© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
J Cutan Pathol 2014: 41: 45–50 doi: 10.1111/cup.12250 John Wiley & Sons. Printed in Singapore
Journal of Cutaneous Pathology
Multiple lesions of granular cell basal cell carcinoma: a case report Granular cell change in basal cell carcinoma (BCC) occurs rarely. Only 11 such cases have been reported; all of them were solitary nodular BCC. We report herein a case of multiple granular cell BCC with infundibulocystic features. The tumors presented as papules on the anterior neck of a 44-year-old female with a prior history of a well-differentiated squamous cell carcinoma (SCC) of the tongue and radiation involving the area in which BCC developed. Microscopically, the tumors were circumscribed small dermal nodules composed of epithelial cords with granular eosinophilic cytoplasm and entrapped infundibular keratocysts. Given the eosinophilic appearance of the tumor, history of SCC and the lesions multiplicity, the initial biopsy was first interpreted as metastatic SCC. The correct diagnosis of granular cell BCC was established upon rereview of the slides at a cancer center. Given the diagnostic controversy, immunohistochemical stains were performed. The tumor cells expressed Ber-EP4, CD63 (NKI/C3) and CD68. The tumors were compared to the prior SCC finding different morphologies. Extensive clinical evaluation showed no evidence of recurrent SCC. This report expands the clinicopathologic spectrum of granular cell variant of BCC and documents for the first time eruption of multiple such tumors in a localized area. Keywords: basal cell, granular cell change, infundibulocystic features Jedrych J, Busam KJ. Multiple lesions of granular cell basal cell carcinoma: a case report. J Cutan Pathol 2014; 41: 45–50. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Basal cell carcinoma (BCC) represents a commonly encountered tumor in the daily practice of a dermatopathology laboratory.1 Its diagnosis is usually straightforward. Diagnostic difficulties tend to be related to small tissue samples revealing only rare tumor cells, unusual morphologic features, such as prominent squamous differentiation or clear cell changes or unexpected immunohistochemical findings, such as labeling for chromogranin. Granular cell cytoplasmic change is a very unusual morphologic feature that may also lead to diagnostic confusion. It is exceedingly rare in BCC, with merely 11 such cases previously described in the literature.2 – 11 Herein, we present a previously unreported occurrence of multiple granular cell BCC with infundibulocystic features.
Jaroslaw Jedrych† and Klaus J. Busam Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA † Present address: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Klaus J Busam, MD Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA Tel: +1 212 639 5679 Fax: +1 212 714 6224 e-mail: [email protected] Accepted for publication October 10, 2013
Case report Clinical findings A 44-year-old female had a history of hypothyroidism and well-differentiated squamous cell carcinoma (SCC) of the tongue with metastases to the neck lymph nodes. She had been treated with a partial glossectomy, radical neck dissection and local radiotherapy 17 years prior to the current presentation. She was presented to her dermatologist with multiple tan colored papules measuring 2 to 4 mm in greatest dimension involving her right, anterior and left neck – in the area corresponding to the prior radiation field (Fig. 1). The lesions had been present and stable for a few years; however, the patient was seeking medical counseling and removal for cosmetic
45
Jedrych & Busam membrane, rare pseudoinclusions and inconspicuous nucleoli. Nuclei were eccentrically placed in fair amounts of finely and diffusely granular eosinophilic cytoplasm. Focally, coarser oval to round cytoplasmic globoid inclusions were noted, sporadically indenting the nuclear surface. Granular cytoplasmic change was present uniformly throughout the neoplastic epithelium with no co-occurrence of other cell types. Rare mitotic figures and apoptotic bodies were noted. Immunohistochemical staining showed expression of CD63 (NK1/C3 clone), Ber-EP4 (Fig. 3) and CD68 (KP1 clone) (Fig. 4). Fig. 1. Granular cell basal cell carcinoma with infundibulocystic features: clinical findings. Multiple tan colored follicular-based papules are present on the anterior neck (arrows).
