards and it is free. The adop-tion of this ‘open standard’ makes it is possible toestablish a videoconferencing network without beingtied to a single manufacturer and at relatively littlecost.

We have already established a group of specialistpathologists who are equipped for Internet videocon-ferencing and are willing at least to attempt to provideconsultation in this way. We have obtained fundingfrom the UK Department of Health which should besufficient to help around 50 histopathology depart-ments to connect to this scheme, including on-sitetraining. Others will be able to join later, but at theirown expense.

So what is needed to join this ‘national trial’? Mostlaboratories have computers of an adequate specifica-tion and suitable video cameras are usually available,attached to microscopes and used for case conferences.The only additional items needed to establish a basic‘virtual double-headed microscope’ are a video card toconnect the camera to the computer, assistance withestablishing the network links, software and training.We have obtained funding which we envisage will besufficient to provide these ‘missing items’ to the first 50laboratories who contact us expressing an interest injoining this scheme. Such support is limited to UKlaboratories, though as the scheme is based on theInternet we hope also to encourage internationalcollaboration. More information, including legal gui-dance, is available through the website of the BritishDivision of the IAP (HTTP://www.bdiap.org).

We know that there will be problems. Diagnosisfrom computer screens has its own ‘learning curve’and image quality will not be as good as that with a‘real’ microscope, at least initially. We anticipate that,until experience is gained, most ‘telediagnoses’ shouldbe followed by confirmation using conventionalexamination of slides delivered by post. However,pathologists will soon learn the skills of telediagnosis,and image quality and access speed will undoubtedlyimprove in the future. Our aim at this stage is merelyto establish a core network. If it is found to be usefulwe hope that it can grow of its own accord, withminimal supervision—much as the Internet itself hasgrown.

We believe that it is time for histopathologists to stopdabbling their toes in the water, and take the plunge. Wehave established the core of a new network. If itsucceeds, it will enhance the quality and international

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reputation of histopathology in the UK. We invite anyhistopathologist who is interested to contact us todiscuss what is needed to join and to help the network todevelop.

P FurnessJ Rashbass1

Leicester General Hospital,Leicester, and

1Clinical and Biomedical Computing Unit,Cambridge University,

Cambridge, UK

CD34 expression in calcifying fibrouspseudotumours

Sir: Weynand et al. described in Histopathology CD34expression in calcifying fibrous pseudotumour occurringin the peritoneum.1 This result prompted us to performimmunostaining for CD34 (QBEND10, Serotec) on our

series of calcifying fibrous pseudotumours, of which onesoft tissue case2 and four peritoneal cases3 were reportedpreviously. Clinical data are summarized in Table 1. Ninelesions were located on the visceral peritoneum, two inthe soft tissues, and one occurred in the spermatic cord.Histologically, each lesion showed the following typicalfeatures of calcifying fibrous pseudotumour: sharpcircumscription, paucicellular fibrous pattern with fociof lymphoplasmacytic infiltrates, and calcifications of adystrophic or psammomatous type (Figure 1). Thefibroblasts stained with anti-CD34 in nine of 12 cases(Figure 2). The number of immunoreactive cells variedfrom scarce to diffuse (Table 1). Our results, along withthose of Weynand et al., indicate that the calcifyingfibrous pseudotumour may be added to the long listof CD34-positive lesions of soft tissue. CD34-positivephenotype of the fibroblasts is common in collagenousconnective tissues.4 Silverman and Tamsen4 proposedthat such cells can give rise to other types of reactivefibroblasts (myofibroblasts, myxoid fibroblasts, collage-nous fibroblasts) for repair and remodelling of tissue. Webelieve that in the calcifying fibrous pseudotumour the

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Table 1. Case details

Age (years)/Case sex Location Size (mm) CD34

1 71/F Peritoneum 20 ×15 ×15 þ

2 23/F Peritoneum 20 ×25 ×25 ¹

3 53/M Peritoneum 20 ×20 ×10 þ

4 63/M Peritoneum 20 ×20 ×10 þ þ

5 21/F Thigh 40 ¹

6 63/M Peritoneum 10 þ þ

7 57/M Peritoneum 7 þ þþ

8 71/M Peritoneum 10 þ

9 27/F Peritoneum 15 þ þþ

10 19/M Spermatic cord 20 ×20 ×30 þ þþ

11 60/F Peritoneum 5 þ

12 65/F Retroperitoneum 15 ×10 ×10 ¹

F, female; M, male; þ, scarce positivity;þ þ, moderate positivity;þ þ þ, diffuse positivity;¹, negative result.

