CORRESPONDENCE 571

Acknowledgements: This work was supported by grants 6. Li YY, Hanna GJ, Laga AC, et al. Genomic analysis of metastatic cuta-
neous squamous cell carcinoma. Clin Cancer Res 2015; 21: 1447e56.
from National Research Foundation of Korea (2012R1A5A 7. Al-Rohil RN, Tarasen AJ, Carlson JA, et al. Evaluation of 122
2047939, 2017R1E1A1A01074913 and 2017R1A2B2002 advanced-stage cutaneous squamous cell carcinomas by comprehensive
314). genomic profiling opens the door for new routes to targeted therapies.
Cancer 2016; 122: 249e57.
8. Bader AG, Kang S, Vogt PK. Cancer-specific mutations in PIK3CA are
Conflicts of interest and sources of funding: The authors oncogenic in vivo. Proc Natl Acad Sci USA 2006; 103: 1475e9.
state that there are no conflicts of interest to disclose. 9. Jung S-H, Choi YJ, Kim MS, et al. Progression of naive intraepithelial
neoplasia genome to aggressive squamous cell carcinoma genome of
uterine cervix. Oncotarget 2015; 6: 4385e93.
APPENDIX A. SUPPLEMENTARY DATA 10. Kim HS, Lee SE, Bae YS, et al. PIK3CA amplification is asso-
Supplementary data related to this article can be found at ciated with poor prognosis among patients with curatively resected
https://doi.org/10.1016/j.pathol.2018.02.001. esophageal squamous cell carcinoma. Oncotarget 2016; 7: 30691e
701.
11. Yamamoto H, Shigematsu H, Nomura M, et al. PIK3CA mutations and
Su Yeon Yeon1,2,*, Seung Hyun Jung2,3,*, Min copy number gains in human lung cancers. Cancer Res 2008; 68: 6913e
21.
Sung Kim1,2, Yeun-Jun Chung3,4,5, Sug Hyung Lee1,2,3
1 DOI: https://doi.org/10.1016/j.pathol.2018.02.001
Department of Pathology, The Catholic University of
Korea, Seoul, South Korea; 2Cancer Evolution Research
Center, The Catholic University of Korea, Seoul, South
Korea; 3Precision Medicine Research Center, The Catholic
University of Korea, Seoul, South Korea; 4Department of Pilomatrical carcinosarcoma:
Microbiology, The Catholic University of Korea, Seoul, report of a case with comparative
South Korea; 5Integrated Research Center for Genome genomic hybridisation analysis
Polymorphism, The Catholic University of Korea, Seoul,
South Korea; *these authors contributed equally to this work
Sir,
Contact Yeun-Jun Chung. Cutaneous carcinosarcomas are a heterogenous group of
unusual tumours. While the majority include an epithelial
Contact Sug Hyung Lee.
component of ‘epidermal-type’ carcinoma, carcinosarcoma
E-mails: [email protected], [email protected]
with an adnexal epithelial component is well recognised.1 A
limited number of recent studies have shown that, despite the
1. Kowal-Vern A, Criswell BK. Burn scar neoplasms: a literature review
and statistical analysis. Burns 2005; 31: 403e13. striking morphological differences in the appearance of the
2. Huang C-Y, Feng C-H, Hsiao Y-C, et al. Burn scar carcinoma. components, cutaneous carcinosarcomas frequently show
J Dermatol Treat 2010; 21: 350e6. evidence of a clonal origin for both components.2 We report a
3. Nakanishi H, Tomita Y, Yoshikawa H, et al. Frequent p53 gene mu-
tations in soft tissue sarcomas arising in burn scar. Jpn J Cancer Res
case of pilomatrical carcinosarcoma, including array based
1999; 90: 276e9. comparative genomic hybridisation (aCGH) comparing the
4. Hong JH, Jung S-H, Kim MS, et al. Molecular masquerading of rare pilomatrical and sarcomatous components.
EGFR L858M/L861R mutations as common L858R/L861Q mutations
by PNA clamping assay. Pathology 2017; 49: 453e5.
An 87-year-old female presented with a 16 mm nodule on
5. Pickering CR, Zhou JH, Lee JJ, et al. Mutational landscape of aggres- her left hand. Clinically the nodule was dermal and subcu-
sive cutaneous squamous cell carcinoma. Clin Cancer Res 2014; 20: taneous with no surface changes. The patient reported that the
6582e92.

Fig. 1 (A) Scanning view shows a nodular dermally based tumour with biphasic morphology (H&E). (B) One part of the tumour shows matrical differentiation, with
basaloid epithelial cells and abundant shadow cell keratinisation (H&E). (C) Cellular spindled stroma focally surround the pilomatrical component (H&E). (D,E) Part of
the tumour shows sheets of pleomorphic cells resembling an undifferentiated sarcoma admixed with matrical keratin (H&E: D, low power; E, higher power).
572 CORRESPONDENCE Pathology (2018), 50(5), August