reasons. A biopsy of a single papule of the right neck was performed and was submitted to a dermatopathology laboratory, where an experienced dermatopathologist reported the findings as metastatic SCC. The patient was referred to a cancer center for further evaluation. Detailed physical examination and imaging studies showed no evidence of metastatic disease. A reexcision of the skin of the right neck and a biopsy of an additional lesion from the left neck were performed. The initial right neck biopsy was retrospectively reviewed. The patient was followed for skin surveillance and observation of the remaining lesions. No evidence of disease progression was noted in a follow-up period of 12 months. Histopathologic findings Review of the slide, which was initially reported as metastatic SCC, revealed an eosinophilic dermal nodule composed of interconnecting epithelial strands with scattered keratocysts (Fig. 2). The reexcision at this site showed additional six small dermal tumors with similar histomorphological features. In each case, the overlying epidermis was unremarkable. Each tumor was composed of interconnecting buds, nests and cords comprised of small polygonal cells forming vaguely developed palisade at the periphery (Figs. 3 and 4). Retractions at the epithelial–stromal interface were evident, and such spaces occasionally contained small amounts of mucin. Depending on the tumor size, one or more keratotic cysts containing brightly eosinophilic laminated keratin were present within the lesional epithelium. Occasional connection to the epidermis or adjacent follicular infundibulum was seen. Cytologically, tumor cells showed small, round to oval relatively monomorphic nuclei with finely dispersed chromatin, smooth nuclear
46
Discussion Granular cell change is not specific for any particular cell type. Rather, the phenomenon reflects the accumulation of secondary lysosomes within cell cytoplasm.4,12 The lysosomes account for immunoreactivity for CD68. The prototypical dermal neoplasm with granular cell features is the so-called granular cell tumor, which because of its expression of S100 protein is thought to be of Schwann cell lineage.12 Granular cell features, however, have been reported in many different tumor types, including leiomyoma, leiomyosarcoma, atypical fibroxanthoma, angiofibroma, dermatofibroma, dermatofibrosarcoma protuberans, melanoma, non-neural granular cell tumor (primitive polypoid granular cell tumor), angiosarcoma and BCC.5,6,10,13 The clinical and histopathologic features of previously reported cases of granular cell BCC are summarized in Tables 1 and 2, respectively, and parallel those of conventional BCC.1 Tumors were found in elderly patients (mean age at diagnosis: 61.6 years) with a male predominance (M : F ratio 3 : 1), and occurred on the head and neck (83% of cases) and trunk. All previously described granular cell BCC were solitary nodular tumors. The vast majority of the patients were treated surgically with no evidence of recurrence with a mean follow up of 13.9 months. The aggregated data suggest that the clinical course was indolent and not different than outcomes of usual BCC; therefore, there is no prognostic significance to the granular cell phenotype. Its main relevance lies in the potential to be confused with other tumors, as it happened in the case reported herein – the granular cell variant of BCC with infundibulocystic features was misdiagnosed as metastatic SCC. Of note, although co-occurrence of granular cell tumor and conventional SCC has been reported,14 the authors are not aware of any description of SCC with granular cell change. Ultrastructural studies were performed on five previously reported tumors.2 – 6 In all cases, abundant
Granular basal cell carcinoma
Fig. 2. Granular cell basal cell carcinoma with infundibulocystic features. A) Scanning magnification of a dermal eosinophilic nodule with small keratocysts (hematoxylin/eosin, ×40). B) The tumor cells show finely granular eosinophilic cytoplasm (hematoxylin/eosin, ×400).
