Correspondence

Pigmented squamous cell carcinoma of nasalcavity

Sir: Pigmented squamous cell carcinoma is an uncom-mon entity, previously described in the cornea andconjunctiva, and oral cavity.1–3 To our knowledge, thisis the first case of pigmented squamous cell carcinoma(PSCC) described in the nasal cavity.

A 64-year-old man presented with an ulcer in the leftnasal cavity, involving the vestibule and ala, andextending up to the columella. The patient also hadcervical lymphadenopathy. An initial incision biopsy ofthe lesion had been reported as malignant melanoma.Subsequently, the patient underwent wide excision ofthe ulcer with cervical lymph node dissection.

Grossly the wide excision specimen showed a blackishulcer 20 × 10 mm. Histologically the ulcer revealed awell differentiated squamous cell carcinoma withsquamous epithelial pearls. In extensive areas of thetumour, the carcinomatous squamous cells showedabundant brownish-black pigment granules within thecytoplasm (Figure 1). Interspersed were melanocytesand melanophages. Sections from the cervical lymphnodes showed metastatic squamous cell carcinoma withabundant pigment granules within the cytoplasm of theneoplastic cells (Figure 2). The pigment granules werenegative for iron by the Perls’ reaction and positive formelanin by the Masson–Fontana technique. Bleachingthe sections with 0.5% potassium permanganatesolution totally removed the pigment, thus confirmingthe nature of the pigment to be melanin. Immuno-histochemically the melanin containing neoplasticepithelial cells stained positive for cytokeratin andnegative for S100 protein. With the above findings a

diagnosis of pigmented squamous cell carcinoma withlymph node metastasis was made.

Although melanocyte colonization is well describedin association with many tumours including squamouscell carcinoma, breast carcinoma, anorectal adenocar-cinoma, etc.;4–6 true pigmented squamous cell carcin-oma is a rarity. Ultrastructural study performed in twoof the previously documented cases of PSCC demon-strated four distinct type of cells containing melaninpigment — neoplastic squamous cells, melanocytes,macrophages and Langerhans’ cells.1,2 The mechanismof melanin deposition in carcinomatous epithelial cellsis discussed by Jauregui and Klintworth.1 They postu-lated that the neoplastic epithelial cells obtainedmelanin granules from melanocytes in a mannersimilar to squamous cutaneous cells, i.e. by thephagocytosis of the tips of the melanosome filleddendrites of melanocytes and/or by the ingestion ofmelanin granules.

The clinical course of PSCC has not been well definedbecause of the small number of cases. However, theredoes not seem to be any relationship between the degreeof pigmentation and the degree of malignancy.1 In ourcase, the patient is well and free from recurrence 14months after surgical excision.

A MathewsE K Abraham

S AmmanM K Nair*

Departments of Pathology and *Radiotherapy and Oncology,Regional Cancer Centre, Trivandrum, Kerala, India

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Figure 1. Keratinized squamous carcinoma cells with abundantmelanin pigment within the cytoplasm (H & E, × 400).

Figure 2. Lymph node with metastatic pigmented squamous cellcarcinoma. Residual lymphoid tissue seen towards the left field(H & E, × 40).

1. Jauregui HO, Klintworth GK. Pigmented squamous cell carcinomaof cornea and conjunctiva — a light microscopic, histochemicaland ultrastructural study. Cancer 1976; 38; 778–788.

2. Kuwabara H, Uda H, Miyaguchi M et al. Pigmented squamous cellcarcinoma of the alveolar ridge in the oral mucosa. Oral Surg. OralMed. Oral Pathol. 1994; 77; 61–65.

3. Salisburg JA, Szpak CA, Klintworth GK. Pigmented squamous cellcarcinoma of the conjunctiva. Ophthalmology 1983; 90; 1477–1481.

4. Modica LA, Youngberg GA, Avila FO. Melanocyte colonization of anoral carcinoma. Histopathology 1990; 17; 477–478.

5. Azzopardi JG, Eusebi V. Melanocyte colonization and pigmentationof breast carcinoma. Histopathology 1977; 1; 21–30.

6. Chumas JC, Lorelle CA. Melanotic adenocarcinoma of theanorectum. Am. J. Surg. Pathol. 1981; 5; 711–717.

Primary extraskeletal osteosarcoma of thepenis with a malignant fibrous histiocytoma-like component

Sir: Extraskeletal osteosarcoma is a rare malignant softtissue tumour which primarily affects patients in thesixth and seventh decade.1,2 Its most common locationis in the extremities and the retroperitoneum while

the organs are a very rare primary site.1 To ourknowledge, only two cases of primary extraskeletalosteosarcoma of the penis have been describedpreviously.3,4

A 70-year-old man presented with a 2-month historyof a slowly growing penile nodule, nocturia and poorurine stream. Physical examination revealed an ulcer-ated tumour of the glans penis, approximately 20 mm indiameter. Partial penectomy was performed and furtherinvestigations showed no evidence of tumour spread. Nofurther therapy was given but 11 months later thepatient developed pulmonary metastases and dieddespite chemotherapy treatment.

