multinodular pleural involvement in aggressive systemic mast cell disease

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Langerhans cell histiocytosis associated withpapillary carcinoma of the thyroid

Sir : The case reported by Safali et al.1 of Langerhans cellhistiocytosis (LCH) occurring in lymph nodes draining apapillary carcinoma of the thyroid is of great interest tous as we have encountered a similar case.

A 22-year-old woman presented with a 2-monthhistory of a lump in the neck. A left thyroid lobectomywas performed for a papillary carcinoma. It showed noLangerhans cell or eosinophil infiltrate.

Two months later she re-presented with a painfullump in the left posterior triangle. A lymph node 12 mmacross was removed. Histology showed filling of thesinuses by cells with large, convoluted vesicular nuclei,associated with numerous eosinophils. These cellsstained positively with CD68, S100 and placental alka-line phosphatase and were regarded as characteristic ofLCH. No metastatic carcinoma was identified.

The patient was treated with radioiodine and remainswell, two-and-a-half years since the removal of her lymphnode. The patient reported by Schofield et al.2 wasknown to have been well at 1 year, also after treatmentwith radioiodine, but was then lost to follow-up.

Our case is similar to that of Safali et al. in that theLCH involved draining lymph nodes some distance froma papillary carcinoma. This, and the apparentlyfavourable clinical course, suggest Langerhans cellproliferation to be a reactive phenomenon in thissituation.

R.LindleyR.Hoile

J.Schofield*M.Ashton-Key†

Departments of Pathology and Surgery,Medway Hospital,

Departments of Pathology,*Maidstone Hospital,

Maidstone, and†Brighton Hospital,

Brighton, UK

1. Safali M, McCutchen JM, Wright DH. Langerhans cell histocytosisof lymph nodes draining a papillary carcinoma of the thyroid.Histopathology 1997; 30; 599–603.

2. Schofield JB, Alsanjari NA, Davis J, Maclennan KA. Eosinophilicgranuloma of lymph nodes associated with metastatic papillarycarcinoma of thyroid. Histopathology 1992; 20; 181–183.

Multinodular pleural involvement inaggressive systemic mast cell disease

Sir : Systemic mast cell disease (SMCD) is characterizedby an abnormal proliferation of mast cells that infiltratemost often the skin, bone marrow, spleen, liver andlymph nodes1. There are very rare reports of lunginfiltration by mast cells but we could not find anyreport documenting pleural infiltration by mast cellsalthough there are rare descriptions of pleural effusionsin SMCD2. We describe a case of SMCD in which apleural effusion was an important clinical manifesta-tion. Pleuroscopy and pleural biopsies revealed apeculiar pattern of mast cell infiltration.

The patient was a 68-year-old man who presentedwith a 6-month history of serous rhinorrhoea, pruriticskin lesions, increasing girth, peripheral oedema andweight loss (10 kg). On examination, lesions of urticariapigmentosa, a left pleural effusion, ascites and oedemaof the legs were present. The CT scan showedhepatosplenomegaly and retroperitoneal lymphadeno-pathy. Laboratory data revealed leucocytosis witheosinophilia, prolongation of the prothrombin time,hypocholesterolemia and a high serum histamine level.

Histological examination of a skin lesion, an iliaccrest bone marrow biopsy and a needle liver biopsyshowed extensive mast cell infiltration confirming thediagnosis of SMCD. The overall picture corresponds tothe aggressive SMCD (non-leukaemic) category asdefined by Travis et al.1.

To clarify the cause of the large and rapidly recurrentpleural effusion that caused severe respiratory discom-fort, a left thoracoscopy was performed. After drainageof 1500 ml of a sero-sanguinious fluid, endoscopicexamination revealed small nodules on the costalsurface of the anterior parietal pleura located alongsome of the lower intercostal spaces. They were dark-brown and surrounded by intense hyperaemia (Figure1). Histological examination of the pleural nodules(Figure 2) showed a dense cellular infiltration with paleand round cellular aggregates standing out at low power.These aggregates were mostly composed by histiocytoidcells with a clear to slight eosinophilic, ill-defined cyto-plasm and round to reniform nuclei with inconspicuousnucleoli. In the cytoplasm there were a variable numberof granules that stained metachromatically withtoluidine blue or Giemsa stain and bright red with theLeder’s reaction for naphthol-chloroacetate esterase.These characteristics identify these cells as mast cells.Mast cell aggregates were surrounded by eosinophils,lymphocytes and condensed collagen fibres. They were

Histopathology 1998, 32, 180–189

q 1998 Blackwell Science Limited.

similar to those identified in bone marrow and liversamples.

