Novel Insights from Clinical Practice Acta Cytologica 2015;59:113–117 DOI: 10.1159/000369855
Received: August 22, 2014 Accepted after revision: November 11, 2014 Published online: December 24, 2014
Fine-Needle Aspiration Cytology of Disseminated Kaposi Sarcoma of the Bone in an AIDS Patient Oleksandr Yergiyev a Alok Mohanty a Sheilah Curran-Melendez b Carmen R. Latona b Rama Bhagavatula c Larisa Greenberg c Jan F. Silverman a Departments of a Pathology and Laboratory Medicine, b Radiology, and c Medical Oncology, Allegheny General Hospital, Pittsburgh, Pa., USA
Established Facts • Kaposi sarcoma (KS) is a neoplasm of vascular origin that may present as one of four clinical and epidemiologic forms and is uniformly associated with human herpesvirus 8 (HHV-8). • Bone involvement, although rare, can occur in patients with any form of KS.
Novel Insights • KS has distinctive cytomorphology that, in the setting of appropriate history, sets it apart from other conditions that can present as multiple lytic lesions of the skeleton. • Patients with disseminated skeletal KS may undergo fine-needle aspiration (FNA) of a bone lesion as the first line of diagnostic workup. • Ancillary immunohistochemical studies for vascular markers and HHV-8 can be useful in confirming the diagnosis of KS in FNA biopsy. • FNA cytology can make a definitive diagnosis of skeletal KS.
Abstract Background: Kaposi sarcoma (KS) is a vascular neoplasm associated with human herpesvirus 8 (HHV-8). Skin and mucous membranes are the most common sites, but other organs may be involved. Skeletal KS is rare and occurs either by direct spread of mucocutaneous lesions or through dis-
© 2014 S. Karger AG, Basel 0001–5547/14/0591–0113$39.50/0 E-Mail [email protected] www.karger.com/acy
semination. Patients present with bone pain and lytic lesions for which they may undergo fine-needle aspiration (FNA). While there are about 70 published case reports of skeletal KS, there is limited literature specifically describing its cytomorphology. Our literature search yielded only a single prior reported case of FNA biopsy of skeletal KS in a Nigerian AIDS patient. Case: We present a case of disseminated KS of the axial skeleton in a 45-year-old African-American man with AIDS which was diagnosed on FNA cytologic examination. The patient presented with multiple lytic lesions in the axial skeleton. The aspirate, core-needle biopsy and touch imprint
Correspondence to: Dr. Jan F. Silverman Department of Pathology and Laboratory Medicine, Allegheny General Hospital 320 East North Avenue Pittsburgh, PA 15212 (USA) E-Mail jsilverm @ wpahs.org
Downloaded by: Univ. of Michigan, Taubman Med.Lib. 198.143.32.1 - 6/26/2015 4:27:59 PM
Key Words Kaposi sarcoma · Bone lesion · Fine-needle aspiration · Fine-needle cytology
cytology of a bone lesion demonstrated clusters of spindle and epithelioid cells in radial and streaming arrangement with indistinct intercytoplasmic borders, elongated nuclei, fine chromatin and inconspicuous nucleoli. Immunohistochemical studies revealed positivity for HHV-8 and vascular markers. The cytomorphologic and ancillary features of the case are presented and discussed. © 2014 S. Karger AG, Basel
Introduction
114
Acta Cytologica 2015;59:113–117 DOI: 10.1159/000369855
Fig. 1. Unenhanced axial CT image of the pelvis demonstrates multiple osteolytic lesions within the sacrum and left iliac wing.
logic findings. We present a detailed cytologic report of KS in a 45-year-old African-American HIV-positive patient in whom the diagnosis was made on FNA biopsy. To our knowledge, this is the first detailed report of FNA cytomorphologic findings in a Western AIDS patient with skeletal lesions.
