Cytologic features of primary, recurrent, and metastatic dermatofibrosarcoma protuberans
Article first published online: 15 AUG 2002
Copyright © 2002 American Cancer Society
Volume 96, Issue 6, pages 351–361, 25 December 2002
How to Cite
Domanski, H. A. and Gustafson, P. (2002), Cytologic features of primary, recurrent, and metastatic dermatofibrosarcoma protuberans. Cancer, 96: 351–361. doi: 10.1002/cncr.10760
- Issue published online: 11 DEC 2002
- Article first published online: 15 AUG 2002
- Manuscript Accepted: 29 MAY 2002
- Manuscript Revised: 20 MAY 2002
- Manuscript Received: 5 MAR 2002
- Anna Lisa and Sven-Eric Lundgrens Foundation for Medical Research
- dermatofibrosarcoma protuberans;
- spindle cell sarcoma;
- fine-needle aspiration;
- fibrohistiocytic lesions;
Dermatofibrosarcoma protuberans (DFSP) is a low-grade spindle cell neoplasm involving both dermis and subcutis. Its diagnosis may be difficult to render from cytologic smears, as it shares some features with other spindle cell lesions occurring in the skin and soft tissue.
Fourteen aspiration smears from 12 patients with primary, recurrent, or metastatic DFSP, examined by fine-needle aspiration biopsy (FNAB), were reviewed and compared with corresponding surgical specimens (13 aspirates) and clinical data (one aspirate). The cytologic features of DFSP were evaluated. Other spindle cell lesions in the differential diagnoses were discussed.
Unequivocal spindle cell sarcoma diagnoses were rendered in nine aspirates, six of which were labeled correctly as DFSP in the original reports. In three aspirates, the preoperative diagnoses were inconclusive with regard to whether the tumors were benign or malignant. Two aspirates were diagnosed erroneously as benign spindle cell lesions. Cytologic features included tight clusters of bland spindle cells embedded in a collagenous/fibrillar and, often, metachromatic matrix along with dissociated, uniform, or slightly atypical spindle cells or bare nuclei. Tissue fragments showing a storiform pattern and entrapped fat tissue, reported in previous series, were less characteristic, presenting in nine and seven aspirates, respectively.
Correct subtyping of DFSP in fine-needle aspiration smears can be difficult, due to its morphologic overlapping with other spindle cell lesions. A combination of cytology with ancillary studies and appropriate clinical information is crucial to establishing a correct diagnosis. Cancer (Cancer Cytopathol) 2002. © 2002 American Cancer Society.
Fine-needle aspiration biopsy (FNAB) is the most common method used to diagnose epithelial neoplasms. The procedure has not been generally accepted in patients suspected of having bone or soft tissue neoplasms, however, despite numerous publications documenting the diagnostic accuracy and advantages of FNAB.1–8 The evaluation of spindle cell lesions probably represents the greatest challenge in aspiration cytology of soft tissue and skin9 and there are no cytologic criteria by which to define these tumors.
Dermatofibrosarcoma protuberans (DFSP) is a low-grade spindle cell neoplasm that most frequently affects the dermis and subcutis. This rare, fibrohistiocytic tumor tends to recur locally but has no metastatic potential. However, similar to some other sarcomas, recurrent and primary DFSP can progress to fibrosarcomatous (high-grade) DFSP, which can metastasize and be fatal to the patient.10 Although many studies have addressed histopathology, only one series11 and a few case reports12–14 have described the cytologic features of this relatively rare neoplasm. In addition, two series of FNAB of skin lesions mention DFSP.15, 16 The aim of the current study was to determine which cytologic features permit a confident diagnosis of DFSP in fine-needle aspiration (FNA) smears. Another objective was to compare FNA findings of DFSP with its fibrosarcomatous (high-grade) counterpart and with other spindle cell lesions which are differential diagnoses of DFSP.