A pleurodesis was performed and the general status ofthe patient temporarily improved with the administration

of ketotifen3. The patient died 8 months later, after theappearance of multiple bilateral pulmonary nodules onchest X-ray. At autopsy the whole picture suggested thelymphadenopathic form of SMCD4. The pulmonarynodules were due to caseating tuberculosis. There wasno mast cell infiltration nor fibrosis in the underlyinglung. The microscopic examination of the thick scarthat resulted from pleurodesis did not disclose anyabnormal mast cell infiltration nor epithelioid granulo-mas, but only diffuse fibrosis. Mast cell infiltration wasnot found in the contralateral pleura, the pericardiumor the peritoneum.

Pleural biopsies with the kind of lesions we describedmay cause difficulties in interpretation. Histiocytoidmast cells in H & E-stained sections and the propensityof immature mast cells to form aggregates simulatinggranulomas at low power, may lead to the diagnosis of agranulomatous disease. The abundance of eosinophilsmay suggest histiocytosis X or the more commonreactive eosinophilic pleuritis. The diagnosis of masto-cytosis is suggested by the presence of the histiocytoidand fusiform cells grouped and mixed together as well assurrounded by eosinophils, lymphocytes and, fre-quently, by collagen fibres. The use of the appropriatestains, e.g. toluidine blue, Giemsa, or Leder’s reaction,will confirm the diagnosis.

We found a single reported case of SMCD in whichascites was attributable to histological confirmed diffuseinfiltration of the peritoneum by mast cells5. To the bestof our knowledge this is the first report of multinodularpleural involvement in SMCD. It remains to be clarified ifthis is an isolated case or if this kind of infiltration ismore frequent or exclusively found in the type of SMCDthat affected this patient.

A.FernandesC.Ferreira

J.VieiraP.Povoa

J.Ducla-Soares

Departments of Pathology, Pneumology and Medicine 3,Santa Maria Hospital

Lisbon, Portugal

1. Travis WD, Li C-Y, Bergstralh EJ, Yam LT, Swee RG. Systemic mastcell disease: Analysis of 58 cases and literature review. Medicine1988; 67; 345–368.

2. Avila NA, Worobec AS, Ling A, Hijazi Y, Metcalf DD. Pulmonaryand ovarian manifestations of systemic mastocytosis. Am. J.Roentgenol. 1996; 166; 969–970.

3. Povoa P, Ducla-Soares J, Fernandes A, Palma-Carlos AG. A case ofsystemic mastocytosis: therapeutic efficacy of ketotifen. J. Int. Med.1991; 229; 475–477.

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q 1998 Blackwell Science Ltd, Histopathology, 32, 180–189.

Figure 1. Endoscopic view of the parietal pleura. The nodules arelocated along an intercostal space and surrounded by intensehyperaemia.

Figure 2. a, Biopsy of a pleural nodule showing pale granuloma-likecellular aggregates and lymphocytic aggregates (H & E). b, Theaggregates are mainly composed by histiocytoid mast cells with avariable density of metachromatic granules in their cytoplasm(Giemsa).

4. Meggs W, Friedman MM, Kramer N, Metcalfe DD. Lymphadeno-pathic mastocytosis with eosinophilia (abstract). Clin. Res. 1985; 3;162A.