Case Report The patient was a 45-year-old African-American male with AIDS and recently diagnosed cutaneous KS of the left and right thigh. The patient’s last known HIV viral load was 33,440 one month prior to the current presentation, with a helper-to-cytotoxic T cell ratio of 0.08. Computed tomography (CT) evaluation revealed multiple round, well-demarcated lytic lesions involving vertebral bodies, the sacrum and bilateral iliac wings (fig. 1). No pathologic fractures were seen. Extensive bilateral cervical lymphadenopathy was also noted. Based on the radiologic findings, the initial differential diagnosis included osseous KS, lymphoma and multiple myeloma. A bone marrow aspiration was performed, and flow cytometry results did not support a diagnosis of plasma cell dyscrasia, lymphoproliferative disorder or acute leukemia. The patient then underwent an FNA and a core-needle biopsy with touch imprint cytologic evaluation of a left iliac bone lesion. The cytomorphologic and immunohistochemical findings were consistent with osseous involvement in KS. The patient was started on liposomal doxorubicin and HAART (highly active antiretroviral therapy). At the patient’s most recent follow-up 2 months after the diagnosis he demonstrated a response to the therapy with stable osseous lesions and a decrease in lymphadenopathy.
Yergiyev et al.
Downloaded by: Univ. of Michigan, Taubman Med.Lib. 198.143.32.1 - 6/26/2015 4:27:59 PM
Kaposi sarcoma (KS) is a locally aggressive neoplastic or pseudoneoplastic lesion of vascular origin. There are four recognized clinical and epidemiologic forms of KS – classic, endemic African, iatrogenic and acquired immune deficiency syndrome (AIDS) related. All four forms are uniformly associated with human herpesvirus 8 (HHV-8) infection [1]. The natural history of KS typically progresses through the consecutive stages of macule (patch), plaque and nodule. While skin and mucous membranes are the most common sites of involvement, the involvement of other organs is not uncommon. The skeleton is an unusual site for KS lesions [1, 2]. A recent comprehensive review of KS involving the musculoskeletal system identified 66 such cases during the time period between 1925 and 2006 [3]. Any form of KS can manifest with skeletal lesions. Regardless of the clinical and epidemiologic features, osseous KS lesions are almost invariably associated with a history of preexisting or concomitant cutaneous or mucosal KS [2, 3]. In patients with classical and African forms of KS the bone lesions usually represent direct involvement by the overlying cutaneous or mucosal KS. In contrast, patients with AIDS-related KS typically have cutaneous lesions distant from the site of bone involvement, as well as frequent disseminated visceral disease. There is a propensity for axial skeleton involvement in AIDS-related KS, in contrast to the long bones of the extremities in classical and African KS. Although bone involvement by KS may be asymptomatic in some patients, it typically causes localized bone pain and may limit mobility. Joint involvement and KS-associated pathologic fractures are exceptional [2, 3]. Despite a number of reported cases of skeletal involvement in KS, our search rendered only a single prior report describing fine-needle aspiration (FNA) biopsy findings. This patient report was published in an infectious disease journal, and describes cell block findings in skeletal KS in a Nigerian human immunodeficiency virus (HIV)-positive man [4], but does not report any cyto-
Materials and Methods Immediately before the procedure, a limited CT scan was obtained, which confirmed the presence of multiple lytic lesions in the left iliac bone. Based on the scan, a site for accessing a lesion was selected and marked. As a local anesthetic, 2% lidocaine was used in combination with conscious sedation. A small skin nick was made, and an 11-gauge Vidacare (Shavano Park, Tex., USA) bone biopsy needle was passed through the skin and directed toward the left iliac bone targeting one of the lytic lesions. A control CT scan was obtained and based on it the position of the needle was adjusted until the needle tip abutted the cortex adjacent to the lesion. The needle was then advanced through the cortex and into the lesion using a Vidacare drill. Once CT demonstrated that the needle had passed into the lesion, a core biopsy was obtained. The bone biopsy needle was then retracted under CT guidance just proximal to the lesion. The central trocar was removed, and two fine-needle aspirates were obtained. Direct smears