CD34-positive cells differentiate toward CD34-negativecollagenous fibroblasts.

M ZamecnikM Michal1

L Boudova1

M Sulc2

Department of Pathology,Postgraduate Medical School,

Bratislava, Slovak Republic; and,1Department of Pathology,

Faculty Hospital,Plzen, Czech Republic; and,2Department of Pathology,

General Hospital,Chomutov, Czech Republic

1. Weynand B, Draguet A-P, Bernard P, Marbaix E, Galant C.Calcifying fibrous pseudotumor: first case report in the peritoneumwith immunostaining for CD34. Histopathology 1999; 34; 86–87.

2. Zamecnik M, Dorociak F, Vesely L. Calcifying fibrous pseudotumorafter trauma. Pathol. Int. 1997; 47; 812(L).

3. Kocova L, Michal M, Sulc M, Zamecnik M. Calcifying fibrouspseudotumour of visceral peritoneum. Histopathology 1997; 31;182–184.

4. Silverman JS, Tamsen A. Reply to the letter of M. Zamecnik and M.Michal. Pathol. Res. Pract. 1999; 194; 737–738.

Chromophobe cell renal carcinomas withsarcomatoid areas

Sir: The letter by Mai et al.,1 in the July 1999 issue ofHistopathology, about sarcomatous transformation of achromophobe cell renal carcinoma prompts me toreport two cases with this diagnosis in our files.

The patients were two 77-year-old women. Case 1had a tumour of 55 × 40 × 40 mm located in the middleleft kidney, and case 2 had a tumour of 95 × 90 × 85 mmin the lower pole of the right kidney bulging from thecortical surface. Grossly, both were tan and soft, withwhite firm areas and foci of haemorrhage and necrosis.In case 1, the tumour invaded the perirenal adiposetissue. In case 2, it was limited to the kidney.Microscopically, they were composed of typical chromo-phobe cell areas and foci of spindled cells withpleomorphic nuclei and numerous mitotic features,reaching 20 mitosis by 10 high-power fields in case 1(Figure 1). In both cases, the sarcomatoid componentoccupied less than 25% of the tumour volume. Invasionof medium-sized branches of the renal vein was found inthe two neoplasms.

The immunohistochemical profile was identical in

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Figure 1. Calcifying fibrous pseudotumour showing three basicfeatures: abundant fibrosis, calcifications and lymphoid aggregates(case 10).

Figure 2. Positivity for CD34 is seen in the endothelium of the ves-sels and in the fibroblasts with slender cell shape (case 7).

both tumours, with positivity for cytokeratins (AE1/AE3) in the two components, for epithelial membraneantigen (EMA) in the chromophobe areas and forvimentin in the sarcomatoid areas. The chromophobecomponent was completely negative for vimentin inboth cases.

Case 1 is alive without evidence of disease 50 monthsafter the surgical resection, a surprising evolution for apT3a renal cell carcinoma with sarcomatoid areas. Case2 underwent the nephrectomy only 2 months ago. Shehas had an uneventful postoperative course.

Contrary to what Mai et al.1 assert, their case is notthe first sarcomatous transformation of a chromophoberenal cell carcinoma in the literature. A few cases havebeen reported previously.2–8 In one of these reports,4 ithas been suggested that the chromophobe cells may bethe most frequent epithelial component associated withsarcomatoid areas in renal carcinomas.

There is evidence that the chromophobe cell subtypeis the least aggressive renal cell carcinoma. It is accepted

that the presence of sarcomatoid areas is an unfavour-able prognostic factor in renal cell carcinomas. If thesubtype of epithelial component has influence in theprognosis of the sarcomatoid neoplasms of the kidneyremains to be explored.

JC Tardıo

Department of Pathology,Hospital El Escorial,

Madrid,Spain

1. Mai KT, Veinot JP, Collins JP. Sarcomatous transformation ofchromophobe cell renal carcinoma. Histopathology 1999; 34; 557–559.