Fig. 3. Granular basal cell carcinoma with infundibulocystic features. A) Low power view shows a dermal tumor composed of eosinophilic strands with keratotic cyst (hematoxylin/eosin, ×40). B) Retractions at the epithelial–stromal interface are evident, occasionally containing small amounts of mucin (hematoxylin/eosin, ×100). C) Tumors were composed solely of granular cells. Peripheral cell palisade typical for basal cell carcinoma was effaced in this example (hematoxylin/eosin, ×200). D) Immunohistochemical staining shows expression of Ber-EP4 (×40). E) Tumor is immunoreactive for CD63 (NK1/C3 clone) (×40).
cytoplasmic lysosome-like granules were revealed, similar to those seen in conventional granular cell tumor, but angulated bodies, characteristic for the latter,2 were absent. The vesicles responsible for morphologic change of the cytoplasm had ultrastructural features of lysosomes and represent either true lysosomes or infoldings of the cytoplasmic membrane subsequently phagocytosed and digested
by lysosomes.5,6,15 Expression of CD68 (KP1 clone), a glycoprotein epitope associated with lysosomal membranes,10 was documented by immunohistochemical studies in one previously reported tumor.11 Multiple granular BCC have not been previously described. Because the tumor was initially not recognized as BCC, the multiplicity of tumors confounded the diagnostic error; in the context of the patient’s
47
Jedrych & Busam
Fig. 4. Granular basal cell carcinoma with infundibulocystic features. A) Low magnification displays tumor connection to the epidermis (hematoxylin/eosin, ×40). B) Immunohistochemical staining shows expression of CD68 KP1 clone (×40). Table 1. Clinical and follow-up information regarding reported patients with granular cell basal cell carcinoma Reference
Age (years)/sex
Barr and Graham2 Patient 1 Patient 2 Mrak and Baker3 LeBoit et al.4 García Prats et al.5 Boscaino et al.6 Reichel7 Hayden and Shamma8 Myung et al.9 Dundr et al.10 Kanitakis and Chouvet11 Current case
72/M ‘Elderly’/M 67/M 30/F 67/M 81/M 50/M 65/M 62/M 69/F 71/M 44/F
Site/size (cm)
Duration (years)
Treatment
Follow up (months)
Nose/0.7 Face/1.3 Supraclavicular/NC Lower eyelid/NC Nose/1 Nose/1.1 Chest/1 Cheek/NC Chest/1 Nose/1 Face/NC Neck/0.2–0.4
1 NC 2* NC Several Several NC NC 5 2 NC** Several
Desiccation Excision Excision Shave removal Excision Excision Excision Desiccation Excision Excision NC Excision
4/NR NC NC 30/NR 2/NR 24/NR 24/NR NC 12/NR 9/NR NC 12/NR
NC, not communicated; NR, no recurrence; M, male; F, female. *The patient was initially treated with local radiation therapy; tumor recurred 12 year after the initial treatment. **Tumor presented at the site of previously excised basal cell carcinoma.
prior history of tongue cancer, the dermatopathologist interpreted the skin lesion(s) as metastatic SCC. The tumors reported herein, however, were not metastases and were different from conventional well-differentiated SCC by virtue of their granular cytoplasm, relatively bland cytomorphology and low mitotic index. Upon reevaluation, the tumors were interpreted as BCC with infundibulocystic features due to the presence of small follicular keratocysts, retiform epithelial strands, stroma-epithelial retraction and focal mucinous stroma. Furthermore, the tumor cells were found to express Ber-EP4 antigen, as is typical of BCC. The granular cell features were apparent as numerous small, fine, eosinophilic cytoplasmic granules on routine hematoxylin and eosin-stained sections and confirmed by immunoreactivity for CD63 (NKI/C3 clone) and CD68 (KP1 clone). In our patient, the tumors were confined to an area previously exposed to radiotherapy, suggesting a possibility of radiation-induced oncogenesis. A
48
case of granular BCC associated with radiotherapy has been previously reported by Mrak and Baker.3 Exposure to ionizing radiation has been linked with an increased occurrence of BCC.1 In a population-based case-control study, relative risk of BCC development at the site of prior therapy was 3.3 among irradiated individuals.16 The risk of developing non-melanocytic skin cancer appears to increase with time from the exposure,17 and peaks in patients treated 40 years or longer before the diagnosis.16 In a study evaluating skin cancer risk in patients treated with radiation before 20 years of age, all detected BCC were confined within the radiation field implying a crucial role of radiotherapy in developing these tumors even without significant contribution of ultraviolet light.18 Patients with nevoid BCC (Gorlin) syndrome are especially sensitive to ionizing radiation and prone to develop multiple BCC in the radiation field.19 In addition, some authors described the occurrence of infundibulocystic BCC in patients with this syndrome.20 Although the occurrence of
Nodular
Nodular
Nodular
Nodular
Nodular
Nodular Nodular
Nodular
Nodular
Nodular
Infindibulocystic
Barr and Graham2 Patient 1 Patient 2
Mrak and Baker3
LeBoit et al.4
García Prats et al.5
Boscaino et al.6
Reichel7 Hayden and Shamma8
Myung et al.9
Dundr et al.10
Kanitakis and Chouvet11
Current case
Exclusive cell type
Comprising center of nodules; basaloid cells palisade at the periphery Sheet emanating from tumor base Nodules with basaloid palisade and granular center separate from nodules uniformly composed of granular cells Comprising center of nodules; basaloid cells palisade at the periphery Comprising center of nodules; basaloid cells palisade at the periphery Vast majority
Comprising center of nodules; basaloid cells palisade at the periphery
Focal
Comprising center of nodules; basaloid cells palisade at the periphery Exclusive cell type
Distribution of granular cells
NP, not performed; BCC, CK, cytokeratin; HPF, high power microscopic field.