from the aspirates were prepared in the radiology suite. A matching pair of ethanol-fixed and air-dried slides was prepared for each FNA pass. The air-dried slides were stained with Diff-Quik stain and used for immediate cytologic evaluation. In addition, Diff-Quik-stained air-dried touch imprint of the initial core biopsy was used for immediate evaluation in conjunction with the FNA direct smears. Following cytologic confirmation of the presence of diagnostic tissue, further core biopsies and aspirates were acquired, to a total number of five core biopsies and four fine-needle aspirates. The air-dried slides were stained with Diff-Quik stain, and the alcoholfixed slides were subsequently stained with Papanicolaou stain. FNA needle rinsings were placed in Roswell Park Memorial Institute medium (RPMI-1640), spun down and processed into a cell block. Cell block paraffin sections of 4 μm were stained with hematoxylin and eosin (HE) stain. The core biopsy tissue was placed
FNA of Disseminated KS of the Bone
Fig. 3. Lesion cells with epithelioid and spindle morphology, fine chromatin and indistinct ‘syncytial’ intercytoplasmic borders. Diff-Quik stain. Original magnification ×400.
in 10% buffered neutral formalin, and 4-μm paraffin sections of the cores were stained with HE. Immunohistochemical (IHC) stains for HHV-8, CD31, CD34 and factor VIII were also performed on sections of the cores, along with special stains for microorganisms (Ziehl-Neelsen and Warthin-Starry).
Results
Cytologic Findings Both the direct FNA smears and the touch imprint cytology smears were moderately cellular and contained scattered three-dimensional cellular groups composed of bland spindle and epithelioid cells. A moderate amount of crush artifact was seen in some of the groups. In addition, the FNA smears showed a background of trilineage hematopoiesis. Some of the cellular groups showed radial arrangement of spindle cells, while others demonstrated cellular streaming and vascular cores traversing through the fragments (fig. 2). The degree of atypia within the cellular groups was minimal. The nuclei were elongated and plump with finely granular chromatin and inconspicuous nucleoli. Mitotic figures were rare. The nuclear-to-cytoplasmic ratios were not significantly elevated. The intercellular cytoplasmic borders were indistinct, and many fragments had a syncytial appearance. Cytoplasmic tapering could be appreciated at the edges of the fragments (fig. 3, 4). Hyaline globules were seen in some fragments with Diff-Quik stain. Acta Cytologica 2015;59:113–117 DOI: 10.1159/000369855
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Fig. 2. Three-dimensional clusters of spindle and epithelioid cells with streaming arrangement. Papanicolaou stain. Original magnification ×600.
a
Fig. 4. Cluster of spindle cells in radial and streaming arrangement.
Diff-Quik stain. Original magnification ×400.
Fig. 5. Paraffin section of core biopsy demonstrates a lesion com-
posed of spindle and epithelioid cells forming a network of anastomosing vascular channels. Intracytoplasmic lumina containing red blood cells are seen along with extravasated red blood cells. A mitotic figure is present in the center of the field next to a cluster of hyaline globules. HE stain. Original magnification ×400.
b
Fig. 6. Lesion cells demonstrate cytoplasmic positivity for CD31 (a) and nuclear positivity for HHV-8 (b). Original magnification ×400.
tertrabecular foci of spindle cell proliferation. These were composed of mildly atypical spindle cells that formed a delicate branching anastomosing network of vascular spaces. The cell morphology corresponded to that seen in the cytology preparations, with intermediate nuclear-tocytoplasmic ratios, elongated-to-curved nuclei, finely granular chromatin and inconspicuous nucleoli. The cytoplasm was eosinophilic with indistinct cytoplasmic borders. Intracytoplasmic vascular spaces could be seen in some cells. Some of the intracytoplasmic lumina contained red blood cells (RBCs). RBCs were also seen within the anastomosing vascular channels, extravasated RBCs were a conspicuous feature, and hyaline globules were focally present. Mitoses were rare (fig. 5). Adjacent bone trabeculae exhibited prominent osteoblastic rimming consistent with active bone remodeling. IHC stain for HHV-8 showed strong nuclear positivity in approximately 20% of lesion cells. The IHC stains for CD31, CD34 and factor VIII were also positive (fig. 6). ZiehlNeelsen and Warthin-Starry stains were negative for acid-fast bacilli and Bartonella, respectively.