2. Mejean A, Codet Y, Droz D, Chretien Y, Vogt B, Dufour B. Carcinomerenal a cellules chromophobes: justification a la chirurgieconservatrice? (Abstract). Progres en Urologie 1995; 5 (Suppl. 5);21A.

3. Hamed G, Perez-Ordonez B, Russo P, Gaudin P, Reuter V.Chromophobe renal cell carcinoma. A clinicopathologic study of51 cases (Abstract). Lab. Invest. 1996; 74; 74A.

4. Akhtar M, Tulbah A, Kardar AH, Ali MA. Sarcomatoid renalcarcinoma: the chromophobe connection. Am. J. Surg. Pathol.1997; 21; 1188–1195.

5. Gomez-Roman JJ, Mayorga-Fernandez M, Fernandez-Fernandez F,Val-Bernal JF. Sarcomatoid chromophobe cell renal carcinoma:immunohistochemical and lectin study in one case. Gen. Diagn.Pathol. 1997; 143; 63–69.

6. Joubert M, Cassagnau E, Boullanger P, Laboisse C, Buzelin F.Variante sarcomatoıde du carcinome renal a cellules chromophobes.A propos de 2 observations. Ann. Pathol. 1997; 17; 392–395.

7. Hirokawa M, Shimizu M, Sakurai T, Terayama K, Manabe T.Sarcomatoid renal carcinoma with chromophobe cell foci. Reportof a case. APMIS 1998; 106; 993–996.

8. Kuroda N, Hayashi Y, Itoh H. A case of chromophobe renal cellcarcinoma with sarcomatoid foci and a small daughter lesion.Pathol. Int. 1998; 48; 812–817.

Intraoperative assessment of sentinel nodesin breast cancer

Sir: I have noted that, in both the article on sentinellymph nodes in breast cancer by van Diest andcolleagues1 and the accompanying commentary byAnderson,2 the statement is made that the sensitivity offrozen section is superior to that of imprint ‘cytology’.The Materials and Methods section of the van Diestarticle states that ‘Imprints were made of all cut surfacesand stained with Quickdiff ’. If I may interpret thisstatement literally, it is of no surprise that the frozensection technique was better, since imprints are anotoriously poor way to screen lymph nodes formetastatic disease. If, on the other hand, the cutsurfaces of the nodes had been scraped with a scalpel

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Figure 1. An area of transition between groups of type III chromo-phobe cells (top) and spindle cells of the sarcomatoid component(bottom).

blade and the cellular material thus obtained smearedon glass slides, air-dried and stained,3,4 the yieldwould probably have been at least as good as—and inmy personal experience better than—that of frozensection, the conservation of time considerable, and thepreservation of tissue for subsequent studies laudable.It is important to compare best technique with besttechnique in evaluating two diagnostic modalities, andintraoperative cytology should not be overlooked onthe basis of experience with the imprint techniquealone.

S G Silverberg

Department of Pathology,University of Maryland,

Baltimore,MD, USA

1. van Diest PJ, Torrenga H, Borgstein PJ et al. Reliability ofintraoperative frozen section and imprint cytological investigationof sentinel lymph nodes in breast cancer. Histopathology 1999; 35;14–18.

2. Anderson TJ. The challenge of sentinel lymph node biopsy.Histopathology 1999; 35; 82–84.

3. Nochomovitz L, Sidawy M, Silverberg SG et al. Intraoperativeconsultation. A Guide to Smears, Imprints and Frozen Sections.Chicago: ASCP Press, 1989: 2–5.

4. Sidawy MK, Silverberg SG. Intraoperative cytology: back to thefuture? (Editorial). Am. J. Clin. Pathol. 1991; 96; 1–3.

Author’s reply

Dr Silverberg is right that our description of the imprintprocedure should be taken literally.1 We made imprintsand have not used the scraping technique. It is indeedimaginable that the scraping technique would provide abetter cell yield, and we agree that this should beevaluated since there are to our knowledge no publishedstudies yet on scraping cytology of sentinel nodes. In theongoing evaluation of the intraoperative procedure inour Department, we will give this technique a try andhope to publish the results in the future.