5. Yam LT, Chan CH, Li CY. Hepatic involvement in systemic mast celldisease. Am. J. Med. 1986; 80; 819–826.

Ovarian atypical endometriosis

Sir : I read with great interest the study on atypicalendometriosis by Fukunaga et al.1. I completely agreewith their assertion that the frequency of atypicalendometriosis in my study2 was very high due to thereferral nature of the AFIP material. In fact, as indicatedin my study, the cases of atypical endometriosis weredrawn from consecutive consultations over an 11-yearperiod, while the control group consisted of consecutiveconsultation cases of endometriosis from a 2-yearperiod. The rate of atypical endometriosis is probablyin the range of 1.7% to 3.6% as reported by Fukunagaet al.1 and Czernobilsky & Morris3. The criteria used byFukunaga et al. for atypical endometriosis were notidentical to those used in my study, and the annualizedrisk of development of carcinoma in the two studieswere notably different: 10% per year and 0.6% per year,respectively. However, the number of patients develop-ing carcinoma are too small for meaningful statisticalanalysis. In Fukunaga et al.’s study, one of four patientswith atypical endometriosis developed carcinoma after2.5 years of follow-up, while one of 20 patients in mystudy with either complex atypical hyperplasia or ‘earlycarcinoma’ developed clinically evident endometrioidadenocarcinoma after 8.6 years of follow-up (oneadditional patient in my study developed a Mullerianmucinous borderline tumour, a clinically benigntumour4). I agree with these investigators that atypicalendometriosis possesses a premalignant potential,although currently available data are insufficient toestimate the precise magnitude of the risk of carcinoma.Therefore, clinical follow-up may be of value in the rarepatient with atypical endometriosis1,2, exclusive ofthose patients with the more common reactive/degen-erative type of cytologic atypia in epithelium liningovarian endometriotic cysts2. It is also worth empha-sizing the importance of thorough histological samplingof the available tissue when significant atypia orhyperplasia is identified in endometriotic tissue2.

J.D.Seidman

Department of Pathology,Washington Hospital Centre,

Washington, DC, USA

1. Fukunaga M, Nomura K, Ishikawa E, Ushigome S. Ovarian atypical

endometriosis: its close association with malignant epithelialtumours. Histopathology 1997; 30; 249–255.

2. Seidman JD. Prognostic importance of hyperplasia and atypia inendometriosis. Int. J. Gynecol. Pathol. 1996; 15; 1–9.

3. Czernobilsky B, Morris WJ. A histologic study of ovarianendometriosis with emphasis on hyperplastic and atypicalchanges. Obstet. Gynecol. 1979; 53; 318–323.

4. Rutgers JL, Scully RE. Ovarian mullerian mucinous papillarycystadenomas of borderline malignancy: a clinicopathologicanalysis. Cancer 1988; 61; 340–348.

Pilomatrixoma of the ovary: a rare variant ofmature teratoma

Sir : Secondary development of neoplasms in any of thethree germinal layers in mature teratomas is a rareevent. Only a few examples of secondary benigntransformations have been published1. We present aunique case of an ovarian pilomatrixoma, a benigntumour probably developed from a mature teratomawith ectodermal differentiation.

A 53-year-old woman presented with irregularvaginal bleeding after several years of hormone treat-ment in the menopause. An endometrioid adenocarci-noma was diagnosed in the corpus uteri (FIGO stage IB).No vascular invasion or metastases were found, and thepostoperative course was uneventful. An incidentalfinding in the left ovary was a firm, solid and whitishtumour measuring 30 mm in largest diameter. Theovarian capsule was intact and the tube was normal.Histological examination showed a fairly circumscribedlesion with coalescent nodules of eosinophilic material,surrounded by giant-cells of the foreign body-type(Figure 1). Typical ghost or shadow epithelial cellswere identified in all eosinophilic areas (Figure 2). Areasof basaloid differentiation were not found, and mitoseswere not seen. Minor areas of dystrophic calcification

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Figure 1. Irregular islands of ghost cells with giant cells. Minorareas of calcification (arrow) are seen.

were present. A slight inflammatory reaction was foundin the loose intervening matrix. By serial sectioning ofthe tissue, no other tissue types were found.

Pilomatrixoma is a benign appendage tumour of theskin2. In the skin, a transition zone between basaloidmatrix cells and cortex cells in the pilomatrixoma isoften found in early neoplasms. In later lesions, thecharacteristic shadow cells of the cortex predominate.Basaloid areas were not found in our case, consistentwith a late neoplasm with low growth potential.

Occasionally, teratomas have a dominant componentof a single layer or tissue type. A transformed tissuecomponent, both benign and malignant, may overgrowand obscure other tissue types originally present in theteratoma. This may explain the lack of other teratoidelements than the pilomatrixoma in the present case.The differential diagnosis should include degenerativechanges in a monodermal cystic teratoma of epidermoiddifferentiation. Epidermoid cysts are filled with amor-phous keratotic material which may undergo calcifica-tion. Islands of ghost cells throughout the lesion, as inpilomatrixomas, is unlikely in these cystic tumours.

The main disease of our patient was a carcinoma ofthe endometrium. Endometrioid carcinomas may showareas of extensive squamous metaplasia and foreignbody giant cell reaction, both as a primary tumour or asmetastatic lesions to the ovary. In the case of ametastatic lesion, one would expect adjacent areas ofglandular differentiation. Ghost squamous cells withoutviable tumour components have been described in theovaries of patients with endometrial carcinomas3, butlesions such as peritoneal keratin granulomas aregenerally small and superficially located.