Discussion
116
Acta Cytologica 2015;59:113–117 DOI: 10.1159/000369855
KS is a vascular proliferation of presumably neoplastic nature that is uniformly associated with HHV-8. Four clinical and epidemiologic forms are recognized. The majority of patients present with cutaneous and mucosal leYergiyev et al.
Downloaded by: Univ. of Michigan, Taubman Med.Lib. 198.143.32.1 - 6/26/2015 4:27:59 PM
Histologic Findings Tissue sections of the core biopsy contained cortical and trabecular bone with hypercellular marrow (approximately 80% cellularity) with normal trilineage hematopoiesis. There were two relatively well-circumscribed in-
References
FNA of Disseminated KS of the Bone
cells arranged in radial fashion around delicate central vascular channels. The cells have a syncytial appearance with indistinct cytoplasmic borders and elongated or curved nuclei with fine chromatin and inconspicuous nucleoli. Extravasated RBCs and hyaline globules are other features seen in cytology preparations of KS. Appreciation of these findings in an aspirate of a lytic bone lesion from an HIV-positive patient should direct the cytopathologist towards a neoplasm of vascular lineage and prompt appropriate workup. IHC stains for HHV-8 and vascular markers are useful in confirming the diagnosis. We believe this is the first detailed report of skeletal KS diagnosed by FNA cytology.
Disclosure Statement The authors have no conflicts of interest.
1 Mentzel T, Knuutila S, Lamovec J: Kaposi sarcoma; in Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds): WHO Classification of Tumours of Soft Tissue and Bone, ed 4. Lyon, International Agency for Research on Cancer, 2013, pp 151–153. 2 Pantanowitz L, Dezube BJ: Kaposi sarcoma in unusual locations. BMC Cancer 2008;8:190. 3 Caponetti G, Dezube BJ, Restrepo CS, Pantanowitz L: Kaposi sarcoma of the musculoskeletal system: a review of 66 patients. Cancer 2007;109:1040–1052.
4 Di Bella S, Capone A, Olearo F, Johnson E, Chinello P, Baiocchini A, Del Nonno F, Busi Rizzi E, Petrosillo N: Vertebral lesions from AIDS-related Kaposi’s sarcoma. Curr HIV Res 2011;9:270–275. 5 Gamborino E, Carrilho C, Ferro J, Khan MS, Garcia C, Suarez MC, Yokoyama H, Schmitt FC: Fine-needle aspiration diagnosis of Kaposi’s sarcoma in a developing country. Diagn Cytopathol 2000;23:322–325.
Acta Cytologica 2015;59:113–117 DOI: 10.1159/000369855
117
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sions, but visceral involvement is not uncommon. The skeleton is one of the least common sites to be involved by KS, and patients with any clinical and epidemiologic form of KS may manifest with osseous lesions. Skeletal KS lesions typically cause vague bone pain although patients can be asymptomatic. In AIDS-associated KS, osseous lesions are not necessarily a result of direct involvement by mucocutaneous KS, but rather represent disseminated disease. The differential diagnosis of multiple lytic bone lesions is broad and includes, depending on the patient’s demographics, multiple myeloma, metastatic carcinoma and, specifically in HIV-positive patients, bacillary angiomatosis and other infectious processes. FNA cytology is not infrequently the first choice in the diagnostic workup of patients with multiple lytic bone lesions. KS is an important diagnosis to be considered in an HIV-positive patient. Cytologic preparations obtained from KS lesions of the bone have distinct morphology with bland spindle
Received: August 22, 2014 Accepted after revision: November 11, 2014 Published online: December 24, 2014
Fine-Needle Aspiration Cytology of Disseminated Kaposi Sarcoma of the Bone in an AIDS Patient Oleksandr Yergiyev a Alok Mohanty a Sheilah Curran-Melendez b Carmen R. Latona b Rama Bhagavatula c Larisa Greenberg c Jan F. Silverman a Departments of a Pathology and Laboratory Medicine, b Radiology, and c Medical Oncology, Allegheny General Hospital, Pittsburgh, Pa., USA
Established Facts • Kaposi sarcoma (KS) is a neoplasm of vascular origin that may present as one of four clinical and epidemiologic forms and is uniformly associated with human herpesvirus 8 (HHV-8). • Bone involvement, although rare, can occur in patients with any form of KS.