A partial penectomy specimen measured65 × 35 × 30 mm and contained a rounded, firm, grey-ish-white tumour 22 mm in diameter with no obviouscapsule. Histologically, the tumour consisted of twointermingling components. The osteosarcoma-like com-ponent comprised broad islands of osteoid rimmed byseams of malignant-appearing plump osteoblasts andosteoclast-like giant cells; the osteoid contained osteo-blasts of the same malignant appearance (Figure 1a).

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Figure 1. a, An osteosarcomatous area with osteoclast-like giant cells. b, A malignant fibrous histiocytoma-like area of the tumour.

The malignant fibrous histiocytoma-like componentcomprised pleomorphic spindle-shaped cells and plumpcells arranged in fascicles with a storiform pattern(Figure 1b). Numerous bizarre and osteoclast-likemultinucleated giant cells and mitotic figures wereencountered. Mononuclear and bizarre multinucleatedgiant cells in both components of the tumour werestrongly and diffusely vimentin positive. Osteoclast-likegiant cells were vimentin negative, but they showedCD68 (KP-1) immunopositivity as did the scatteredmononuclear cells within the malignant fibrous histio-cytoma-like areas. Numerous mononuclear cells alsoexpressed CD68 positivity while CAM5.2 and HHF35(panactin) were negative.

Extraskeletal osteosarcoma accounts for about 1% ofall soft tissue sarcomas. The criteria for the diagnosis arethat the tumour is located in the soft tissues withoutattachment to bone or periosteum, has a uniformsarcomatous pattern (to exclude a mixed malignantmesenchymal tumour), and produces osteoid and/orcartilage matrix.1,2 There are reports with both maleand female predominance, but in all series average ageat presentation is much older than for the bonecounterpart (47.5 to 57 years).1,2 In this report, as inboth previously reported cases of extraskeletal osteo-sarcoma of the penis, the patients were even older — inthe eighth decade of life.3,4

Various histological patterns of extraskeletal osteo-sarcoma have been recognized including osteoblastic,fibroblastic, chondroblastic, giant cell, telangiectaticand small cell pattern.1,2 The giant cell type might bedifficult to distinguish from malignant fibrous histiocyt-oma of the giant cell type as giant cells with bizarrenuclei and osteoclast-like giant cells can be present inboth tumours.1,5 While some authors regard thepresence of small foci of osteoid or bone consistentwith the diagnosis of malignant fibrous histiocytomaothers classify them as extraskeletal osteosarcomas.5 Inour case, immunopositivity of the tumour with CD68confirmed the histiocytic origin of the osteoclast-likegiant cells. Diffuse vimentin and CD68 (KP-1) positivityand negative cytokeratin CAM5.2 was in agreementwith the mesenchymal differentiation of the tumour. Wethought it was appropriate to label this tumour asextraskeletal osteosarcoma because of large amount ofosteoid and evidence of osteoblastic differentiation. Thefinding of malignant fibrous histiocytoma-like areas inassociation with otherwise well-differentiated sarcomacan be explained as a morphological manifestation ofpoorly differentiated (de-differentiated) part of sarco-mas; yet, rare cases of malignant fibrous histiocytoma ofthe penis without any other specific line of differentia-tion have been reported too.6

Extraskeletal osteosarcoma and malignant fibroushistiocytoma also share many clinical features includ-ing the age at presentation, duration of the symptoms,clinical outcome and therapeutic implications1,6 whichsuggest closely related histogenesis and common originfrom primitive mesenchymal cells of both tumours.1

The overall prognosis is poor with 60–70% ofpatients dying of disease from 2 to 54 months afterthe diagnosis,1,2 Both local recurrences (45–50%) anddistant metastases (60–65%) are very common1,2 withthe lungs as the most common site of metastases(>80%). Metastases usually develop within 3 years afterthe diagnosis, indicating the aggressive course and fataloutcome of the disease.1,2 Although radical resectionsseem to be the best option for local control ofextraskeletal osteosarcoma,2 all three patients withthe penile tumour developed metastases and died within12 months after surgery.3,4

D BaceticM Knezevic*

Z StojsicM Atanackovic

G M Vujanic†

Institute of Pathology, Medical School, Belgrade,*Department of Pathology, Medical School, Kragujevac,

Yugoslavia, and †Department of Pathology,University of Wales College of Medicine, Cardiff, UK

1. Enzinger FM, Weiss SW. Soft Tissue Tumors, 3rd edn. Mosby: StLouis, 1995, 1026–1035.

2. Lee JSY, Fetsch JF, Wasdhal DA, Lee BP, Pritchard DJ, NascimentoAG. A review of 40 patients with extraskeletal osteosarcoma.Cancer 1995; 76; 2253–2259.