Fang et al.4 recently reported an adenosquamouscarcinoma with pilomatrixoma-like areas in the ovaryof a 48-year-old woman. They considered this malig-nant neoplasm as derived from foci of endometriosis,and did not discuss the possibility of a teratoidcomponent. Their lesion may have been an example ofa malignant transformation in a mature teratoma,originally containing the same benign dermoid ele-ments as in our case. Although no other teratoidelements were found, we consider the most likely originof this pilomatrixoma-like lesion to be a matureteratoma. The case represents a new variant of amature monodermal teratoma of the ovary.

G.C.AlfsenE.H.Strøm*

Departments of Pathology,The Norwegian Radium Hospital and

*Ulleval Hospital,Oslo, Norway

1. Russell P, Bannatyne P. Teratomas—mature. In Surgical Pathologyof the Ovaries. Edinburgh: Churchill Livingstone, 1989; 416–425.

2. Murphy GF, Elder DE. Non-melanocytic tumors of the skin. In RosaiJ and Sobin LH eds. Atlas of Tumor Pathology, fascicle 1, 3rd series.Washington: Armed Forces Institute of Pathology, 1991; 142–144.

3. Kim K-R, Scully RE. Peritoneal keratin granulomas with carcin-omas of endometrium and ovary and atypical polypoid adeno-myoma of endometrium. A clinicopathological analysis of 22 cases.Am. J. Surg.Pathol. 1990; 14; 925–932.

4. Fang J, Keh P, Katz L, Rao MS. Pilomatricoma-like endometrioidadenosquamous carcinoma of the ovary with neuroendocrinedifferentiation. Gynecol. Oncol. 1996; 61; 291–293.

Prostate specific antigen and the salivarygland

Sir : A recent article by Simpson and Skalova describedtwo cases of metastatic carcinoma of the prostatepresenting as a parotid tumour1. They referred to astudy by van Krieken2, describing positive staining byprostate markers in tumours of the salivary glands.Simpson and Skalova were unaware of other studiesreproducing these results.

I would like to draw attention to a study reportedsome 12 years ago3, describing staining of striated ductcell of the salivary gland and myeloid cells withprediluted (kit) rabbit antisera to prostate specificantigen. One pleomorphic adenoma was also positive.Understandably this study was reported in a localscientific journal and would probably not appear inmost computerized literature searches.

This aberrant staining was found to disappear when

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Figure 2. An island of typical ghost cells. The inflammatory reactionin the stroma is dominated by small lymphocytes.

the antisera was further diluted: 1/16 for salivary glandstaining and 1/8 for myeloid cells. Positive stainingremained in a poorly differentiated prostatic carcinomaat these dilutions. The cross-reacting antibodies weretherefore found to be a minor component of theantibody preparation. Since then, this staining hasfailed to recur with subsequent lots of antibody. Thisalso has been found by Simpson and Skalova1.

It is therefore important to routinely test new lots ofantiserum on normal tissues to check for unexpectedstaining. Salivary gland and bone marrow (myeloidcells) should be included in the quality control of PSAantisera.

T.Henwood

Department of Anatomical Pathology,Royal Prince Alfred Hospital,

Camperdown, Australia

1. Simpson RHW, Skalova A. Metastatic carcinoma of the prostatepresenting as parotid tumour. Histopathology 1997; 30; 70–74.

2. Van Krieken JHJM. Prostate marker immunoreactivity in salivarygland neoplasms: a rare pitfall in immunohistochemistry. Am. J.Surg. Pathol. 1993; 17; 410–414.

3. Scott GS, Henwood AF. Crossreactivity in immunoperoxidase:prostate specific antigen. Aust. J. Med. Lab. Sci. 1984; 5; 73–75.

Monophasic sarcomatoid carcinoma of thebreast

Sir : Monophasic sarcomatoid carcinoma of the breast isa rare tumour which may be mistaken for a primarysarcoma. We have recently encountered an example ofthis tumour and wish to emphasize the value of immuno-chemistry in establishing the correct diagnosis. We alsocomment on the need for consistent terminology indescribing this tumour.