P J van DiestH TorrengaP Borgstein

R PijpersR P Bleichrodt

F D RahusenS Meijer

Department of Pathology,Free University Hospital,

Amsterdam,The Netherlands

1. van Diest PJ, Torrenga H, Borgstein PJ et al. Reliability ofintraoperative frozen section and imprint cytological investigationof sentinel lymph nodes in breast cancer. Histopathology 1999; 35;14–18.

Myoid cells in the fibrosarcomatous variantof dermatofibrosarcoma protuberans

Sir : In a recent issue of Histopathology, Sanz-Trelles1

proposes that the myoid cells in dermatofibrosarcomaprotuberans with fibrosarcomatous areas (DFSP-FS)are non-neoplastic. The evidence appears to be con-vicing because of the demonstration of the spatialrelationship of myoid cells with walls of vessels in serialsections. However, a recent report of myoid differentia-tion in a metastasis of DFSP-FS by Ohtani et al.2 suggeststhat this differentiation may be neoplastic as well.Ohtani et al. observed actin-positive myoid cellsarranged in a fascicular or sporadic pattern inpulmonary metastasis of DFSP-FS. These cells hadclearly a neoplastic appearance (note Figure 4 of thisreport) different from that of entrapped perivascularsmooth muscle cells, and they lacked any relationshipto the vessels. Probably, the foci of myoid cells inDFSP-FS may be produced by both pathogeneticmechanisms.

M Zamecnik

Department of Pathology,Postgraduate Medical School,

Bratislava,Slovak Republic

1. Sanz-Trelles A. Myoid cells in the fibrosarcomatous variant ofdermatofibrosarcoma protuberans. Are they neoplastic? Histo-pathology 1999; 34; 179–180.

2. Ohtani N, Fukusato T, Tezuka F. Sarcomatous dermatofibrosarc-oma protuberans metastasized to the lung: Preservation of CD34expression in tumor cells. Pathol. Int. 1998; 48; 989–993.

Filiform and signet-ring cells in large B-celllymphoma: ultrastructural interpretation

Sir: In a recent letter to Histopathology,1 a B-celllymphoma was described as having filiform and signet-ring cells. The authors illustrated coarse and inter-digitating processes in their Figure 2a, and provided ahigher power view in Figure 2b which they claim toindicate processes in detail. The image does in fact showprofiles of structures which in another context mightbe reminiscent of obliquely sectioned microvillous pro-cesses. However, their location within an unambiguously

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intramitochondrial compartment indicates that theyare indeed mitochondrial cristae.

This ultrastructural misinterpretation does not alterthe main thrust of the paper since the processes are wellshown in the other figure, but it is nevertheless an error,and trainees in ultrastructural pathology in particularshould be aware of and not confused by this.

B P Eyden

Department of Histopathology,Christie Hospital NHS Trust,

Manchester, UK

1. Jaeger MMM, Santos JN, Jaeger RG et al. Large B-cell lymphomaof the mandible comprising filiform and signet-ring cells. Histo-pathology 1999; 35; 186–188.

Author’s reply

Sir: We have considered whether we overlooked thepresence of two mitochondrial profiles in the upper partof this figure.1 Owing to the depth of focus of theelectron microscope some overlapping occurs. Thus, it isuncertain whether the swollen profiles pointed byarrows represent dilated mitochondrial cristae belong-ing to one of the mitochondrial profiles or other smoothmembrane structures. The disposition of these elements,their closeness to the larger and interdigitating periph-eral processes and their resemblance to the Figure 2b ofanother case of lymphoma with filiform ultrastructure2

led us to consider them true filiform processes.

M M M Jaeger

Universidade de Sao Paulo,Faculdade de Odontologia-Disciplina de Patologia Bucal,

Sao Paulo,Brazil

1. Jaeger MMM, Santos JN, Jaeger RG et al. Large B-cell lymphoma ofthe mandible comprising filiform and signet-ring cells. Histopathology1999; 35; 186–188.

2. Suresh UR, Eyden BP, Banerjee SS, Reeve NL. Primary spleniclymphoma with filiform ultrastructure. J. Clin. Pathol. 1993; 46;570–572.