3. Edwards AT, Somerville JJF. Primary osteosarcoma of penis. Br. J.Urol. 1990; 66; 552–553.

4. Sacker AR, Oyama KK, Kessler S. Primary osteosarcoma of thepenis. Am. J. Dermatopathol. 1994; 16; 285–287.

5. Hollowood K, Fletcher CDM. Malignant fibrous histiocytoma:morphologic pattern or pathologic entity? Sem. Diagn. Pathol.1995; 12; 210–220.

6. Moran CA, Kaneko M. Malignant fibrous histiocytoma of the glanspenis. Am. J. Dermatopathol. 1990; 12; 182–190.

Hepatoid adenocarcinoma of the stomachwith extensive neuroendocrinedifferentiation and a coexisting carcinoidtumour

Sir: Hepatoid adenocarcinoma represents a rare, newlydescribed type of carcinoma which could be included inthe group of non-germ cell tumours of endodermalorigin with the ability to produce fetal proteins like

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alpha-fetoprotein (AFP). Strict criteria for the diagnosishave been established very recently,1 allowing thedescription of typical hepatoid tumours in the sto-mach,1–3 ovary, lung and other extremely rare localiza-tions including urinary bladder,4 pancreas, renal pelvisand papilla of Vater. In contrast to this distinct type ofadenocarcinomas, hepatoid differentiation is a relativelyfrequent component of germ cell tumours, especiallyyolk sac tumours.5 In the stomach, a typical hepatoidadenocarcinoma, apart from the hepatoid features,usually includes areas of adenocarcinoma of intestinaltype according to Lauren’s classification, while mildneuroendocrine differentiation has rarely beenreported.1 We present a case which is the first reportof hepatoid adenocarcinoma with extensive neuroendo-crine differentiation and a coexisting carcinoid tumourof the stomach.

A 48-year-old man presented with anaemia, remark-able weight loss and melana. Endoscopy revealed ahaemorrhagic ulcerative tumour of the body of thestomach consistent with an advanced gastric carcin-oma which was also detected by computed tomography(CT) of upper abdomen. In addition, whole body CT scanshowed enlargement of the regional lymph nodeswithout any other metastatic involvement. After thediagnosis was made, a total gastrectomy was performed.Pre-operative serum AFP levels were not determined.Postoperatively, blood tests revealed an elevated serumAFP level (800 ng/ml on postoperative day 25) whilecarcinoembryonic antigen (CEA), and other tumourmarkers were negative. The patient was placed onsystemic chemotherapy with doxorubicin, mitomycin-Cand 5-fluorouracil biologically modulated by folinicacid. Octreotide was also added for the treatment of theneuroendocrine tumour component. After four courses,AFP levels have declined to 50 ng/ml and remainedstable for two more months despite chemotherapy.Adjuvant radiation therapy was finally used for theelimination of minimal residual disease. One year afterthe surgery, patient remains well with no evidence of arecurrent tumour.

Gross pathological examination showed a wellcircumscribed excavated tumour 70 × 55 mm in size,located on the anterior wall of the gastric body. Thetumour was classified into Borrman III type. Micro-scopically, the predominant feature was large polygonalhepatocyte-like cells with abundant eosinophilic finegranular cytoplasm which formed solid sheets or werearranged in a trabecular pattern (Figure 1a). Solid andtubular structures of moderately and poorly differen-tiated adenocarcinoma of intestinal type were inter-mingled with hepatoid areas. The intestinal-typeadenocarcinoma cells presented mucus production

and occasionally clear cytoplasm. Intracytoplasmichyaline globules stained by PAS and resistant to diastasedigestion were observed in many adenocarcinoma andhepatoid cells. PTAH was negative. The tumourinfiltrated massively all layers of the gastric wall andinvasion of a large number of venules as well asoccasional bigger intravenous carcinomatous thrombiwere found. Metastatic disease was seen in most of theregional lymph nodes (12 out of 14), showing the samehistological features of the neoplasm. Interestingly, inone of the sections adjacent to the gastric tumour, nearits proximal boundary, a small incidental carcinoidtumour, 4 mm in maximum diameter, was found whichconfined in the mucosa and submucosal layer (Figure 2).No evidence of transition between carcinoid tumourand hepatoid carcinoma was observed. Moderatechronic gastritis with almost complete atrophy due tosevere intestinal metaplasia as well as ECL hyperplasia

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Figure 1. a, Solid sheets and trabecular arrangement of large polygo-nal ‘hepatoid’ cells with abundant eosinophilic cytoplasm and large,hyperchromatic, centrally located nuclei (haematoxylin and eosinstain, original magnification × 500). b, Immunohistochemistryrevealed a strong cytoplasmic expression of chromogranin whichwas detected in extensive areas of both, hepatoid and intestinal-typecell populations (DAB chromogen, haematoxylin counterstain,× 250).

was in the body of the stomach. Immunohistochemicalstains revealed that most of the hepatoid and a largenumber of intestinal-type cells were positively stainedfor AFP. Monoclonal CEA immunoreactivity was foundmostly in the latter cell population and in a smallnumber of hepatoid cells, while alpha-1-antitrypsin wasdetected predominantly in hepatoid areas and occa-sionally in intestinal-type cells. The most strikingimmunohistochemical finding was the intense positivityof extensive tumour areas for chromogranin whichstained a large number of hepatoid and intestinal-typeadenocarcinoma cells (Figure 1b).