A 38-year-old woman presented with a left-sided

184 Correspondence


Figure 1. Monotonous, rather bland, spindle cells, a, alternating with areas of pleomorphic sarcoma-like cells in a myxoid stroma b, (H & E,× 310).

breast lump. A discrete mobile lump was palpable andradiological examination showed a circumscribedlesion. Fine needle aspiration cytology yielded a cellularsample of malignant spindle cells. A diagnosis ofphyllodes tumour was suggested and the patientunderwent excisional biopsy of the lesion. The breasttissue measured 60 × 60 × 30 mm and contained acircumscribed 30 mm firm white nodule with amucoid cut surface. The entire tumour was processedand haematoxylin and eosin (H & E) examination(Figure 1) revealed a circumscribed, unencapsulatedtumour composed of monotonous spindle cells alter-nating with areas of highly pleomorphic sarcoma-likecells arranged in a partly myxoid stroma. Mitotic figureswere frequent (6/10 HPF). No in-situ carcinoma orinvasive carcinoma of conventional ductal or squamoustypes was identified. Immunohistochemistry was per-formed with the avidin–biotin method using antibodiesagainst low molecular weight keratin (CAM5.2, BectonDickinson; 92-0005), broad spectrum keratin (MNF116,Dako Ltd; M821), high molecular weight keratin (DakoLtd; A575), HMFG1 and 2 (Unipath Ltd), vimentin(Dako Ltd; M7020), alpha smooth muscle actin (Sigma;A2547), desmin (Euro Diagnostica; MDE11), and S100(Dako Ltd; Z311). The tumour cells were stronglyvimentin positive and the majority of cells also showedpositivity with antibodies to high molecular weight andbroad spectrum keratin (Figure 2). The tumour cellswere negative for all other antibodies tested includinglow molecular weight cytokeratin (CAM5.2). In view ofthe keratin positivity the findings were interpreted asmonophasic sarcomatoid carcinoma. No residualtumour was found in the subsequent mastectomyspecimen and 21 axillary lymph nodes were negative.

Sarcomatoid carcinoma of the breast is known by avariety of names including metaplastic carcinoma,spindle cell carcinoma, and carcinoma with pseudo-sarcomatous metapasia. Most reported cases areexamples of biphasic sarcomatoid carcinoma in whichfoci of squamous or ductal carcinoma are identifiablewithin a sarcomatous tumour. In these cases thepresence of conventional carcinoma alerts the pathol-ogist to the diagnosis which can be confirmed usingimmunohistochemistry or electron microscopy. In ourcase no conventional carcinoma was identified despiteexamining the entire tumour histologically. The lightmicroscopic features were suggestive of a primarysarcoma and the strong tumour cell positivity forvimentin and the complete absence of staining withthe CAM5.2 antibody to low molecular weight keratincould have led to an erroneous diagnosis. The correctdiagnosis of monophasic sarcomatoid carcinoma wasestablished using antibodies to high molecular weight

and broad spectrum keratin. This experience is con-sistent with the results of other workers who foundpositive staining with low molecular weight keratin tobe less common than positive staining with antibody tohigh molecular weight keratin in the sarcomatouscomponent of biphasic tumours3.

The clinical behaviour of sarcomatoid carcinoma isnot well documented. Tumour size appears to beimportant1,4 and it has also been suggested that thesetumours have a high potential for distant metastasesalthough frequently lymph node negative1,5. Thepaucity of information on the likely biological courseof this uncommon tumour is exacerbated by theplethora of terms used to identify it and by the inclusionof pure squamous tumours and ductal carcinomas withsquamous differentiation in discussions of so calledmetaplastic carcinoma6. In our view those tumoursshould be identified separately and tumours composedpartly or exclusively of sarcomatous cells of epithelialderivation classified as sarcomatoid carcinoma as

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Figure 2. Tumour cells showing positive staining with antibody tobroad spectrum keratin (arrows) confirming the epithelial nature ofthe tumour (MNF 116, × 310).

defined by Foschini2. The term ‘sarcomatoid’ permits adegree of cellular pleomorphism not traditionallyafforded by the term ‘spindle cell’ and is also preferableto ‘metaplastic’ which seems inappropriate to describe avariation in the morphological appearances of amalignant tumour.

J.L.OstrowskiK.Horgan*T.Krausz†

C.M.Quinn

Departments of Histopathology and *Surgery,The General Infirmary at Leeds,

Leeds, and†Department of Histopathology,

Royal Postgraduate Medical School,Hammersmith Hospital,

London

1. Wargotz ES, Deos PH, Norris HJ. Metaplastic carcinomas of thebreast: II Spindle cell carcinoma. Hum. Pathol. 1989; 20; 732–740.