MATERIALS AND METHODS
Fourteen aspiration biopsies performed as diagnostic procedures on 12 patients with primary, recurrent, and metastatic DFSP were retrieved from the files of the Department of Pathology and Cytology, Lund University Hospital, Lund, Sweden (13 aspirates) and the Department of Pathology and Cytology, Central Hospital, Kristianstad, Sweden (1 aspirate). For the procedure, 22–24-gauge needles attached to a disposable plastic syringe in a Cameco (Täby, Sweden) syringe holder were used. Aspirates were both air-dried (all 14 cases) and wet-fixed in 95% ethanol (11 cases). May-Grünwald-Giemsa (MGG) and hematoxylin and eosin stains, respectively, were applied. In one case, aspiration smears were fixed in 95% ethanol for immunocytochemistry; S-100, epithelial membrane antigen (EMA), CD99, and CD34 antibodies were used. The cytologic findings were evaluated and correlated to the histopathologic findings of excised tumors.
The patients comprised five women and seven men ranging in age from 27 to 73 years. Four patients presented with no history of any soft tissue neoplasm, two presented with recurrence of DFSP, and one with metastases of previously excised DFSP. The remaining five patients had a history of soft tissue or skin tumors, which had been diagnosed erroneously by histology as benign tumors (spindle cell lipomas [SCL], extra-abdominal desmoids, fibrolipomas), sarcomas (neurofibrosarcomas, spindle cell sarcomas), or as malignant tumors not otherwise specified (NOS). The tumors were located in the dermal and subcutaneous regions of the upper arm (three patients), shoulder (three patients), parotid area (two patients), chest (one patient), and groin (one patient). One patient with a history of fibrosarcomatous DFSP presented with multiple lung metastases and another patient presented with a deep located mass, showing no connection to the dermis.
Nine aspirates were evaluated originally as spindle cell sarcoma, six of which were diagnosed correctly as DFSP. Three additional aspirates were diagnosed as spindle cell tumors, but were not believed to be definitely malignant and two aspirates were diagnosed erroneously as benign spindle cell lesions. The follow-up period ranged from 10 months to 19 years. Clinical data and primary cytologic diagnoses are summarized in Table 1.
|No.||Gender||Age (yrs)||Size (cm)||Location||Clinical information||Original FNA diagnosis|
|1||Male||41||2.0||Upper arm||History of fibrolipoma in the upper arm, excised 1960. Admitted due to recurrence||Spindle cell sarcoma, most likely DFSP|
|2A||Female||72||2.0||Upper arm||History of DFSP in the upper arm, excised 1971. First recurrence 1981||Recurrent DFSP|
|2B||1.0||Upper arm||Second recurrence 1983||Recurrent DFSP|
|3||Male||61||2.5||Shoulder||Recurrence of malignant tumor in the shoulder, 12 yrs after primary surgery||Low-grade spindle cell sarcoma|
|4||Male||43||1.5||Parotid area||2-mo history of slowgrowing subcutaneous tumor||Suspicious for parotid tumor|
|5||Male||54||2.5||Groin||Recurrence of neurofibrosarcoma 1 yr after primary surgery||Spindle cell sarcoma|
|6A||Female||57||3.5||Upper arm||Subcutaneous tumor suspected to be fibromatosis; after first recurrence, the diagnosis changed to spindle cell lipoma||Fibromatosis|
|6B||2.5||Upper arm||Second recurrence of subcutaneous tumor termed for spindle cell lipoma||Low-grade or benign spindle cell tumor|
|7||Female||54||1.5 and 1.0||Shoulder||Second recurrence of DFSP, first presenting 4 yrs earlier||Recurrent DFSP|
|8a||Male||51||3.0||Lower arm||Slowgrowing, deep-seated tumor||Spindle cell sarcoma, DFSP vs. synovial sarcoma vs. MPNST|
|9||Female||54||3.0||Chest||Hard subcutaneous mass for 20 yrs, ectopic breast tissue?||Benign spindle cell lesion of uncertain type|
|10a||Male||32||0.5||Shoulder||Suspected recurrence of spindle cell sarcoma. Skin ulcer adjacent to skin transplantation||Recurrent DFSP|
|11||Male||27||1.5||Parotid area||Subcutaneous mass adherent to overlying skin of 4 mo duration. Atheroma? Parotid tumor?||Spindle cell tumor, inconclusive whether benign or malignant|
|12a||Female||46||Bilateral lung metastasis||History of DFSP in the abdominal wall, fist presenting 3 yrs earlier with two recurrences before metastasizing||Lung metastasis of DFSP|