The initial description2 of hepatoid adenocarcinomawas based on the morphological similarities withhepatocellular carcinoma as well as the detection ofincreased levels of AFP in the blood serum. Clinico-pathological studies of large series and further analysisof the biochemical nature of AFP,6 have strictly confinedthe diagnostic criteria only to the histologicallyrecognized hepatoid features, thus separating it fromthe wider group of AFP-producing gastric carcinomas.Hepatoid adenocarcinomas of the stomach seem to havea poorer prognosis than the other AFP producinggastric carcinomas, thus providing a prognostic sig-nificance in the histological classification suggested.1

More specifically, hepatoid tumours seem to be statisti-cally related with decreased %-year survival rate of thepatients and more frequent invasion of the veins1 with acharacteristic grossly visible intravenous proliferation.6

To our knowledge, the present case is the first report of atypical hepatoid adenocarcinoma with a coexistingcarcinoid tumour of the stomach. Emphasis is also

given to the presence of extensive neuroendocrinedifferentiation which has never been previouslydescribed, though chromogranin and NSE positivityhas been reported in a small number of AFP-producingneoplastic cells. Regarding histogenesis, contiguousnessof the embryonic stomach and liver originating from theforegut endoderm with elements of primary yolk sacduring the initial stages of the fetal development couldprovide a possible explanation of the origin of AFP-producing carcinomas. However, description of typicalhepatoid tumours in other very rare locations such asurinary bladder,4 is indicative of a multipotentialprimitive neoplastic cell with diverse differentiationcapacity. The development of both carcinoid tumoursand adenocarcinomas has been observed in chronicgastric mucosal diseases, ulcerative colitis and coeliacdisease. In this connection, the coexistence of hepatoidcarcinoma and carcinoid tumour may reflect differentphenotypic manfestations of the same neoplasticprocess. To determine the prognostic significance ofthe neuroendocrine component of hepatoid tumours, alarger number of similar cases as well as a long termfollow-up are required.

G Z RassidakisJ K Delladetsima

S P Letsos*A Polyzos†

A Yannopoulos*

Department of Pathology, *First Department of Surgery and†First Department of Propedeutic Medicine, University ofAthens Medical School, ‘Laiko’ General Hospital, Athens,

Greece

1. Nagai E, Ueyama T, Yao T, Tsuneyoshi M. Hepatoid adenocarci-noma of the stomach. A clinicopathologic and immunohistochem-ical analysis. Cancer 1993; 72; 1827–1835.

2. Ishikura H, Fukasawa Y, Ogasawara K, Natori T, Tsukada Y, AizawaM. An AFP-producing gastric carcinoma with features of hepaticdifferentiation: a case report. Cancer 1985; 56; 840–848.

3. Ishikura H, Kishimoto T, Andachi H, Kakuta Y, Yoshiki T.Gastrointestinal hepatoid adenocarcinoma: venous permeationand mimicry of hepatocellular carcinoma, a report of four cases.Histopathology 1997; 31; 47–54.

4. Sinard J, Macleay L, Melamed J. Hepatoid adenocarcinoma in theurinary bladder: Unusual localization of a newly recognizedtumour type. Cancer 1994; 73; 1919–1925.

5. Nakashima N, Fukatsu T, Nagashaka T, Sobue M, Takeuchi J. Thefrequency and histology of hepatic tissue in germ cell tumours. Am.J. Surg. Pathol. 1987; 11; 682–692.

6. Tsuchida Y, Fukui M, Sakaguchi H, Ishiguro T. Analysis of lectinaffinity immunoelectrophoretic profiles of serum alpha- fetoproteinfrom patients with yolk sac tumours and carcinoma of thegastrointenstinal tract: correlation with molecular structures.Tumour Biol. 1989; 10; 289–296.

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Figure 2. Small adjacent carcinoid tumour which is confined withinthe mucosa and submucosa layers (haematoxylin and eosin stain,original magnification × 30). Inset: Light microscopic appearance ofthe tumour included solid nests of small monotonous cells withoccasional acinar or rosette formation. Most of these cells werestrongly positive for chromogranin (haematoxylin and eosin stain,original magnification × 125).