Pattern
Reference
Fibrotic
Fibroelastotic
Fibroplastic
Fibrotic
Myxoid Mucinous
Fibromatoid
Sclerotic
Myxoid
Desmoplastic
Myxoid
Stroma
Table 2. Primary histopathologic features of reported patients with granular cell basal cell carcinoma
None
None
None None
None
1–5/10 HPF
Frequent
+/+
+/NC
+/+ +/+
+/+
+/+
+/+
Rare
Rare
+/+
Focal/+
None
None
Mitotic figures
Focal/+
+/+
Palisading/ clefting
Positive for BER-EP4, AE1/AE3 and Cam5.2(focal weak); negative for CD68(KP1); Ki67 25–29% Positive for AE1/AE3, CD68(KP1 and PGM1)(15%), CD15, bcl2, p63, vimentin (
J Cutan Pathol 2014: 41: 45–50 doi: 10.1111/cup.12250 John Wiley & Sons. Printed in Singapore
Journal of Cutaneous Pathology
Multiple lesions of granular cell basal cell carcinoma: a case report Granular cell change in basal cell carcinoma (BCC) occurs rarely. Only 11 such cases have been reported; all of them were solitary nodular BCC. We report herein a case of multiple granular cell BCC with infundibulocystic features. The tumors presented as papules on the anterior neck of a 44-year-old female with a prior history of a well-differentiated squamous cell carcinoma (SCC) of the tongue and radiation involving the area in which BCC developed. Microscopically, the tumors were circumscribed small dermal nodules composed of epithelial cords with granular eosinophilic cytoplasm and entrapped infundibular keratocysts. Given the eosinophilic appearance of the tumor, history of SCC and the lesions multiplicity, the initial biopsy was first interpreted as metastatic SCC. The correct diagnosis of granular cell BCC was established upon rereview of the slides at a cancer center. Given the diagnostic controversy, immunohistochemical stains were performed. The tumor cells expressed Ber-EP4, CD63 (NKI/C3) and CD68. The tumors were compared to the prior SCC finding different morphologies. Extensive clinical evaluation showed no evidence of recurrent SCC. This report expands the clinicopathologic spectrum of granular cell variant of BCC and documents for the first time eruption of multiple such tumors in a localized area. Keywords: basal cell, granular cell change, infundibulocystic features Jedrych J, Busam KJ. Multiple lesions of granular cell basal cell carcinoma: a case report. J Cutan Pathol 2014; 41: 45–50. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Basal cell carcinoma (BCC) represents a commonly encountered tumor in the daily practice of a dermatopathology laboratory.1 Its diagnosis is usually straightforward. Diagnostic difficulties tend to be related to small tissue samples revealing only rare tumor cells, unusual morphologic features, such as prominent squamous differentiation or clear cell changes or unexpected immunohistochemical findings, such as labeling for chromogranin. Granular cell cytoplasmic change is a very unusual morphologic feature that may also lead to diagnostic confusion. It is exceedingly rare in BCC, with merely 11 such cases previously described in the literature.2 – 11 Herein, we present a previously unreported occurrence of multiple granular cell BCC with infundibulocystic features.