Predominant Paneth cell differentiation in acolonic adenocarcinoma

Sir: Paneth cells are normally present in the crypts of thesmall intestine, appendix, caecum and proximal rightcolon. In diseases of the colon and rectum, Paneth cellscan be observed in the regenerative mucosa associated

with cronic inflammation, in adenomas and aroundmucinous carcinomas.1 Occurrence of Paneth cells inadenocarcinomas is relatively unusual and tumours withpredominant Paneth cell differentiation are exceptional.

We have recently observed in routine pathologymaterial a case of carcinoma mostly composed of Panethcells, arising in the ascending colon of a 89-year-oldman. The patient presented with iron deficiencyanaemia, remarkable weight loss and signs of bowelobstruction. Endoscopy revealed a large polypoidtumour for which a right hemicolectomy was per-formed. Gross pathological examination showed a50 × 40 mm fungating and centrally ulcerated tumour60 mm distal to the ileocaecal valve. The rest of thecolonic mucosa and the terminal part of ileum appearednormal. Twenty-two lymph nodes were identified inparacolic and mesenteric tissues.

Histologically, the tumour was a diffusely infiltratingDukes’ C2 carcinoma (pT3 pN2), with a well circum-scribed and pushing invasive deep margin and with amoderate peritumoural lymphocytic infiltrate. No inva-sion of muscular extramural veins was found, althoughoccasional intravascular carcinomatous thrombi wereseen. Resection margins were free of tumour. Thetumour cells consisted of a mixed population ofgranular and non-granular cells with both diffuse andglandular growth patterns and with abundant extra-cellular and intracellular mucin formation. Granularcells (Figure 1A) showed microscopic features ofPaneth-cell differentiation and constituted about 60%of the tumoural population in the main bulk of thetumour. They contained coarse refractile stronglyeosinophilic granules arranged diffusely around thenuclei. The granules were PAS positive after diastasetreatment, reddish with Masson’s trichrome andunstained by alcian blue. Granular cells showedmarked variation in the size, shape and number ofgranules with some vesicular nuclei. Non-granular cells(Figure 1B) represented a combination of columnar,goblet and signet ring cells secreting large amounts ofneutral and acid mucins, stainable with PAS, alcian blueand high-iron diamine. Tumour cells with mixedfeatures just between the granular and non-granularcells, i.e. with PAS positive granules and alcianophilmucin, were also found. Mitotic figures were occasion-ally seen among the tumour cells (mitotic index <1/10HPF). Metastatic disease was seen in all regional lymphnodes, showing the same histological features of theprimary neoplasm. Immunohistochemically, the eosino-philic granules were strongly positive for lysozyme. Thisprotein was also identified in non-granular cells, althoughtheir stainability was much weaker (Figure 1C). Nochromogranin A-immunoreactive cells were found.

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MIB-1 antibody revealed 15% of positive cells withnuclear staining.

This additional case of colonic carcinoma withpredominant Paneth cell differentiation tends to confirmthis type of tumour as a definite entity. Paneth cells arefully differentiated cells which play an important role inintestinal antimicrobial defence mechanisms.2 It isdifficult to assess whether the presence of large numbersof Paneth cells in large intestinal carcinomas has aninfluence on prognosis. The very few reported cases,3–6

showed widespread local, lymphatic and vascular inva-sion. Although a Paneth cell rich tumour would mean ahigh degree of differentiation, probably the outcome ofthe disease will depend, as in the other coloniccarcinomas, on the extent of tumour on removal. Ourpatient is alive and well seven months after operation.

Regarding histogenesis, the presence of one or moretypes of cellular differentiation in a colonic carcinomacould be indicative of a multipotential neoplastic stemcell with diverse differentiation capacity. In thisconnection, mixed Paneth–goblet cells observed inlarge numbers in this kind of tumour could representthe result of a faulty differentiation process.

G SerioC Zampatti

U.O. di Anatomia Patologica,Azienda Ospedaliera,

‘Ospedale di Circolo di Busto Arsizio’,Busto Arsizio, VA, Italy

1. Symonds DA. Paneth cell metaplasia in diseases of the colon andrectum. Arch. Pathol. 1974; 97; 343–347.

2. Ouellette AJ. Paneth cells and innate immunity in the cryptmicroenvironment. Gastroenterology 1997; 113; 1779–1784.

3. Subbuswamy SG. Paneth cells and goblet cells. J. Pathol. 1973; 111;181–189.

4. Holmes EJ. Neoplastic Paneth cells. Their occurrence in twoadenomas and one carcinoma of the colon. Cancer 1965; 18;1416–1422.