The cytologic findings are summarized in Table 2. Seven aspirates were of high, three of moderate, and four of poor cellularity. All 14 aspirates were characterized by compact, often three-dimensional clusters (in 10 cases) of spindle cells with poorly defined cytoplasmic borders and relatively uniform, spindle-shaped, or oval nuclei usually with finely dispersed chromatin (Fig. 1A). In eight smears, these cells were embedded in a collagen matrix that showed, focally, a fibrillary pattern. In seven smears, this matrix showed myxoid changes with metachromasia in MGG-stained smears (Fig. 1B). In all 14 smears, small sheets of spindle cells as well as numerous dissociated cells or naked nuclei were also observed (Fig. 1C). In most of the smears, the proportion of cell clusters and dissociated cells was approximately equal. The spindle cells had a moderate amount of pale and poorly defined cytoplasm. Some of the spindle cells showed a little better defined cytoplasm with bipolar cytoplasmic processes (Fig. 2), but the majority of them had poorly preserved cytoplasm or lacked cytoplasm completely. The nuclei of the spindle cells were basophilic and fusiform, ovoid, or round, showing mild anisokaryosis and occasional irregular borders (Fig. 3A). Nuclear “grooves” and frequent (11 smears) inconspicuous nucleoli were seen (Fig. 3B). Somewhat coarser chromatin was occasionally seen in 6 smears (Fig. 3C) and mild pleomorphism in 10 smears (Figs. 1C, 2, 3A,B). It is important to point out, however, that the morphologic signs of nuclear pleomorphism were not associated only with the fibrosarcomatous variety of DFSP, because mild nuclear pleomorphism occurred in two of three smears of fibrosarcomatous DFSP and in eight smears of typical DFSP. Except in one case, no mitotic activity was seen in any of the smears. A storiform pattern was observed in cell clusters and sheets in nine smears (Fig. 4A), whereas the cellular arrangement was more or less irregular or slightly fascicular in five smears. In the patient who presented with lung metastases of fibrosarcomatous DFSP (Patient 12), the FNA smears of metastatic tumor were cellular, showing predominantly three-dimensional cell clusters with a prominent storiform pattern and scattered mild pleomorphism (Fig. 4B). In addition, scattered mast cells were found in two smears.
|No.||Cellularity||Cells||Nucleus||Stroma||Storiform pattern||Fat tissue|
|Clusters||Dissociated cells||Naked nuclei||Pleomorphism||Coarse chromatin||Mitoses||Nucleoli||Collagen matrix||Fibrillar matrix||Metachromasic matrix|
In summary, the most frequent type of smear was cellular with compact spindle cell clusters embedded in a collagen/fibrillar and/or myxoid matrix admixed with dissociated spindle cells or naked nuclei. Examination of FNA smears alone was not sufficient to differentiate DFSP from its high-grade, fibrosarcomatous counterpart.
Histologic specimens for 13 of the cases were available for review. All histologic slides showed the classic features of DFSP with a storiform pattern and bland or slightly pleomorphic spindle cells infiltrating subcutaneous fat. In Patient 8, the tumor location was atypical, involving deep subcutaneous tissue and muscle fascia but showing no connection with the overlying dermis (Fig. 5A,B). The histology of Patient 8 was similar to that of Patient 10, showing areas of increased cellularity, a loose storiform pattern, and a focal histologic appearance of fibrosarcoma. In such areas, increased mitotic activity (Fig. 5C) and decreased immunoreactivity for CD34 were noted. Again, it is important to point out that no particular cytologic features that could predict the presence of fibrosarcomatous areas were identified in FNA smears.
It is well known among cytopathologists who work with FNA that the interpretation of spindle cell lesions is difficult.9 As radical surgery is the treatment of choice in most cases of spindle cell sarcomas, distinguishing benign pseudosarcomatous proliferations and benign spindle cell tumors from malignant spindle cell tumors is often sufficient for the management of these lesions. Knowledge of the histologic subtype, however, is often necessary to establish whether a lesion is malignant or benign and to determine the grade of malignancy. The subclassification of low-grade malignant or benign spindle cell lesions, which often share morphologic, immunohistochemical, and clinical characteristics, can be quite challenging both histologically and in FNA smears.