2. Foschini MP, Dina RE, Eusebi V. Sarcomatoid neoplasms of thebreast: Proposed definitions biphasic and monophasic sarcomatoidmammary neoplasms. Semin. Diagn. Pathol. 1993; 10; 128–136.

3. Eusebi V, Cattani MG, Ceccarelli C, Lamovec J. Sarcomatoidcarcinomas of the breast: an immunohistochemical study of 14cases. Prog. Surg. Pathol. 1989; 10; 83–99.

4. Gutman H, Pollock RE, Janjan NA, Johnston D. Biologic distinctionsand therapeutic implications of sarcomatoid neoplasia of epithelialcarcinoma of the breast. J. Am. Coll. Surg. 1995; 180; 193–199.

5. Christensen L, Schiodt T, Blichert-Toft M. Sarcomatoid tumours ofthe breast in Denmark from 1977 to 1987. A clinicopathologicaland immunohistochemical study of 100 cases. Eur. J. Cancer 1993;29; 1824–1831.

6. Tavassoli FA. Classification of metaplastic carcinomas of the breast.Pathol. Annu. 1992; 27; 89–119.

Pituitary corticotroph adenoma in a primaryenlarged empty sella turcica

Sir : The current pathological literature includes twodescriptions of corticotroph adenoma within anenlarged empty sella (EES)1,2; this report adds a third.

A 54-year-old Afro-Caribbean woman was referred tohospital with breathlessness, exertional dizziness andreduced exercise tolerance. There was a history of asthma,iron deficiency anaemia and chronic hypertension;prescribed drugs included captopril, prochlorperazine,ferrous sulphate and salbutamol. Electrocardiographyshowed sinus tachycardia, and a chest radiographshowed bilateral perihilar masses. There were marginalelevations of creatinine, total protein and glucose. Theclinical differential diagnosis was of sarcoidosis ormalignancy. The patient died suddenly the morningafter admission.

At autopsy, the subject was noted to be markedly

obese, weighing 106.2 kg, but not obviously Cushing-oid; she was 1.62 m tall. There was moderate leftventricular hypertrophy, massive recent pulmonaryembolism and venous thrombosis in the right leg.There was no tumour or sarcoidosis in any organ, and

186 Correspondence


Figure 1. Sagittal section through the centre of the pituitary gland.

Figure 2. Immunohistochemical stains of pituitary adenoma andadjacent normal pituitary tissue. a, Image taken of a section stainedwith an anti-ACTH antibody and photographed at low power; theadenoma is seen at the top and on the right-hand side of the frame.The pale tissue within the adenoma, partly separating it from thenormal tissue, is scar tissue. b,c, High-power images of the samearea, stained with an anti-ACTH antibody (b) and an anti-TSH anti-body (c); the adenomatous tissue is on the right in both images.

no lesion to explain the radiographic findings. The sellaturcica was expanded to a regular bowl 22 mm indiameter and 10 mm in depth, with pituitary tissueplastered evenly around the wall (Figure 1). Theanterior end of the pituitary was microscopicallyhealthy, with prolactin, follicle stimulating hormone,luteinizing hormone, growth hormone, thyrotrophinand corticotroph cells in normal numbers, but centrally,there was a monomorphic mass of corticotroph cellsabutting onto the pars intermedia (Figure 2). This massshowed focal scarring, but had a well-defined outline;there was almost complete obliteration of the normalreticulin pattern, indicating an adenoma rather thanhyperplasia. The adrenal cortices were of normalthickness on stage micrometry.

An empty sella is defined as one partially orcompletely filled with cerebrospinal fluid, whether ornot enlarged. Empty sellae without enlargement arecommon, representing a normal anatomical variant3.EES is pathological, and is described as primary in theabsence of previous surgery or radiation therapy. Mostprimary EES are found in obese, hypertensive, middle-aged women, in whom pituitary function tests arenormal; histology generally demonstrates normal pitui-tary parenchyma1,4. Previous reports describe thetrans-sphenoidal removal of a corticotroph micro-adenoma from an empty sella, thus relieving Cushing’sdisease1, and the incidental discovery of a corticotrophadenoma in an empty sella at autopsy2. Both patients,like the subject of this report, were obese, middle-aged,hypertensive females.

The pathogenesis of primary EES remains conten-tious3. The established view is that the pituitary isdistorted by pressure from above, such as persistentpulsation through a defective sellar diaphragm1. Thereis, however, growing support for the opinion that thecause is silent infarction of a pituitary adenoma, at leastsometimes5: an empty sella, in the absence of anadenoma, does not enlarge after first radiologicaldetection3.