5. Gibbs NM. Incidence and significance of argentaffin and Panethcells in some tumours of the large intestine. J. Clin. Pathol. 1967;20; 826–831.

6. Shousha S. Paneth cell-rich papillary adenocarcinoma and amucoid adenocarcinoma occurring synchronously in colon: alight and electron microscopic study. Histopathology 1979; 3; 489–501.

Extraskeletal primitive neuroectodermaltumour with massive osteo-cartilaginousmetaplasia

Sir: The extraosseous Ewing’s sarcoma–peripheralprimitive neuroectodermal tumour (ES/pPNET) groupof neoplasms is difficult to diagnose with confidenceby conventional histology alone, since the morphologyof these tumours is characteristically undifferentiatedor exhibits features overlapping with other primitiveneoplasms, such as rhabdomyosarcoma, small cellosteosarcoma, lymphoma–leukaemia, mesenchymalchondrosarcoma and poorly differentiated synovialsarcoma. We report a case of pPNET in soft tissuewith massive metaplastic bone and cartilaginous tissue

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Figure 1. A, neoplastic Paneth cells displaying a strong eosinophilic granular cytoplasm. B, Paneth cells, mucin-containing cells and intermedi-ate cells arranged in a diffuse pattern. C, lysozime stain showing variable immunoreactivity in tumour cells.

where it was difficult to arrive at a conclusive diagnosisbased on light-microscopic findings alone.

A 14-year-old girl with a firm painless mass in theposterior aspect of her left thigh was referred to KyushuUniversity Hospital. Plain radiography showed anirregular calcified tumour in the posterior thigh.Following open biopsy, chemotherapy combined withradiation was performed. After the adjuvant therapy,limb-sparing surgery with a wide margin was carriedout. Five months after the initial operation, chestradiogram revealed lung metastasis in the right upperlobe, and upper lobectomy was then performed.However, she died 4 months later due to multipledisseminated metastases. Autopsy was not carried out.

Grossly, the resected tumour measured about90 × 40 × 30 mm at the greatest diameter and wasbony hard on palpation. The cut surface was tan towhite at the periphery, and massive central necrosis and

focal haemorrhage were present. Microscopically, thetumour was made up of a lobular or sheet-likearrangement of closely packed uniform small roundcells with scant cytoplasm and hyperchromatic nucleipossessing dispersed chromatin and small nucleoli.Prominent mature osseous tissue and immature carti-laginous tissue were recognized between anaplasticsmall round cells (Figure 1A and B). Although thetumour was extensively sampled for histological exami-nation, there were no atypical features within thesebony and cartilaginous tissues. Mitotic figures were seenoccasionally throughout the tumour. In the metastaticsite, distinct Homer–Wright rosettes were frequentlyobserved, although they was not detected in theprimary site. Mature bone trabeculae and cartilaginoustissue were also present in the metastatic lesion.Periodic acid–Schiff staining failed to reveal intracyto-plasmic PAS-positive granules in the small round cells.

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Figure 1. A, The tumour cells have scanty cytoplasm and hyperchromatic nuclei, arranged in solid nests between mature bone trabeculae.There are no atypical features within the bone-producing cells and osteoblastic rimming is evident around the bone trabeculae. B, Immaturecellular cartilaginous tissue with mineralization is also recognized close to the bony structure. Nuclear pleomorphism and mitotic figures arenever detected in these chondrocytes.

Immunohistochemically, most of the small roundtumour cells in both the primary and metastatic siteshowed a diffusely and intense cell membranousstaining for O-13 antibody. Cytogenetic analysis wasperformed on 25 G-band metaphases after a 10-dayprimary culture. An abnormal chromosomal karyotype:57, X, ¹X, þ 2, þ 4, þ 5, þ 8, t(11; 22)(q24; q12), þ 13,þ 14, þ 15, þ 17, þ 18, þ 20, þ 21, þ r (Figure 2) wasfound in 18 cells, whereas the remaining seven cells hada normal female karyotype of 46, XX. Reversetranscription polymerase chain reaction (RT-PCR) forthe EWS/Fli-1 fusion gene1 shows a 330-bp geneproduct in both the primary and the metastatictumour. A subsequent sequence analysis of thePCR product confirmed it to be the type 1 fusiontranscript.