Novel Insights • KS has distinctive cytomorphology that, in the setting of appropriate history, sets it apart from other conditions that can present as multiple lytic lesions of the skeleton. • Patients with disseminated skeletal KS may undergo fine-needle aspiration (FNA) of a bone lesion as the first line of diagnostic workup. • Ancillary immunohistochemical studies for vascular markers and HHV-8 can be useful in confirming the diagnosis of KS in FNA biopsy. • FNA cytology can make a definitive diagnosis of skeletal KS.
Abstract Background: Kaposi sarcoma (KS) is a vascular neoplasm associated with human herpesvirus 8 (HHV-8). Skin and mucous membranes are the most common sites, but other organs may be involved. Skeletal KS is rare and occurs either by direct spread of mucocutaneous lesions or through dis-
© 2014 S. Karger AG, Basel 0001–5547/14/0591–0113$39.50/0 E-Mail [email protected] www.karger.com/acy
semination. Patients present with bone pain and lytic lesions for which they may undergo fine-needle aspiration (FNA). While there are about 70 published case reports of skeletal KS, there is limited literature specifically describing its cytomorphology. Our literature search yielded only a single prior reported case of FNA biopsy of skeletal KS in a Nigerian AIDS patient. Case: We present a case of disseminated KS of the axial skeleton in a 45-year-old African-American man with AIDS which was diagnosed on FNA cytologic examination. The patient presented with multiple lytic lesions in the axial skeleton. The aspirate, core-needle biopsy and touch imprint
Correspondence to: Dr. Jan F. Silverman Department of Pathology and Laboratory Medicine, Allegheny General Hospital 320 East North Avenue Pittsburgh, PA 15212 (USA) E-Mail jsilverm @ wpahs.org
Downloaded by: Univ. of Michigan, Taubman Med.Lib. 198.143.32.1 - 6/26/2015 4:27:59 PM
Key Words Kaposi sarcoma · Bone lesion · Fine-needle aspiration · Fine-needle cytology
cytology of a bone lesion demonstrated clusters of spindle and epithelioid cells in radial and streaming arrangement with indistinct intercytoplasmic borders, elongated nuclei, fine chromatin and inconspicuous nucleoli. Immunohistochemical studies revealed positivity for HHV-8 and vascular markers. The cytomorphologic and ancillary features of the case are presented and discussed. © 2014 S. Karger AG, Basel
Introduction
114
Acta Cytologica 2015;59:113–117 DOI: 10.1159/000369855
Fig. 1. Unenhanced axial CT image of the pelvis demonstrates multiple osteolytic lesions within the sacrum and left iliac wing.
logic findings. We present a detailed cytologic report of KS in a 45-year-old African-American HIV-positive patient in whom the diagnosis was made on FNA biopsy. To our knowledge, this is the first detailed report of FNA cytomorphologic findings in a Western AIDS patient with skeletal lesions.
