Low molecular weight cytokeratin in a spindle cell squamous carcinoma

CORRESPONDENCE Citrobacler was cultured from the urine. On further questioning the patient gave a history of owning both cats and dogs and1 of having been scratched several times by cats. Careful examination of the skin after the diagnosis of bacillary angiomatosis was made revealed no lesions.

irregular contour. Globular structures 01 variable probably representing fragmented and degenerated ria, were also noted (Fig 2, right).

PATHOLOGY

This report describes the unique occurrence of’ bacitlary angiomatosis presenting as a soft-tissue and lymph node mass with probable bone involvement but with no skin lesions. This unusual presentation combined with the histologic appearance of highly cellular vascular channels and a negative Steiner stain at first prompted a diagnosis of angiosarcoma. This diagnosis was revised when electron microscopy demonstrated bacteria which were similar to the cat scratch organism previously described.‘-” Of note is the fact that a few of the organisms demonstrated degenerative changes, probably due to antibiotic therapy (vancomycin and bactrim) which the patient received prior to the wide excision of his tumor. It would be interesting to see if’ in the future similar changes are found in patients whose lesions involute with antibiotic therapy. In retrospect, the foci of acute inflammation seen within the soft tissue vascular lesion herein reported. and previously described in skin lesions,‘,’ provide a clue to the true nature of’ this tumor which simulated a malignant vascular tumor. It is suggested that baciltary angiomatosis be considered in any HIV-seropositive patient presenting with soft-tissue vascular lesions, even in the absence of skin involvement.

DISCUSSION

The specimen consisted of a large portion of the Serratus anterior and Latissimus dorsi muscles. In between the two muscle bundles and firmly adherent to them was a 4 by 3.5 by S.!i cm firm, white mass containing several reddish nodules measuring from 0.5 to 2 cm in diameter. These nodules were scattered throughout the mass. Attached to it was a tag of adipose tissue and lymph nodes which was designated as axillary dissection. Microscopic examination revealed large areas of vascular tumor tissue within dense fibrous tissue. An occasional nodule of vascular tumor was found within skeletal muscle. In areas, the tumor showed well-formed vessels with fibrous tissue spaced evenly between them (Fig 1, left). Howrver, these often merged with areas of poorly formed vessels marked by cellular walls and indistinct lumens (Fig 1, I-ight). The poorly formed vessels predominated in the lymph nodes. The endothelial cells had vesicular nuclei and J)rominent nucleoli. Mitosis were rare and basophilic granular areas, were not seen in the interstitium. Within both patterns inflammatory cells, often in small-to-moderate sized clusters. were noted between vascular channels. Many of these inflammatory cells were neutrophils, often showing nuclear fragmentation. Scattered lymphocytes, plasma cells and histiocytes were also seen. Steiner stain performed in the initial sections was negative; however, a Warthin-Starry stain performed after the electron microscopic findings were known, showed clusters of small bacterial rods. Ultrastructural study performed on material obtained from the soft tissue mass and fixed in glutaraldehyde. demonstrated clusters of bacilli. They were located extracellularly, within the connective tissue surrounding blood vessels (Fig 2, left). The t~acilli measured approximately 2,000 nanometers in length by 500 nanometers in width. The bacteria had a trilaminar wall with two electron-dense layers separated by a less electron-dense Iaver.. In scjme rods the cytoplasm was separated from the wall by a uniform electron-lucent zone, and a well-defined plasma membrane was noted. The cytoplasm was coarsely granular with electron-dense areas. Several organisms were noted to have an indistinct, more finely granular and elect] on lucenl cytoplasm, to appear swollen, and to have an

.4ckno&dg?nr?~t. The authors thank J. Gre( a\ for technical ;Issistancr and Ct. I.erro toor typing the manuscripr. REFERENCES

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Low Molecular Weight Cylokeratin in a Spindle Cell Squamous Carcinoma

CORRESPONDENCE

Guidelines

sizes, bacte-

for Letters

Letters to the Editor will be published at the discretion ~jt. the editor as space permits and are subject to editing and abridgement. They should be Fypewritten, double-spaced, and submitted in triplicate. They should be limited to 500 words or less and to no more than five pertinent references.

1 569

To the E&or:-We would like to verify the findings and sentiments expressed by Kiernan and Mortimer.’ The application of cytokeratins of different molecular weights arose in the resolution of the problem of spindle cell squamous carcinoma versus carcinosarcoma. The obvious squamous carcinoma and dysplastic (full thickness) squamous epithetium stained strongly with high molecular weight cytokeratin. The spindle cell areas were negative. The in-built control of norlnal squamous lining was also positive. The tumor was then marked for low molecular weight cytokeratin (CAM 5.2). The squamous carcinoma areas and, im-

Volume 21, No. 5 (May1990)

HUMANPATHOLOGY

about the precise nature of CAM 5.2, and its expression by a squamous cell tumour may reflect the presence of a cytokeratin of 50 kd in some instances, which is approaching the higher molecular weight cytokeratin range. Thus, it is apparent that there is some truth in the recent series of disparate claims of immunocytochemical expression of CAM 5.2 in squamous cell carcinomas. The resolution of the controversy will depend on precise definition of the characteristics of particular antisera to which the attention of the relevant commercial agents is drawn.

portantly, the spindle cell component were positive. Interestingly, the preinvasive areas with full-thickness dysplasia were negative. CAM 5.2 was not found in the normal squamous epithelium either. Thus, the presence of CAM 5.2 helped to establish the diagnosis of a spindle cell carcinoma rather than a carcinosarcoma. The negativity of the full-thickness dysplastic areas correlates with the findings of Angus et al,’ in which a proportion of CIN III did not stain with CAM 5.2. RUNJAN CHETTY FFPATH DERYCK A. TAYLOR PHD University of Cape Town Medical Cape Town, South Africa