Inverted papilloma-like transitional cellcarcinoma of the uterine cervix

Sir: Transitional cell carcinoma (TCC) is very rare in thefemale genital tract and only 10 cases of TCC of theuterine cervix have been previously described in theEnglish literature.1,2 A case of inverted papilloma-likeTCC of the uterine cervix is described with animmunohistochemical study.

A 23-year-old, prima-gravid woman was admitted tohospital because of threatened abortion at the 33rdweek of gestation. The patient had no significantprevious history. A soft, grey-white, polypoid nodule35 × 30 × 20 mm was noticed on the uterine cervix. Shedelivered uneventfully a healthy boy by Caesariansection at the 34th week and a biopsy of the top portionof the nodule was performed. Pelvic examination,computed tomography, and magnetic resonance ima-ging indicated an uterine cervical tumour extending tothe pelvic wall. Examination showed no significant

abnormalities. A biopsy of a basal portion of the nodulewas done. The patient was considered to be inoperable,and had a radiation therapy (50 Gy). The patient died ofextensive pelvic involvement by the tumour 12 monthsafter the diagnosis.

The first biopsy specimen, taken from the top portionof the nodule, showed an inverted papilloma-likeendophytic growth (Figure 1a). The lesion was char-acterized by glandular and solid proliferations ofurothelial cells (Figure 1b). The glands were lined byfive to 20 cell layers of transitional epithelium withoccasional. flattened surface cells. The tumour cells hadrelatively uniform round, oval, or spindle nuclei withvesicular chromatin and small nucleoli and a moderateamount of clear cytoplasm. The glands and solid nestshad smooth contours and occasionally had microcystformation. There was a transition between endocervicalglandular and the urothelial epithelium. Nucleargrooves were rarely observed. Nuclear atypia was mildand mitotic figures were six per 10 high-power fields

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Figure 1. a, Inverted papilloma-like endophytic growth with a smooth surface (H & E, × 40). b, Tumour is characterized by glandular and solidproliferations of urothelial cells with an occasional microcyst formation. Glands are lined by five to 20 cell layers of transitional epithelium.(H & E, × 100). c, Superficial layers of the tumourous urothelial epithelium are positive for CK20 (immunostaining, × 450).

(HPFs). The surface of the lesion was smooth andcovered chiefly by a single layer of endocervicalepithelium. No squamous cell element was observedand there was no evidence of stromal invasion in thesample. The stroma showed oedema and decidualizedstromal cells. The second biopsy specimen, which wastaken from the base of the lesion, showed virtually thesame proliferation patterns of the first biopsy specimen.However, the tumour demonstrated focally increasednuclear atypia, increased mitotic figures (70 mitoticfigures per 10 HPFs), stromal invasion, and localsquamous differentiation (less than 5% of the tumour)(Figure 2). Lymphatic invasion was observed. Thestroma showed a heavy lymphoplasmacytic infiltration.Immunohistochemicallly, many tumour cells werepositive for cytokeratin (CK) 7 (monoclonal, Dako) andsuperficial layers of the tumorous transitional epithe-lium were positive for CK20 (monoclonal, Dako)(Figure 1c).

The histology of the cervical tumour is virtuallyidentical to that of TCC, grade 1 or 2 of the urinarybladder. It showed an inverted papilloma-like patternand focal areas of squamous cell carcinoma. The firstbiopsy was too superficial to definitively assess invasion.The endophytic growth pattern may be explained by the

preferential involvement and expansion of endocervicalglands by the tumour. My purpose in presenting thiscase is chiefly to recognize papilloma-like TCC of theuterine cervix and to bring forward the problemsassociated with assessment of invasion. The glandular,nesting, and microcystic patterns in the presentneoplasm may be deceptively bland and mimic benignconditions and this type of lesion is prone to beunderdiagnosed. In these circumstances, biopsy fromthe base of the lesions or cervical cornization isrequired.

The main differential diagnosis includes invertedpapilloma and papillary squamous cell carcinoma.Inverted papilloma is characterized by anastomosingcord and trabeculae of urothelial cells with minimalnuclear atypia and rare mitotic figures, dome-shapedoverlying surface, and the lack of stromal invasion.1

This tumour differs from inverted papilloma in thepresence of mitotic figures and nuclear atypia and theabsence of peripheral palisading.3 The second biopsyshowed the apparent stromal invasion with focalsquamous differentiation. Papillary squamous cellcarcinomas show a prominent papillary configuration,keratinization, nuclear atypia and mitotic activity inboth non-invasive and invasive components.

Three cases of TCC1 and seven of papillary TCC2 of theuterine cervix have been recently reported. However,the current tumour differed in that the tumour had asmooth rather than papillary surface and a prominentglandular involvement and lacked fibrovascular corescovered by neoplastic epithelial cells. This tumourbehaved very aggressively and the patient died of theextensive pelvic invasion.