Case Report The patient was a 45-year-old African-American male with AIDS and recently diagnosed cutaneous KS of the left and right thigh. The patient’s last known HIV viral load was 33,440 one month prior to the current presentation, with a helper-to-cytotoxic T cell ratio of 0.08. Computed tomography (CT) evaluation revealed multiple round, well-demarcated lytic lesions involving vertebral bodies, the sacrum and bilateral iliac wings (fig. 1). No pathologic fractures were seen. Extensive bilateral cervical lymphadenopathy was also noted. Based on the radiologic findings, the initial differential diagnosis included osseous KS, lymphoma and multiple myeloma. A bone marrow aspiration was performed, and flow cytometry results did not support a diagnosis of plasma cell dyscrasia, lymphoproliferative disorder or acute leukemia. The patient then underwent an FNA and a core-needle biopsy with touch imprint cytologic evaluation of a left iliac bone lesion. The cytomorphologic and immunohistochemical findings were consistent with osseous involvement in KS. The patient was started on liposomal doxorubicin and HAART (highly active antiretroviral therapy). At the patient’s most recent follow-up 2 months after the diagnosis he demonstrated a response to the therapy with stable osseous lesions and a decrease in lymphadenopathy.
Yergiyev et al.
Downloaded by: Univ. of Michigan, Taubman Med.Lib. 198.143.32.1 - 6/26/2015 4:27:59 PM
Kaposi sarcoma (KS) is a locally aggressive neoplastic or pseudoneoplastic lesion of vascular origin. There are four recognized clinical and epidemiologic forms of KS – classic, endemic African, iatrogenic and acquired immune deficiency syndrome (AIDS) related. All four forms are uniformly associated with human herpesvirus 8 (HHV-8) infection [1]. The natural history of KS typically progresses through the consecutive stages of macule (patch), plaque and nodule. While skin and mucous membranes are the most common sites of involvement, the involvement of other organs is not uncommon. The skeleton is an unusual site for KS lesions [1, 2]. A recent comprehensive review of KS involving the musculoskeletal system identified 66 such cases during the time period between 1925 and 2006 [3]. Any form of KS can manifest with skeletal lesions. Regardless of the clinical and epidemiologic features, osseous KS lesions are almost invariably associated with a history of preexisting or concomitant cutaneous or mucosal KS [2, 3]. In patients with classical and African forms of KS the bone lesions usually represent direct involvement by the overlying cutaneous or mucosal KS. In contrast, patients with AIDS-related KS typically have cutaneous lesions distant from the site of bone involvement, as well as frequent disseminated visceral disease. There is a propensity for axial skeleton involvement in AIDS-related KS, in contrast to the long bones of the extremities in classical and African KS. Although bone involvement by KS may be asymptomatic in some patients, it typically causes localized bone pain and may limit mobility. Joint involvement and KS-associated pathologic fractures are exceptional [2, 3]. Despite a number of reported cases of skeletal involvement in KS, our search rendered only a single prior report describing fine-needle aspiration (FNA) biopsy findings. This patient report was published in an infectious disease journal, and describes cell block findings in skeletal KS in a Nigerian human immunodeficiency virus (HIV)-positive man [4], but does not report any cyto-
Materials and Methods Immediately before the procedure, a limited CT scan was obtained, which confirmed the presence of multiple lytic lesions in the left iliac bone. Based on the scan, a site for accessing a lesion was selected and marked. As a local anesthetic, 2% lidocaine was used in combination with conscious sedation. A small skin nick was made, and an 11-gauge Vidacare (Shavano Park, Tex., USA) bone biopsy needle was passed through the skin and directed toward the left iliac bone targeting one of the lytic lesions. A control CT scan was obtained and based on it the position of the needle was adjusted until the needle tip abutted the cortex adjacent to the lesion. The needle was then advanced through the cortex and into the lesion using a Vidacare drill. Once CT demonstrated that the needle had passed into the lesion, a core biopsy was obtained. The bone biopsy needle was then retracted under CT guidance just proximal to the lesion. The central trocar was removed, and two fine-needle aspirates were obtained. Direct smears from the aspirates were prepared in the radiology suite. A matching pair of ethanol-fixed and air-dried slides was prepared for each FNA pass. The air-dried slides were stained with Diff-Quik stain and used for immediate cytologic evaluation. In addition, Diff-Quik-stained air-dried touch imprint of the initial core biopsy was used for immediate evaluation in conjunction with the FNA direct smears. Following cytologic confirmation of the presence of diagnostic tissue, further core biopsies and aspirates were acquired, to a total number of five core biopsies and four fine-needle aspirates. The air-dried slides were stained with Diff-Quik stain, and the alcoholfixed slides were subsequently stained with Papanicolaou stain. FNA needle rinsings were placed in Roswell Park Memorial Institute medium (RPMI-1640), spun down and processed into a cell block. Cell block paraffin sections of 4 μm were stained with hematoxylin and eosin (HE) stain. The core biopsy tissue was placed
FNA of Disseminated KS of the Bone
Fig. 3. Lesion cells with epithelioid and spindle morphology, fine chromatin and indistinct ‘syncytial’ intercytoplasmic borders. Diff-Quik stain. Original magnification ×400.