Patients whose empty sellae are accompanied byendocrine dysfunction often have hyperprolactinaemia,but few have prolactinomata. In one series, eight caseswere studied histologically, revealing only one adenoma;the residual pituitary was always histologically normal4.This confirms that an empty sella may arise withoutprimary pituitary disease: the coexistence of a pituitaryadenoma and an empty sella does not necessarilyindicate that one led to the other2.

The associations between obesity and the endocrinesystem are complicated, and the strong link betweenprimary EES and obesity has attracted comment. Recentdemonstrations of a negative feedback loop between

adipose tissue and the hypothalamus, mediated byleptins6, indicate that disruption of this loop may lead toobesity. I would speculate that damage to the hypo-thalamus, or to its connections with the pituitary,occurs in EES, and that this represents such a disruptionof negative feedback.

AC K N O W L E D G E M E N T S

I thank Professor Tony Heagerty for permission toreport the clinical features of this case, Lynn Stephensonand Graham Bigley for performing the immunohisto-chemistry, and Jane Crosby and Wilf Hill de Vries forphotographic assistance.

E.W.Benbow

Department of Pathological Sciences,University of Manchester,

Manchester, UK

1. Ganguly A, Stanchfield JB, Roberts TS, West CD, Tyler FH.Cushing’s syndrome in a patient with empty sella turcica and amicroadenoma of the adenohypophysis. Am. J. Med. 1976; 60;306–309.

2. Ho K-L. Coexistence of primary empty sella and silent corticotrophadenoma. Mod. Pathol. 1996; 9; 521–525.

3. Bjerre P. The empty sella. A reappraisal of etiology andpathogenesis. Acta Neurol. Scand. 1990; 82(Suppl. 130): 1–24.

4. Gharib H, Frey HM, Laws ER, Randall RV, Scheithauer BW.Coexistent primary empty sella syndrome and hyperprolactinaemia.Report of 11 cases. Arch. Intern. Med. 1983; 143; 1383–1386.

5. Robinson DB, Michaels RD. Empty sella resulting from thespontaneous resolution of a pituitary macroadenoma. Arch.Intern. Med. 1992; 152; 1920–1923.

6. Sørensen TIA, Echwald SM, Holm J-C. Leptin in obesity. Br. Med. J.1996; 313; 953–954.

Giant cell angiofibroma of the mediastinum

Sir : The term ‘giant cell angiofibroma’ was coined byDei Tos et al.1 in 1995 to describe a distinctive orbitaltumour in adults. This neoplasm shows histologicalappearances intermediate between, but distinct from,solitary fibrous tumour and giant cell fibroblastoma ofsoft tissue. A case arising in the posterior mediastinumis described.

The patient was a 62-year-old female who presentedwith a rapid swelling of the neck and respiratory pain.Physical examination, computed tomography andmagnetic resonance imaging showed a posteriormediastinum mass located between the upper part ofthe oesophagus and cervical vertebrae. Tumourremoval was attempted in vain because of haemor-rhage. The tumour measuring 50 × 30 × 20 mm waswell demarcated, white, and soft with cystic changes. A

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biopsy was done. Chest X-ray showed no abnormalities.Postoperatively, the mass spontaneously diminished to20 mm in size and the patient was well with tumour 8months after biopsy.

The submitted biopsy specimen measuring 20 mmwas elastic and soft with a brownish white cut-surfaceand haemorrhage. Microscopically, the tumour waswell-demarcated and encapsulated. The tumour con-sisted of a patternless proliferation of ovoid or spindlecells (Figure 1). The tumour cells had ovoid or fusiform,vesicular nuclei with inconspicuous nucleoli and scantto a moderate amount of indistinct cytoplasm. Multi-nucleated giant cells were scattered throughout thelesion. Some of them had a floret-like or syncytialappearance. Some multinucleated cells were located inthe perivascular areas but did not line vascular spaces(Figure 1). Intranuclear cytoplasmic inclusions wereoccasionally seen. Mitotic figures were rarely seen. Thestroma was fibrous, myxoid, or haemorrhagic and richin vascularity. Some areas showed a pericytomatous

vascular pattern. In the myxoid areas, there was aprominent network of small vessels with haemorrhage(Figure 1). Pseudovascular spaces lined by multi-nucleated giant cells were not observed. Small scatteredaggregates of lymphocytes, mast cells, and haemosiderin-laden macrophages were also present. Immunohisto-chemically, the tumour cells, including multinucleatedgiant cells, were diffusely and strongly positive forvimentin and CD34 (Figure 2). The tumour cells wereuniformly negative for S100 protein, cytokeratinCAM5.2, epithelial membrane antigen, Leu-7, desmin,HHF35, alpha smooth muscle actin, factor VIII-relatedantigen and CD31.