Jaroslaw Jedrych† and Klaus J. Busam Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA † Present address: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Klaus J Busam, MD Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA Tel: +1 212 639 5679 Fax: +1 212 714 6224 e-mail: [email protected] Accepted for publication October 10, 2013
Case report Clinical findings A 44-year-old female had a history of hypothyroidism and well-differentiated squamous cell carcinoma (SCC) of the tongue with metastases to the neck lymph nodes. She had been treated with a partial glossectomy, radical neck dissection and local radiotherapy 17 years prior to the current presentation. She was presented to her dermatologist with multiple tan colored papules measuring 2 to 4 mm in greatest dimension involving her right, anterior and left neck – in the area corresponding to the prior radiation field (Fig. 1). The lesions had been present and stable for a few years; however, the patient was seeking medical counseling and removal for cosmetic
45
Jedrych & Busam membrane, rare pseudoinclusions and inconspicuous nucleoli. Nuclei were eccentrically placed in fair amounts of finely and diffusely granular eosinophilic cytoplasm. Focally, coarser oval to round cytoplasmic globoid inclusions were noted, sporadically indenting the nuclear surface. Granular cytoplasmic change was present uniformly throughout the neoplastic epithelium with no co-occurrence of other cell types. Rare mitotic figures and apoptotic bodies were noted. Immunohistochemical staining showed expression of CD63 (NK1/C3 clone), Ber-EP4 (Fig. 3) and CD68 (KP1 clone) (Fig. 4). Fig. 1. Granular cell basal cell carcinoma with infundibulocystic features: clinical findings. Multiple tan colored follicular-based papules are present on the anterior neck (arrows).
reasons. A biopsy of a single papule of the right neck was performed and was submitted to a dermatopathology laboratory, where an experienced dermatopathologist reported the findings as metastatic SCC. The patient was referred to a cancer center for further evaluation. Detailed physical examination and imaging studies showed no evidence of metastatic disease. A reexcision of the skin of the right neck and a biopsy of an additional lesion from the left neck were performed. The initial right neck biopsy was retrospectively reviewed. The patient was followed for skin surveillance and observation of the remaining lesions. No evidence of disease progression was noted in a follow-up period of 12 months. Histopathologic findings Review of the slide, which was initially reported as metastatic SCC, revealed an eosinophilic dermal nodule composed of interconnecting epithelial strands with scattered keratocysts (Fig. 2). The reexcision at this site showed additional six small dermal tumors with similar histomorphological features. In each case, the overlying epidermis was unremarkable. Each tumor was composed of interconnecting buds, nests and cords comprised of small polygonal cells forming vaguely developed palisade at the periphery (Figs. 3 and 4). Retractions at the epithelial–stromal interface were evident, and such spaces occasionally contained small amounts of mucin. Depending on the tumor size, one or more keratotic cysts containing brightly eosinophilic laminated keratin were present within the lesional epithelium. Occasional connection to the epidermis or adjacent follicular infundibulum was seen. Cytologically, tumor cells showed small, round to oval relatively monomorphic nuclei with finely dispersed chromatin, smooth nuclear
46
Discussion Granular cell change is not specific for any particular cell type. Rather, the phenomenon reflects the accumulation of secondary lysosomes within cell cytoplasm.4,12 The lysosomes account for immunoreactivity for CD68. The prototypical dermal neoplasm with granular cell features is the so-called granular cell tumor, which because of its expression of S100 protein is thought to be of Schwann cell lineage.12 Granular cell features, however, have been reported in many different tumor types, including leiomyoma, leiomyosarcoma, atypical fibroxanthoma, angiofibroma, dermatofibroma, dermatofibrosarcoma protuberans, melanoma, non-neural granular cell tumor (primitive polypoid granular cell tumor), angiosarcoma