Histologically, extraskeletal osteosarcoma, synovialsarcoma and mesenchymal chondrosarcoma shouldbe distinguished. Extraskeletal osteosarcoma is a raresoft tissue tumour characterized by malignant osteoidproduction.2 However, there were no atypical features

within the bone or osteoid-forming cells in thistumour. Mesenchymal chondrosarcoma exhibits acharacteristic bimorphic pattern composed of undiffer-entiated rounded, oval or spindle-shaped cells andnodules of well-differentiated, benign-appearing carti-laginous tissue frequently with ossification or calcifi-cation. CD99 immunoreactivity3 and reciprocaltranslocation (t11;22)(q24;q12)4 have been reportedin mesenchymal chondrosarcoma, suggesting that thischondrogenic tumour belongs to the wide group oft(11;22) small round cell tumours. In this case, theosseous component was predominant compared to thecartilaginous tissue, and bone formation was observedat the periphery of the cartilage when they were presenttogether. On the other hand, in mesenchymal chon-drosarcoma, calcification or bone formation are usuallyobserved within the central portion of the cartilaginousnodule.

Milchgrub et al.5 recently reported extensive osteoidand bone formation in synovial sarcoma. In their seriesof four cases, cartilaginous differentiation was also

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Figure 2. The cultured tumour cells show a chromosomal abnormality, 57, X, -X, þ 2, þ 4, þ 5, þ 8, t(11; 22)(q24; q12), þ 13, þ 14,þ15, þ 17, þ 18, þ 20, þ 21, þ r.

recognized in one case. In the current case, no tumourcells showed immunoreactivity for epithelial markerssuch as cytokeratin and epithelial membrane antigen.Furthermore, karyotypic analysis revealed t(11;22)translocation instead of t(X;18)6 which is the specificchromosomal aberration in synovial sarcoma. Ourmolecular analyses also failed to detect the SYT-SSXfusion transcript in this case.

In summary, we describe an unusual small round celltumour with reactive massive bone and cartilage forma-tion mimicking small cell osteosarcoma, which wasfinally diagnosed as an extraskeletal primitive neuroecto-dermal tumour with massive osteo-cartilaginous meta-plasia according to histological, immunohistochemical,cytogenetic and molecular analyses.

Y OdaY Kinoshita

S TamiyaY Iwamoto1

M Tsuneyoshi

Department of Anatomic Pathology, andthe 1Department of Orthopaedic Surgery,

Graduate School of Medical Sciences,Kyushu University,

Fukuoka, Japan

1. Delattre O, Zucman J, Plougastel B et al. Gene fusion with an ETSDNA-binding domain caused by chromosome translocation inhuman tumours. Nature 1992; 359; 162–165.

2. Jensen ML, Schumacher B, Jensen OM, Nielsen OS, Keller J.Extraskeletal osteosarcomas. A clinicopathologic study of 25 cases.Am. J. Surg. Pathol. 1998; 22; 588–594.

3. Granter SR, Renshaw AA, Fletcher CD, Bhan AK, Rosenberg AE.CD99 reactivity in mesenchymal chondrosarcoma. Hum. Pathol.1996; 27; 1273–1276.

4. Sainati L, Scapinello A, Montaldi A et al. A mesenchymalchondrosarcoma of a child with the reciprocal translocation(11;22)(q24;q12). Cancer Genet. Cytogenet. 1993; 71; 144–147.

5. Milchgrub S, Ghandur-Mnaymneh L, Dorfman HD, Albores-Saavedra J. Synovial sarcoma with extensive osteoid and boneformation. Am. J. Surg. Pathol. 1993; 17; 357–363.

6. Turc-Carel C, Dal Cin P, Limon J, Li F, Sandberg AA. TranslocationX;18 in synovial sarcoma. Cancer Genet. Cytogenet. 1986; 23; 93.

Corrigendum

Histopathology 1999; 35; 476–477

Clear cell change in colonic adenocarcinoma: anequally unusual finding

The authors of this correspondence are J Furman andG Y Lauwers.

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