The profiles of CK7þþ/20þ in the tumour were thesame as those of TCC of the urinary bladder,2,4

indicating urothelial rather than Mullerian differentia-tion. The superficial CK20 staining of the epithelium isvery characteristic to TCCs of the urinary bladder.4 Allfour cases of the cervical TCCs reported by Koening etal.2 were CK7þ/20–. Endometrial TCCs were CK7þ or–/20–5 and transitional cell proliferation of the ovaryexcept in few cases were CK7þ/20–.4

Benign transitional metaplasia and transitional cellneoplasms of the uterine cervix have only recently beendescribed,1,6 and appear closely related.1 However,transitional metaplasia, which is usually seen inpostmenopausal women, was not discerned in thepresent case. Close embryologic relationship betweenMullerian type and urothelial epithelium is assumed.

M Fukunaga

The Department of Pathology, The Jikei University School ofMedicine, Tokyo, Japan

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Figure 2. Base of tumour demonstrates squamous differentiationwith increased nuclear atypia, increased mitotic figures, and stromalinvasion (bottom) (H & E, × 200).

1. Albores-Saavedra J, Young RH. Transitional cell neoplasms(carcinomas and inverted papillomas) of the uterine cervix. Areport of five cases. Am. J. Surg. Pathol. 1995; 19; 1138–1145.

2. Koening C, Turnicky RP, Kankam CF, Tavassoli FA. Papillarysquamotransitional cell carcinoma of the cervix: a report of 32cases. Am. J. Surg. Pathol. 1997; 21; 915–921.

3. Amin MB, Gomez JA, Young RH. Urothelial transitional cellcarcinoma with endophytic growth patterns. A discussion ofpatterns of invasion and problem associated with assessment ofinvasion in 18 cases. Am. J. Surg. Pathol. 1997; 21; 1057–1068.

4. Soslow RA, Rouse RV, Hendrickson MR, Silva EG, Longacre TA.Transitional cell neoplasms of the ovary and urinary bladder: acomparative immunohistochemical analysis. Int. J. Gynecol. Pathol.1996; 15; 257–265.

5. Liningwer RA, Ashfaq R, Albores-Saavedra J, Tavassoli FA.Transitional cell carcinoma of the endometrium and endometrioidcarcinoma with transitional cell differentiation. Cancer 1997; 79;1933–1943.

6. Egan AJM, Russell P. Transitional (urothelial) cell metaplasia of theuterine cervix: morphological assessment of 31 cases. Int. J.Gynecol. Pathol. 1997; 16; 89–98.

Malignant fibrous histiocytoma in a child’shand

Sir: Malignant neoplasia of the hand is exceptional inchildhood, and malignant fibrous histiocytoma (MFH) isextremely rare.1 We present a case of MFH in thesubcutaneous and soft tissue of the web space betweenthe first and the second metacarpal bone in a 6-year-oldboy.

The patient had a 18-month history of a tumour inhis left hand. The mass was seen initially with a slowlygrowing lesion as a erythematous papule but it wasrapidly progressive about 3 months before this admis-sion. Physical examination showed a small egg-sizedmovable tender mass. Radiographs revealed a45 × 45 mm soft tissue mass with cortical destruction

of the second metacarpal bone (Figure 1). His medicaland family histories were otherwise unremarkable. Themass was completely excised with an impression ofvascular neoplasm. The first dorsal interosseous musclewas nearly absent by atrophy due to tumour infiltration.The mass was relatively well circumscribed but withlocal periosteal extension. The gross pathological speci-men consisted of a relatively well circumscribed ovalmass devoid of overlying skin, measuring 55 × 45 mm.The cut surface showed whitish yellow tumour withwhitish intersecting streaks and haemorrhagic foci.Histologically, the tumour was extending to the musclefasciculi, muscle and periosteum with infiltrativemargins. It had a variable morphological pattern andshowed transitions from storiform areas to fascicular orpleomorphic patterns. The tumour consisted of plumpspindle cells arranged in short fascicles in a storiformpattern around slitlike vessels, and some polygonalcells, multinucleated giant cells and foamy histiocyteswith haemosiderin pigment. The spindle cells were welldifferentiated and resembled fibroblasts. Numeroustypical and atypical mitotic figures, lymphocytic infil-tration and collagen lay down in the stroma wereobserved. The tumour cells showed nuclear pleomorph-ism and hyperchromatism, irregular nuclear contourand frequent nucleoli (Figure 2). Immunohistochemi-cally, positivity for alpha-1-antitrypsin, lysozyme, CD68and vimentin, and negativity for S100 protein, desminand myoglobin were noted in the tumour cells. Electronmicroscopically, three major cell types were identified.The first cell type consisted of fibroblastic cells whichwere not lined with a basal lamina and had elongatednuclei, prominent nucleoli, free ribosomes, bands ofintracytoplasmic filaments and abundant lamellae ofrough endoplasmic reticulum. Collagen fibres were seenin the vicinity of these cells. The second cell typeconsisted of myofibroblastic cells which manifestednuclear clefting and contained wispy actin-like fila-ments beneath the cytoplasmic membrane. The thirdcell type consisted of histiocytic cells which containedoval or lobated nuclei, many cytoplasmic processes,numerous lysosomes, phagosomes and lipid droplets,and that were not joined to neighbouring cells andlacked basal lamina. Primitive mesenchymal cellshaving a narrow rim of cytoplasm largely devoid oforganelles except for free ribosomes and multinucleatedgiant cells were present in small numbers. Neitherlipoblast nor Z-band material were present in any foci.The final diagnosis was MFH, storiform-pleomorphictype. Four months after the operation there wascomplete remodeling of the second metacarpal bone.