in 10% buffered neutral formalin, and 4-μm paraffin sections of the cores were stained with HE. Immunohistochemical (IHC) stains for HHV-8, CD31, CD34 and factor VIII were also performed on sections of the cores, along with special stains for microorganisms (Ziehl-Neelsen and Warthin-Starry).
Results
Cytologic Findings Both the direct FNA smears and the touch imprint cytology smears were moderately cellular and contained scattered three-dimensional cellular groups composed of bland spindle and epithelioid cells. A moderate amount of crush artifact was seen in some of the groups. In addition, the FNA smears showed a background of trilineage hematopoiesis. Some of the cellular groups showed radial arrangement of spindle cells, while others demonstrated cellular streaming and vascular cores traversing through the fragments (fig. 2). The degree of atypia within the cellular groups was minimal. The nuclei were elongated and plump with finely granular chromatin and inconspicuous nucleoli. Mitotic figures were rare. The nuclear-to-cytoplasmic ratios were not significantly elevated. The intercellular cytoplasmic borders were indistinct, and many fragments had a syncytial appearance. Cytoplasmic tapering could be appreciated at the edges of the fragments (fig. 3, 4). Hyaline globules were seen in some fragments with Diff-Quik stain. Acta Cytologica 2015;59:113–117 DOI: 10.1159/000369855
115
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Fig. 2. Three-dimensional clusters of spindle and epithelioid cells with streaming arrangement. Papanicolaou stain. Original magnification ×600.
a
Fig. 4. Cluster of spindle cells in radial and streaming arrangement.
Diff-Quik stain. Original magnification ×400.
Fig. 5. Paraffin section of core biopsy demonstrates a lesion com-
posed of spindle and epithelioid cells forming a network of anastomosing vascular channels. Intracytoplasmic lumina containing red blood cells are seen along with extravasated red blood cells. A mitotic figure is present in the center of the field next to a cluster of hyaline globules. HE stain. Original magnification ×400.
b
Fig. 6. Lesion cells demonstrate cytoplasmic positivity for CD31 (a) and nuclear positivity for HHV-8 (b). Original magnification ×400.
tertrabecular foci of spindle cell proliferation. These were composed of mildly atypical spindle cells that formed a delicate branching anastomosing network of vascular spaces. The cell morphology corresponded to that seen in the cytology preparations, with intermediate nuclear-tocytoplasmic ratios, elongated-to-curved nuclei, finely granular chromatin and inconspicuous nucleoli. The cytoplasm was eosinophilic with indistinct cytoplasmic borders. Intracytoplasmic vascular spaces could be seen in some cells. Some of the intracytoplasmic lumina contained red blood cells (RBCs). RBCs were also seen within the anastomosing vascular channels, extravasated RBCs were a conspicuous feature, and hyaline globules were focally present. Mitoses were rare (fig. 5). Adjacent bone trabeculae exhibited prominent osteoblastic rimming consistent with active bone remodeling. IHC stain for HHV-8 showed strong nuclear positivity in approximately 20% of lesion cells. The IHC stains for CD31, CD34 and factor VIII were also positive (fig. 6). ZiehlNeelsen and Warthin-Starry stains were negative for acid-fast bacilli and Bartonella, respectively.