In the current study, a known history of DFSP had a great influence on the correct cytologic diagnosis of the examined smears. In the four patients with a history of DFSP, all smears were interpreted correctly. However, in five patients without this clinical information, only two aspirates were labeled primarily as spindle cell sarcoma, with a suspicion of being DFSP. Of the remaining three patients, one aspirate was labeled as a spindle cell lesion, uncertain as to whether it was benign or malignant, one as a benign spindle cell lesion of uncertain type, and one was suspected to be a parotid tumor, NOS. Two patients presented with tumor recurrence, which had been diagnosed erroneously as a “neurofibrosarcoma” and sarcoma NOS, respectively. In these two cases, the smears were interpreted primarily as being spindle cell sarcoma and low-grade spindle cell sarcoma, respectively, without any further subtyping. The cytologic smears from Patient 10 who had a history of spindle cell sarcoma NOS were strongly suspicious for DFSP. The previously excised tumor was reviewed and the diagnosis changed to DFSP.
The differential diagnoses for DFSP include a spectrum of benign or low-grade malignant spindle cell lesions such as SCL, nodular fasciitis (NF), fibrous histiocytoma (FH), solitary fibrous tumor (SFT), neurilemoma, neurofibroma, desmoid-fibromatosis, and low-grade fibrosarcoma (Table 3). Some high-grade tumors such as synovial sarcoma or spindle cell melanoma (SCM) may occasionally show micromorphology similar to DFSP.
|Diagnosis||Clinical features||Cytologic features|
|Neurilemoma||Tumor of adults with variable location and size (often larger than 5.0 cm). Painful on aspiration. Often long history.||Variable yield. Mainly fascicles of spindled cells with moderate nuclear pleomorphism. Elongated nuclei with pointed ends, occasionally “fish-hook” and small, round nuclei. Fibrillar background, occasionally Verocay bodies.|
|NF||Usually superficial and smaller than 3.0 cm. Rapidly growing, painful, or tender mass often in the upper extremities of young adults. Most cases of NF regress spontaneously.||Cellular yield. Moderate to markedly pleomorphic spindled, triangular, or round cells. Nuclei have bland chromatin but often prominent nucleoli and occasional mitoses. Myxoid background and ganglion-like cells frequently present. Occasionally multinucleated and inflammatory cells. Late fasciitis often shows more uniform spindled cells than fasciitis in the growth phase.|
|SFT (extrapleural)||Deep-seated and variably located soft tissue tumor of adults. Often slow growing.||Cellular or moderate yield. Uniform spindled cells having scanty unipolar or bipolar cytoplasm. Cells are dissociated or arranged in fascicles with haphazard or occasionally a storiform pattern. Stripped nuclei and collagen matrix fragments in the background.|
|FH (cellular)||Usually superficial but extending often deep into the subcutis. Larger than 2.0 cm and arising in the extremities or head and neck of young adults.||Variable, most often cellular yield. Dispersed cells and small fascicles/clusters of uniform or slightly pleomorphic spindled cells with indistinct cytoplasm borders, mixed with histiocytes and occasional multinucleated cells.|
|SCL||Small or medium-sized subcutaneous mass, seated in the neck, back, or shoulder of middle-aged men. Long history.||Variable yield. Strands of uniform spindled cells, fat tissue, and collagen bundles/fibers in variable proportions. Long, slender, acellular collagen fibers are common. Often a myxoid background with mast cells.|
|Extraabdominal desmoid (fibromatosis)||Infiltrative mass, which can be deep subcutaneous or intramuscular. Usually in the proximal extremities or limb girdles of adults. Often larger than 5.0 cm.||Variable yield. Clusters of dissociated spindled cells with indistinct cytoplasm and some cytoplasmic processes. Uniform, spindled, or fusiform nuclei, sometimes with moderate anisokaryosis. Stripped nuclei and fragments of more or less cellular collagenous tissue common. Occasional striated-muscle giant cells.|
|Synovial sarcoma||Often arise close to a large joint in the extremities and limb girdles in young adults and teenagers. Can occur at almost any age and in any location. Often long history.||Cellular yield. Mixture of tight sheets or clusters and dispersed small to medium sized, often bland-looking cells with spindle/ovoid or rounded nuclei and scanty unipolar or bipolar cytoplasm. Nucleoli are inconspicuous and chromatin is finely granular. Capillary vessels within cell-clusters and mast cells may be present.|