Soft tissue sarcomas constitute the major form ofmalignant mesenchymal tumours in childhood. Of them,

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Figure 1. MRI view of the left hand reveals 45 × 45 mm sized softtissue mass with cortical destruction of the second metacarpal bone.

rhabdomyosarcoma is the most frequent variety. Theyare unusual in persons over 21 years of age.1 Bycontrast, MFH is a type of soft tissue sarcoma seen mostfrequent in older adults, and it occurs most frequently inan extremity or in the retroperitoneum, and pelvis.2,3 AMFH in the hand is exceptional, since only two werereported in a review of 200 cases of MFH occurred in allpopulation.2 In children, the most common sarcomas ofthe upper extremities are fibrosarcomas, and theseneoplasms develop mainly on the arms and forearmsand, less commonly, on the hands and fingers.4

According to the report of Corporon et al.,5 among the44 cases of MM in children three cases developed in apreviously irradiated field and only three cases hadhistologically confirmed nodal metastases and largetumour size (diameter >50 mm) was predictive of apoorer prognosis. Patients underwent pre- or post-operative radiotherapy with or without adjuvantchemotherapy, 89% of the cases had a completeresponse to therapy and the remainder had local relapseor pulmonary metastases.5 Tracy et al.6 described thatMFH in children may have a better prognosis than inadults.

Our patient, who underwent total removal of the

mass without additional radiotherapy or chemotherapyhas no sign of local recurrence or distant metastasis for12 months.

S-C LimD-C Kim

Y-K JeongC-H Suh

Department of Pathology, Chosun University College ofMedicine, Kwangju, South Korea

1. Raney RB Jr, Allen A, O’Neill J, Handler SD, Uri A, Littman P.Malignant fibrous histiocytoma of soft tissue in childhood. Cancer1986; 57; 2198–2201.

2. Weiss SW, Enzinger FM. Malignant fibrous histiocytoma: ananalysis of 200 cases. Cancer 1978; 41; 2250–2266.

3. Kearney MM, Soule EH, Ivins JC. Malignant fibrous histiocytoma: aretrospective study of 167 cases. Cancer 1980; 45; 167–178.

4. Owens JC, Shiu MH, Smith R, Hadju SI. Soft tissue sarcomas of thehand and foot. Cancer 1985; 55; 2010–2018.

5. Corporon CA, Black CT, Raney RB, Pollock RE, Lally KP, AndrassyRJ. Malignant fibrous histiocytoma in children. J. Pediatr. Surg.1996; 31; 1080–1083.

6. Tracy T Jr, Neifeld JP, DeMay RM, Salzberg AM. Malignant fibroushistiocytomas in children. J. Pediatr. Surg. 1984; 19; 81–83.

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Figure 2. A, Malignant fibrous histiocytoma showing a distinct storiform pattern. B, Malignant fibrous histiocytoma showing a more pleo-morphic area consisting of sheets of bizarre hyperchromatic nuclei and giant cells.

Paratesticular composite tumour ofepididymal-like and mucinous cells of lowmalignant potential

Sir: Both benign and malignant mucinous tumours ofthe epididymis and testis are rare.1 Because mucinoustumours of the testis are histologically similar to those ofovary, it has been proposed that they arise frommesothelium or Mullerian duct remnants. We report acase of a mucinous tumour consisting of mucinous,epididymal-like and neuroendocrine cells, and probablydeveloping from the epididymis or rete testis epithelium.

A 42-year-old white man presented to a urologistwith a history of pain and swelling of the right testis 10months after a vasectomy. Physical examination andsonography revealed an enlargement of the rightepididymis and testis. The remaining physical examina-tion was unremarkable. The patient underwent rightorchidectomy and has remained free of disease for 18months after the operation. The resected specimencontained a poorly circumscribed, soft, brownish lesion40 × 28 × 20 mm involving approximately one-third ofthe epididymis and one-third of the testis. Multiple cystscontaining thick brown mucinous material occupied50% of the mass. Microscopically, the lesion displayedfeatures of a mucinous tumour of intestinal type of lowmalignant potential by using criteria for ovarianmucinous tumours.2 It comprised lakes of mucin,without epithelial cells, with lakes of mucin dissectinginto the surrounding epididymis and testis. In addition,there were small and large cysts lined by columnarmucinous cells and scattered goblet cells, hyperplasticand mildly dysplastic mucinous epithelium(Figure 1a,b). In some areas, small acini and cystswere lined by ciliated and non-ciliated epitheliumresembling epididymal-like epithelium or a epitheliumwith a mixture of single or groups of epididymal-likecells and mucinous cells. These epididymal-like cellslacked mucinous cytology and contained numerousyellow to brown granules 50 mm in diameter (Figure2a,b). In a focal area, the epididymal-like epitheliumwere seen in continuity with the rete testis epithelium.Papillary structures of serous type, components ofteratoma and intratubular germ cell neoplasia werenot seen.