Discussion
116
Acta Cytologica 2015;59:113–117 DOI: 10.1159/000369855
KS is a vascular proliferation of presumably neoplastic nature that is uniformly associated with HHV-8. Four clinical and epidemiologic forms are recognized. The majority of patients present with cutaneous and mucosal leYergiyev et al.
Downloaded by: Univ. of Michigan, Taubman Med.Lib. 198.143.32.1 - 6/26/2015 4:27:59 PM
Histologic Findings Tissue sections of the core biopsy contained cortical and trabecular bone with hypercellular marrow (approximately 80% cellularity) with normal trilineage hematopoiesis. There were two relatively well-circumscribed in-
References
FNA of Disseminated KS of the Bone
cells arranged in radial fashion around delicate central vascular channels. The cells have a syncytial appearance with indistinct cytoplasmic borders and elongated or curved nuclei with fine chromatin and inconspicuous nucleoli. Extravasated RBCs and hyaline globules are other features seen in cytology preparations of KS. Appreciation of these findings in an aspirate of a lytic bone lesion from an HIV-positive patient should direct the cytopathologist towards a neoplasm of vascular lineage and prompt appropriate workup. IHC stains for HHV-8 and vascular markers are useful in confirming the diagnosis. We believe this is the first detailed report of skeletal KS diagnosed by FNA cytology.
Disclosure Statement The authors have no conflicts of interest.
1 Mentzel T, Knuutila S, Lamovec J: Kaposi sarcoma; in Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds): WHO Classification of Tumours of Soft Tissue and Bone, ed 4. Lyon, International Agency for Research on Cancer, 2013, pp 151–153. 2 Pantanowitz L, Dezube BJ: Kaposi sarcoma in unusual locations. BMC Cancer 2008;8:190. 3 Caponetti G, Dezube BJ, Restrepo CS, Pantanowitz L: Kaposi sarcoma of the musculoskeletal system: a review of 66 patients. Cancer 2007;109:1040–1052.
4 Di Bella S, Capone A, Olearo F, Johnson E, Chinello P, Baiocchini A, Del Nonno F, Busi Rizzi E, Petrosillo N: Vertebral lesions from AIDS-related Kaposi’s sarcoma. Curr HIV Res 2011;9:270–275. 5 Gamborino E, Carrilho C, Ferro J, Khan MS, Garcia C, Suarez MC, Yokoyama H, Schmitt FC: Fine-needle aspiration diagnosis of Kaposi’s sarcoma in a developing country. Diagn Cytopathol 2000;23:322–325.
Acta Cytologica 2015;59:113–117 DOI: 10.1159/000369855
117
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sions, but visceral involvement is not uncommon. The skeleton is one of the least common sites to be involved by KS, and patients with any clinical and epidemiologic form of KS may manifest with osseous lesions. Skeletal KS lesions typically cause vague bone pain although patients can be asymptomatic. In AIDS-associated KS, osseous lesions are not necessarily a result of direct involvement by mucocutaneous KS, but rather represent disseminated disease. The differential diagnosis of multiple lytic bone lesions is broad and includes, depending on the patient’s demographics, multiple myeloma, metastatic carcinoma and, specifically in HIV-positive patients, bacillary angiomatosis and other infectious processes. FNA cytology is not infrequently the first choice in the diagnostic workup of patients with multiple lytic bone lesions. KS is an important diagnosis to be considered in an HIV-positive patient. Cytologic preparations obtained from KS lesions of the bone have distinct morphology with bland spindle