|MFS (myxoid MFH)||Usually subcutaneous in the extremities and arising in adults (often older than 50).||Cellular yield. Abundant myxoid background with aggregated or dissociated spindle cells with variable pleomorphism (depending on malignancy grade). Smears from high-grade MFS display highly pleomorphic cells and mitoses. Low-grade MFS can be dominated by moderately atypical spindle cells. Curved vessels are often seen. Inadvertently aspirated benign subcutaneous fat may be present.|
|AFX (cutaneous MFH)||Small or medium-sized skin nodules, arising predominantly in elderly patients on the head, face and neck, occasionally on the trunk and extremities.||Smears from AFX resemble those from MFH of pleomorphic and storiform type. Myxoid matrix may be present.|
|Metastatic SCM||Variably located and most common in adults/elderly patients||Variable, usually cellular yield. Slightly or moderately pleomorphic spindle cells with stellate cytoplasm which are dissociated or in small fascicles. Binucleated cells and nuclear incusions can be found in smears.|
|Fibrosarcoma||Uncommon, slow-growing tumor, typically seated in the deep soft tissue of extremities and trunk in adults.||Variable yield. Slightly atypical spindled cells with fusiform, slender nuclei and scanty, elongated cytoplasm. Cells are dissociated or arranged in fascicles.|
Spindle cell lipoma is a benign neoplasm that displays monomorphic spindle cells mixed with fat and collagenous fibers in smears.17 SCL containing predominantly spindle cells may be difficult to distinguish from DFSP, as the spindle cells in both entities have a similar morphology and immunohistochemical profile. Electron microscopic (EM) examination of aspirated material may be helpful as spindle cells in the SCL usually show differentiation toward prelipoblasts. Another clue is the presence of bright staining fragments of collagen matrix, which are found frequently in smears from patients with SCL.17 The clinical presentation is also helpful in differentiating these two tumors. SCL is typically located in the subcutaneous tissue of the back, neck, or shoulder in men older than 40. DFSP is a slow-growing, superficially located, sometimes multinodular, protuberant skin mass that presents most often in the trunk in adults of either sex between the ages of 30 and 50 years.18
Another differential diagnosis is NF, which in its late stage yields a population of monomorphic cells arranged in cell clusters or dissociated cells similar to DFSP. Late NF is almost undistinguishable from DFSP in routinely stained smears (Fig. 6A). Some inflammatory and “ganglion-like” cells are usually identified (Fig. 6B). The clinical appearance of NF is different from that of DFSP, as NF is a rapidly growing and, in most cases, a spontaneously regressing lesion.19, 20 Immunostaining with CD34 and smooth muscle actin (SMA) is also helpful in differentiating DFSP from NF.
Smears from benign tumors of neural origin (e.g., neurilemoma, neurofibroma, and perineurioma), which can show morphologic overlapping with DFSP, are other differential diagnoses.21, 22 It is important to have access to immunocytochemistry, which can easily distinguish between fibrohistiocytic and neurogenic spindle cell tumors. Case 8 illustrates the need for reliable immunocytochemistry in the FNA evaluation of spindle cell tumors. FNA of the lesion gave cellular smears with clustered and dissociated bland spindle cells, fitted well in the low-grade spindle cell sarcoma category, and was suspected to be DFSP. The deep tumor location, however, was unusual for DFSP. Because there was some difficulty in performing additional aspirates for cell block preparation, smears were used for immunocytochemistry. The results of stainings for CD34, EMA, CD99, and S-100 were difficult to interpret due to heavy background staining in the cell clusters. The final cytologic diagnosis was low-grade spindle cell sarcoma, DFSP versus synovial sarcoma versus low-grade malignant peripheral nerve sheath tumor. Histologically, the excised tumor was an unusual deeply located (without connection to the skin) DFSP with incipient fibrosarcomatous areas (Fig. 5A–C). The tumor cells were clearly positive for CD34 in sections taken from the paraffin blocks.
Smears from FH, especially the cellular variant,23 can be confused easily with DFSP (Fig. 7A,B). Cellular FH presents often as a relatively rapidly growing (months) mass with a predilection for the limbs, head, and neck, which is different from DFSP. Identification of plump histiocytes and giant cells, as well as negative staining for CD34 and positive for alpha SMA in most cases, helps to exclude DFSP.