and BCC.5,6,10,13 The clinical and histopathologic features of previously reported cases of granular cell BCC are summarized in Tables 1 and 2, respectively, and parallel those of conventional BCC.1 Tumors were found in elderly patients (mean age at diagnosis: 61.6 years) with a male predominance (M : F ratio 3 : 1), and occurred on the head and neck (83% of cases) and trunk. All previously described granular cell BCC were solitary nodular tumors. The vast majority of the patients were treated surgically with no evidence of recurrence with a mean follow up of 13.9 months. The aggregated data suggest that the clinical course was indolent and not different than outcomes of usual BCC; therefore, there is no prognostic significance to the granular cell phenotype. Its main relevance lies in the potential to be confused with other tumors, as it happened in the case reported herein – the granular cell variant of BCC with infundibulocystic features was misdiagnosed as metastatic SCC. Of note, although co-occurrence of granular cell tumor and conventional SCC has been reported,14 the authors are not aware of any description of SCC with granular cell change. Ultrastructural studies were performed on five previously reported tumors.2 – 6 In all cases, abundant
Granular basal cell carcinoma
Fig. 2. Granular cell basal cell carcinoma with infundibulocystic features. A) Scanning magnification of a dermal eosinophilic nodule with small keratocysts (hematoxylin/eosin, ×40). B) The tumor cells show finely granular eosinophilic cytoplasm (hematoxylin/eosin, ×400).
Fig. 3. Granular basal cell carcinoma with infundibulocystic features. A) Low power view shows a dermal tumor composed of eosinophilic strands with keratotic cyst (hematoxylin/eosin, ×40). B) Retractions at the epithelial–stromal interface are evident, occasionally containing small amounts of mucin (hematoxylin/eosin, ×100). C) Tumors were composed solely of granular cells. Peripheral cell palisade typical for basal cell carcinoma was effaced in this example (hematoxylin/eosin, ×200). D) Immunohistochemical staining shows expression of Ber-EP4 (×40). E) Tumor is immunoreactive for CD63 (NK1/C3 clone) (×40).
cytoplasmic lysosome-like granules were revealed, similar to those seen in conventional granular cell tumor, but angulated bodies, characteristic for the latter,2 were absent. The vesicles responsible for morphologic change of the cytoplasm had ultrastructural features of lysosomes and represent either true lysosomes or infoldings of the cytoplasmic membrane subsequently phagocytosed and digested
by lysosomes.5,6,15 Expression of CD68 (KP1 clone), a glycoprotein epitope associated with lysosomal membranes,10 was documented by immunohistochemical studies in one previously reported tumor.11 Multiple granular BCC have not been previously described. Because the tumor was initially not recognized as BCC, the multiplicity of tumors confounded the diagnostic error; in the context of the patient’s
47
Jedrych & Busam
Fig. 4. Granular basal cell carcinoma with infundibulocystic features. A) Low magnification displays tumor connection to the epidermis (hematoxylin/eosin, ×40). B) Immunohistochemical staining shows expression of CD68 KP1 clone (×40). Table 1. Clinical and follow-up information regarding reported patients with granular cell basal cell carcinoma Reference
Age (years)/sex
Barr and Graham2 Patient 1 Patient 2 Mrak and Baker3 LeBoit et al.4 García Prats et al.5 Boscaino et al.6 Reichel7 Hayden and Shamma8 Myung et al.9 Dundr et al.10 Kanitakis and Chouvet11 Current case
72/M ‘Elderly’/M 67/M 30/F 67/M 81/M 50/M 65/M 62/M 69/F 71/M 44/F
Site/size (cm)
Duration (years)
Treatment
Follow up (months)
Nose/0.7 Face/1.3 Supraclavicular/NC Lower eyelid/NC Nose/1 Nose/1.1 Chest/1 Cheek/NC Chest/1 Nose/1 Face/NC Neck/0.2–0.4
1 NC 2* NC Several Several NC NC 5 2 NC** Several
Desiccation Excision Excision Shave removal Excision Excision Excision Desiccation Excision Excision NC Excision
4/NR NC NC 30/NR 2/NR 24/NR 24/NR NC 12/NR 9/NR NC 12/NR
NC, not communicated; NR, no recurrence; M, male; F, female. *The patient was initially treated with local radiation therapy; tumor recurred 12 year after the initial treatment. **Tumor presented at the site of previously excised basal cell carcinoma.