The current case is light microscopically similar togiant cell angiofibroma of the orbit1,2. The original casesare characterized by a richly vascularized, patternlessspindle-cell proliferation containing pseudovascularspaces. Multinucleate giant cells are scattered through-out lesion and line pseudovascular spaces1. This caseand the case reported by Ganesan et al.2 lacked

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Figure 1. a, Tumour is characterized by a patternless proliferation of ovoid or spindle cells and pericytomatous stromal vessels. Multinucleatedgiant cells are scattered throughout the lesion (H & E). b, In myxoid areas, there are a prominent network of small vessels and floret-like multi-nucleated giant cells (H & E).

pseudovascular spaces containing eosinophilic streakyor granular material. This feature was not clearlydefined by Dei Tos et al. The true nature of pseudo-vascular spaces remains unclear. This case wasclinically characterized by rapid swelling of the neck, awell-demarcated solid and cystic lesion, and a tendencyto spontaneously diminish after the biopsy. It mightrepresent massive stromal haemorrhage, degenerationand angiectatic change in the tumour.

The differential diagnoses include solitary fibroustumour, giant cell fibroblastoma and multinucleate cellangiohistiocytoma. The histology of this case over-lapped with that of these lesions. Solitary fibroustumour is well circumscribed and characterized by apatternless spindle cell proliferation, variable cellularity,

myxoid or hyalinized stroma, rich vascularity, and focalhaemangiopericytomatous pattern. However, multi-nucleated giant cells are not a recorded feature ofsolitary fibrous tumour of various sites3,4. Giant cellfibroblastoma has giant cells of floret type but hasinfiltrative margins, and occurs in early childhood5.Giant cell angiofibroma, solitary fibrous tumour, andgiant cell fibroblastoma are CD34 positive. Multinucle-ate cell angiohistiocytoma is a cutaneous disorder andoccurs in adult women as multiple, violaceous papulesthat usually involve the legs or hands6.

This neoplasm seems to behave in a benign fashionwith a potential for local recurrence if incompletelyresected1,2. Dei Tos et al.1 indicate that spindle cells ingiant cell angiofibroma are of fibroblastic nature. Thesefacts indicate that giant cell angiofibroma and solitaryfibrous tumour may be clinicopathologically closelyrelated although some of the former are poorlycircumscribed. There is a possibility that these lesionsmay be different phases in the evolution of the samecondition. This case indicates that giant cell fibroblast-oma can arise in extraorbital sites. This neoplasmshould be included in the differential diagnosis of softtissue spindle cell tumours with multinucleated giantcells.

M.FukunagaS.Ushigome

Department of Pathology,The Jikei University School of Medicine,

Tokyo, Japan

1. Dei Tos AP, Seregard S, Calonje E, Chan JKC, Fletcher CDM. Giantcell angiofibroma. A distinctive orbital tumor in adults. Am. J. Surg.Pathol. 1995; 19; 1286–1293.

2. Ganesan R, Hammond CJ, Van der Walt JD. Giant cell angiofibromaof the orbit. Histopathology 1997; 30; 93–96.

3. Goodlad JR, Fletcher CDM. Solitary fibrous tumour arising atunusual sites: analysis of a series. Histopathology 1991; 19; 515–522.

4. Suster S, Nascimento AG, Miettinen M, Sickel JZ, Moran CA.Solitary fibrous tumor of soft tissue. A clinicopathologic andimmunohistochemical study of 12 cases. Am. J. Surg. Pathol. 1995;19; 1257–1266.

5. Dymock RB, Allen PW, Stirling JW, Gilbert EF, Thornbery JM. Giantcell fibroblastoma. A distinctive, recurrent tumor of childhood. Am.J. Surg. Pathol. 1987; 11; 263–272.

6. Smith NP, Cerio R, Wilson Jones E. Multinucleate cell angiohistio-cytoma: an acquired vascular anomaly to be distinguished fromKaposi’s sarcoma. Br. J. Dermatol. 1990; 122; 651–653.

Correspondence 189


Figure 2. Diffuse and strong membrane staining of CD34(immunostaining).

multinodular pleural involvement in aggressive systemic mast cell disease

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