G. MORTIMER MRCPATH University College Hospital Galway, Ireland

School

1. Kiernan M, Mortimer G: Low molecular weight cytokeratin expression in squamous cell carcinomas. HUM PATHOL 20:92, 1989 (letter) 2. Angus B. Biberu S, Purvis J, et al: Cytokeratins in cervical dysplasia and neoplasia: A comparative study of immunohistochemical staining using monoclonal antibodies NCL-5D3. CAM 5.2 and PKKl. .I Pathol 155:71. 1988 The above letter was referred to the authors of the article in question, who offer the following reply: To the Editor:-The controversy concerning the expression of the low molecular weight cytokeratin CAM 5.2 by squamous cell carcinomas continues’.2 and is fueled by the recent letter from Drs Chetty and Taylor. These writers’ comments seem to support the views previously expressed by Dr Kiernan and myself. Some elaboration and modification of our views arises from further studies using monoclonal antibodies in combination, in relation to a variety of benign and malignant epithelial lesions. This work will be reported in some detail later, but some preliminary observations are pertinent at this point. Three anticytokeratin antibodies have been used in a panel in evaluating a variety of carcinomas. These include anticytokeratin CAM 5.2 (Becton Dickinson, Mountain View, CA), NCL5D3, and RCK102 (both Urodiagnostics, UK). Among the squamous carcinomas examined, differences in the expression of CAM 5.2 were noted depending on site of origin of tumors. Squamous carcinomas of urinary bladder and skin both expressed CAM 5.2 weakly, with stronger staining observed with NCL5D3 and RCK102 (particularly the latter). However, in the case of cervical, vocal cord, and esophageal tumors, there was no detectable CAM 5.2 or NCL5D3, although strong positivity was obtained with RCK102. Thus, the expression of individual cytokeratins may depend on the site of origin of particular squamous carcinomas in addition to tumor type, tissue fixation, and immunocytochemical methods.2.-’ Another variable that must be evaluated concerns the precise constitution of the anticytokeratin antibody CAM 5.2 itself. The manufacturer’s data sheet accompanying the CAM 5.2 used in our recent project described the antiserum specificity as human cytokeratin of 39 and 43 kd, which does not correlate with Mall’s catalog nos 8 and 18, as cited by the manufacturer.” These particular Mall’s catalog numbers correspond to molecular weights of 52.5 and 45 kd, respectively.” The anticytokeratin CAM 5.2 used by us previously carries different specificity under the same manufacturer’s literature, purporting to Identify cytokeratins of 39, 43, and 50 kd,3 supposedly corresponding to Moll’s catalog nos. 8, 18, and 19. In fact, Mall’s catalog no. 19 corresponds to human cytokeratin of molecular weight 40 kd.5 The latter characteristics correspond exactly with monoclonal cytokeratin NCL5D3, although our latest project showed that CAM 5.2 and NCL5D3 were not coexpressed in our cases. Thus, there is some genuine confusion

570

1. Kiernan M. Mortimer G: Low molecular weight cytokerati” expression in squamous cell carcinoma. HUM PATHOL 20:92. 1989 (letter) 2. Gown AM: Reply. HUM PAT~~~L 20:92, 1989 3. Immunocyto&e&try Systems. Mountain View, CA. Becton Dickinso” 4. Co&n DJ. Gown AM: Review of selected lineage-directed antibodies useful in routinely processed tissues. Arch Pathol Lab Med 113:645-652. 1989 5. Mall R. Franke WW, Schiler DL, et al: The catalog of human cytokeratins: Patterns of expression in normal epithelium, tumors. and cultured cells. Cell 31:11-24. 1982

Staining Patterns of Plasmacytoid Monocytes With Lectins To the Editor:-We read with interest the paper of Facchetti et al’ describing a close topographic and cytogenetic relationship between plasmacytoid monocytes (so-called plasmacytoid T cells [PTCs]) and epithelioid cells. Facchetti and coworkers confirmed and broadened our original observation, published in the January 1987 issue of Human Pathology,2 that PTCs are not only CD4 + , but also express antigens detected by the macrophage-specific monoclonal antibodies Ki-M6 and Ki-M7. Facchetti and colleagues also noted reactivity of PTCs with the lectin ConA, but did not describe the staining pattern in these cells. However, it is essential to state the cellular site of the lectin binding since macrophages show cytoplasmic staining with certain lectins that stain only the cell membrane in lymphocytes. 3.4 We recently studied the lectin binding profile of PTCs, macrophages, and lymphocytes histochemically with a panel of fluoresceinated lectins and found constant, strong cytoplasmic staining of PTCs and macrophages by ConA, PHA-L, PNA, WGA, RCA-I, and RCA-II.” In lymphocytes, however, staining by the same lectins was confined to the cell membrane. These findings provide further evidence of a close association between PTCs and the myelo-monocytic system. HEINZ-AUGST

II. Medizinische Kiel, FRG UDO

HORST, MD

Klinik der Universitit

SCHUMACHER, MD

Anatomische Anstalt Miinchen, FRG

der Universitgt

HANS-PETER HORNY, MD

Pathologisches Institut Tiibingen, FRG

der Universitgt

1. Facchetti F, De Wolf-Peeters C, De Vos R, et al: Plasmacytoid monocytes (so-called plasmacytoid T cells) in granulomatous lymphadenitis. HUM PATNOL.20:588-593, 1989 2. Horny H-P, Feller AC, Horst H-A. et al: Immunocytology of plasmacytoid T cells: Marker analysis indicates a unique phenotype of this enigmatic cell. HUM PATHOL 18:28-32, 1987