Extraabdominal desmoids (fibromatoses) are also used in the differential diagnosis of DFSP. Most fibromatoses are more deeply located than DFSP and yield sparse material consisting of bland-looking, predominantly dissociated fibroblasts with better preserved cytoplasm, compared with the spindle cells in smears from DFSP. In addition, spindle cells in fibromatoses are mixed with acellular, collagenous stromal fragments.25, 26 They usually show positive immunostaining for SMA, but are negative for CD34.
Metastatic SCM and synovial sarcoma are two malignant tumors that can mimic DFSP cytologically. In most cases, smears from metastatic SCM are composed predominantly of dissociated spindle cells positive for S-100 and HMB45. A few binucleated cells and nuclear inclusions are sometimes found in the smears. Melanin pigment is visible occasionally (Fig. 9). Synovial sarcomas, which are similar to DFSP, yield cellular smears with poorly cohesive clusters and dissociated bland-looking spindle cells27 (Fig. 10A) that are positive for CD99 and focally positive for EMA and keratin (Fig. 10B). The presence of a herringbone pattern (Fig. 10C) and cytogenetic analysis of aspirated material also may be of help because most synovial sarcomas show an X;18 translocation (Fig. 10D). Atypical fibroxanthoma (AFX), also called cutaneous malignant fibrous histiocytoma (MFH), may appear clinically similar to DFSP. Smears from AFX resemble those from storiform and pleomorphic MFH.28, 29 Smears from DFSP are more monomorphic, which enables the differentiation of AFX from DFSP.
Reports of FNAB of DFSP stress that smear patterns are helpful in the evaluation.11, 12, 14 The storiform pattern in fascicles of spindle cells in our study was noted in nine aspirates. However, a storiform pattern is not exclusive to smears of DFSP and may be observed occasionally in other spindle cell lesions such as NF, FH, MFH, SFT, and synovial sarcoma. Berardo et al.30 mentioned that a prominent storiform pattern appeared in 10 smears in their series of 52 MFH. In these cases, however, most of the smears presented at least some features of high-grade morphology. These authors could not define any distinctive cytologic criteria specific for MFH. Their smears frequently showed not only a spindle cell morphology but one or two additional cell types including large, pleomorphic and multinucleated giant cells. In addition, five smears had a myxoid stroma, a feature of the myxoid variety of MFH-myxofibrosarcoma (MFS). Smears from DFSP do not display an abundant myxoid background, which differentiates them from low-grade MFS. In addition, the latter usually give a smear with rather dispersed cells with moderate atypia.31
It is important to point out that the same rules used in the evaluation of biopsy specimens should be applied to cytologic material. Therefore, it is important to obtain adequate aspiration material, not only for routine smears but also for ancillary studies such as immunostaining, EM, and for cytogenetic examination. This requires correct management of the patients from the outset with optimal aspiration technique and the availability of ancillary techniques, if needed. Under such circumstances, evaluation of spindle cell lesions by FNA is not inferior to evaluation by open biopsy. It is important, however, that the cytopathologist requests an open biopsy as soon as it is seen that the cytologic material is insufficient for diagnosis.
The most frequent type of FNA aspirate from DFSP in the current study was cellular with compact spindle cell clusters embedded in collagenous and occasionally myxoid matrix. In addition, there was a component of dissociated spindle cells and naked nuclei. Three cases of fibrosarcomatous DFSP included in this study showed no evident cytomorphologic clues of high malignant potential. The examination of FNA smears alone gave no help in differentiating DFSP from its high-grade, fibrosarcomatous counterpart.
In summary, as DFSP shares some cytologic features with a variety of other spindle cell lesions both benign and malignant, it is difficult to render precise histotypic diagnoses from cytologic smears alone. As in the evaluation of other spindle cell lesions, ancillary studies performed on FNA specimens together with proper clinical information is crucial in the cytologic evaluation of DFSP.
- 24Solitary fibrous tumor of the soft tissue [Abstract]. The 25th Meeting of the Scandinavian Sarcoma Group, Oslo, April 21–23, 1999., , , .
- 27Fine needle aspiration (FNA) of synovial sarcoma- a comparative histological-cytological study of 15 cases, including immunohistochemical, electron microscopic and cytogenetic examination and DNA-ploidy analysis. Cytopathology. 1996; 7: 187–200., , , , .
- 29Benign and malignant soft tissue tumors. In: GrayW, editor, Diagnostic cytopathology. Hong Kong: Churchill Livingstone, 1995; 851–871..