The granules in the epididymal-like cells were positivewith periodic–acid Schiff reaction with or withoutdiastase digestion (PAS-D) but not with Alcian bluestaining. The ciliated and non-ciliated epididymal-likecells without granules were negative with PAS-D andAlcian blue. The mucin stains (PAS-D and Alcian blue)were positive in mucinous epithelium and were focallyidentified in small acini of epididymal-like cells and in

the focal area of rete testis epithelium adjacent to groupsof epididymal-like cells. Where the epithelia had bothmucinous cells and epididymal-like cells with granules,there were cells showing focal positive staining in blueand violet for mucin with Alcian blue and combinedAlcian blue–PAS respectively in the apical portion of thecytoplasm, and focal positive staining in red with PAS-Din granules in the lower portion of the cytoplasm.Staining for neurone specific enolase (NSE) (Dako;dilution 1:100) and chromogranin A (CgA) (BoehringerMannheim; dilution 1:1000) revealed a few singleimmunoreactive cells in the basal portion of theepithelium. There were no NSE or CgA and immuno-reactive cells in the uninvolved testis or epididymis.

It is likely that the different cell types in the lesionwith clusters of epididymal-like cells developed as a

Correspondence 193

q 1998 Blackwell Science Ltd, Histopathology, 33, 184–194.

Figure 1. Mucinous component of the lesion composed of mucinousepithelium with focal goblet cell metaplasia (a) and an area withfeatures of mucinous tumour of low grade epithelial dysplasia (b).

result of differentiation from multipotential cells of theepididymal epithelium rather represented the entrappedepididymal cells within the lesion. These granules havethe colour similar to those in the normal epididymalcells (efferent tubules) and rete testis cells,3–5 anddifferent from Paneth cells that are bright-red. The

uniform size of these granules was probably related tothe hyperplastic or neoplastic nature of the cells. Thisidentification of the origin of the epididymal-like cellsfrom the epididymal epithelium almost excludes thepossibility of a metastatic mucinous adenocarcinoma.Furthermore, the absence of the ectodermal and othermesodermal derivatives makes it unlikely that the lesionrepresents an endodermal component of a teratoma.

In view of the focal changes in the rete testis, it islikely that this lesion arose from the epithelium of therete testis; however an origin from the efferent ductulesof the epididymis can not be excluded. In the embryo,epididymal tubules derive from Wolffian duct, and retetestis has the same origin with epididymis or testis. BothWolffian duct and testis arise from the coelomicepithelium. The potential of epithelium of the epididy-mis and rete testis to differentiate into mucinous cellshas not been proposed previously. However, thispotential of differentiation of Wolffian duct-derivedepithelium is probably similar to that of Mullerianduct derived epithelium, because they are of coelomicorigin.

K T MaiM Carlier*

C Lajeunesse†

Division of Anatomical Pathology, Department ofLaboratory Medicine, Ottawa Civic Hospital and

Department of Pathology and Laboratory Medicine,University of Ottawa, *Department of Pathology,

Montfort Hospital, and †Department of Surgery (Urology),Montfort Hospital, Ottawa, Ontario, Canada

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2. Zaloudek C. Ovarian neoplasms. In: Gompel C, Silverberg SG, eds.Pathology in Gynecology and Obstetrics. Philadelphia: LippincottCompany, 1994; 330–349.

3. Mai KT. Cytoplasmic eosinophilic granular change of the ductuliefferentes. J. Urol. Pathol. 1994; 2; 273–278.

4. Saitoh K, Terada T, Hatakeyama S. A morphological study of theefferent ducts of the human epididymis. Int. J. Androl. 1990; 13;396–376.

5. Goyal HO, Williams CS. The ductuli efferentes of the goat: amorphological study of ciliated cells. Anat. Rec. 1988; 220; 58–67.

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q 1998 Blackwell Science Ltd, Histopathology, 33, 184–194.

Figure 2. a, Focus of mixture of epididymal-like-cells (arrow) andmucinous cells (arrowhead). b, A high magnification of epididymal-like cells with yellow to brown granules (thick arrow), andmucinous cells (arrowhead) and mucinous cells containing yellowto brown granules (thin arrow).