prior history of tongue cancer, the dermatopathologist interpreted the skin lesion(s) as metastatic SCC. The tumors reported herein, however, were not metastases and were different from conventional well-differentiated SCC by virtue of their granular cytoplasm, relatively bland cytomorphology and low mitotic index. Upon reevaluation, the tumors were interpreted as BCC with infundibulocystic features due to the presence of small follicular keratocysts, retiform epithelial strands, stroma-epithelial retraction and focal mucinous stroma. Furthermore, the tumor cells were found to express Ber-EP4 antigen, as is typical of BCC. The granular cell features were apparent as numerous small, fine, eosinophilic cytoplasmic granules on routine hematoxylin and eosin-stained sections and confirmed by immunoreactivity for CD63 (NKI/C3 clone) and CD68 (KP1 clone). In our patient, the tumors were confined to an area previously exposed to radiotherapy, suggesting a possibility of radiation-induced oncogenesis. A
48
case of granular BCC associated with radiotherapy has been previously reported by Mrak and Baker.3 Exposure to ionizing radiation has been linked with an increased occurrence of BCC.1 In a population-based case-control study, relative risk of BCC development at the site of prior therapy was 3.3 among irradiated individuals.16 The risk of developing non-melanocytic skin cancer appears to increase with time from the exposure,17 and peaks in patients treated 40 years or longer before the diagnosis.16 In a study evaluating skin cancer risk in patients treated with radiation before 20 years of age, all detected BCC were confined within the radiation field implying a crucial role of radiotherapy in developing these tumors even without significant contribution of ultraviolet light.18 Patients with nevoid BCC (Gorlin) syndrome are especially sensitive to ionizing radiation and prone to develop multiple BCC in the radiation field.19 In addition, some authors described the occurrence of infundibulocystic BCC in patients with this syndrome.20 Although the occurrence of
Nodular
Nodular
Nodular
Nodular
Nodular
Nodular Nodular
Nodular
Nodular
Nodular
Infindibulocystic
Barr and Graham2 Patient 1 Patient 2
Mrak and Baker3
LeBoit et al.4
García Prats et al.5
Boscaino et al.6
Reichel7 Hayden and Shamma8
Myung et al.9
Dundr et al.10
Kanitakis and Chouvet11
Current case
Exclusive cell type
Comprising center of nodules; basaloid cells palisade at the periphery Sheet emanating from tumor base Nodules with basaloid palisade and granular center separate from nodules uniformly composed of granular cells Comprising center of nodules; basaloid cells palisade at the periphery Comprising center of nodules; basaloid cells palisade at the periphery Vast majority
Comprising center of nodules; basaloid cells palisade at the periphery
Focal
Comprising center of nodules; basaloid cells palisade at the periphery Exclusive cell type
Distribution of granular cells
NP, not performed; BCC, CK, cytokeratin; HPF, high power microscopic field.
Pattern
Reference
Fibrotic
Fibroelastotic
Fibroplastic
Fibrotic
Myxoid Mucinous
Fibromatoid
Sclerotic
Myxoid
Desmoplastic
Myxoid
Stroma
Table 2. Primary histopathologic features of reported patients with granular cell basal cell carcinoma
None
None
None None
None
1–5/10 HPF
Frequent
+/+
+/NC
+/+ +/+
+/+
+/+
+/+
Rare
Rare
+/+
Focal/+
None
None
Mitotic figures
Focal/+
+/+
Palisading/ clefting
Positive for BER-EP4, AE1/AE3 and Cam5.2(focal weak); negative for CD68(KP1); Ki67 25–29% Positive for AE1/AE3, CD68(KP1 and PGM1)(15%), CD15, bcl2, p63, vimentin (