lesion had been slowly growing for 4 years. She had previ- The lesion was completely excised and the patient is
ously had several foci of Bowen’s disease from the left cheek, currently well, with no sign of local recurrence or metastases
right upper arm and left forearm removed, with no other at 6 months follow up.
relevant history. Cutaneous carcinosarcoma is an uncommon tumour with
Histopathology of the lesion showed severely sun malignant epithelial and mesenchymal components. Tumours
damaged skin with a dermally based tumour showing in which the epithelial component is of adnexal origin are
biphasic morphology (Fig. 1A). The first area was a rare, though there is some evidence that these lesions are
circumscribed solid and cystic nodule, composed of a pe- associated with a worse prognosis than carcinosarcoma with
ripheral rim of matrical cells surrounding a central zone of a component of ‘epidermal-type’ carcinoma.1 Carcinosar-
matrical keratinisation with numerous ghost cells (Fig. 1B). comas with an ‘epidermal’ component of basal cell carci-
The matrical cells showed mitoses up to 7/mm2, with a pro- noma or squamous cell carcinoma typically arise in sun
liferation index of 20% on MIB1 immunohistochemistry. A damaged skin in the head and neck of elderly patients, with a
foreign body giant cell reaction and focal calcification was clinical presentation similar to that of their carcinomatous
also noted. A small amount of cellular spindled stroma components.4 In comparison, adnexal derived carcinosar-
surrounded this nodule (Fig. 1C). The nodule merged with a coma often occurs in younger patients and may show recent
second area showing an infiltrative edge into the adjacent fat. growth in a long standing nodule.
This area also contained matrical type keratin with ghost Pilomatrixoma, and its rare malignant counterpart malig-
cells, a foreign body giant cell reaction and calcification, nant pilomatrixoma (pilomatrical carcinoma), are tumours
however the cells were predominantly spindled and pleo- showing differentiation toward the hair matrix. Pilomatrical
morphic, many with large bizarre nuclei (Fig. 1D and E). carcinosarcoma as described here, is an exceedingly rare
Mitoses, including atypical forms, were observed (5/mm2) entity, with only three previously reported cases in the liter-
and the proliferation index was 5% on MIB1 staining. A ature.5e7 The criteria for malignancy in pilomatrixoma are
small component of basaloid cells was present attached to the poorly defined and subject to interobserver variability.8,9
undersurface of the epidermis overlying the nodule, archi- While features such as nuclear pleomorphism, frequent and
tecturally resembling a small volume of superficial basal cell atypical mitoses, central necrosis, infiltration of the skin and
carcinoma, but with cytological appearances similar to the soft tissue, and blood and lymphatic invasion are cited as the
pilomatrical component. primary features of concern, in practice this distinction can be
In the area resembling a pilomatrixoma the basaloid cells difficult.10 In this case, as with the previously reported cases
were positive for cytokeratins, including AE1/AE3 and CK5/ by Scholl et al. in 20105 and Hanly et al. in 1994,6 the
6, as well as for beta-catenin, predominantly in a membra- adnexal component did not fulfil clear architectural criteria
nous and cytoplasmic pattern, p63 and p53. The epithelial for malignancy, despite morphological evidence of sarco-
cells were negative for CK7, CK20, CD10, Cam5.2 and matous transformation, and metastasis in one case. In our
BerEP4. The sarcomatoid area was for positive for CD10 and case there was cytological atypia and aCGH showed several
p53, showed focal p63 staining and weak cytoplasmic posi- aberrations in each part of the tumour, with some identical
tivity with beta-catenin, but was negative for a range of other CNVs, supporting the malignant nature of both components,
markers (AE1AE3, CK5/6, CK7, MNF116, CK20, Desmin, and likely common clonal origin. For these reasons we have
and Sox10). designated the lesion pilomatrical carcinosarcoma rather than
CGH was performed on both components of the tumour pilomatricoma with sarcomatous transformation.
separately after microdissection and DNA extraction, The differential diagnosis of these appearances includes a
following a previously described method.3 Several copy collision lesion with components of pilomatrixoma and
number variations (CNVs) were detected in each component, atypical fibroxanthoma (AFX). A collision tumour is defined
with a higher number of CNVs in the sarcomatous compo- as two or more histologically distinct neoplasms coexisting in
nent compared to the epithelial elements (12 versus 5 CNVs, the same anatomical location, with clearly defined bound-
respectively, Fig. 2). The additional CNVs in the sarcomatous aries. While collision of pilomatrixoma and AFX has not
component included homozygous loss of chromosome 9p21 been specifically reported, collision tumours including basal
containing the CDKN2A (p16) gene as well as homozygous cell carcinoma and AFX have been reported twice in the
deletion of chromosome 17q25. There were some identical literature.11 In our case the two areas, while showing distinct
aberrations, including chromosome 9p24.1ep13.2 deletion cell populations, merged in areas with one another, with areas
and chromosome 20p13ep11.1 gain, supporting a common of matrical keratinisation interspersed thorough the sarco-
clonal origin of the two components. matous component. This morphological finding, together

Fig. 2 Array CGH was performed separately on the carcinomatous component (upper) and the sarcomatous component (lower) after microdissection.
 CORRESPONDENCE 573

with the shared chromosomal abnormalities speaks against 12. Harms PW, Fullen DR, Patel RM, et al. Cutaneous basal cell carcino-
sarcomas: evidence of clonality and recurrent chromosomal losses. Hum
the possibility of a collision lesion. Pathol 2015; 46: 690e7.
The presence of multiple CNVs, with some identical copy
changes in the two components, support both the malignant DOI: https://doi.org/10.1016/j.pathol.2018.02.003
character of these components and a likely common clonal
origin. Observation of increasing numbers of CNVs in the
sarcomatous component compared to the matrical elements is
concordant with the interpretation of a more unstable and
distorted genome correlating with a de-differentiated/ Neuroendocrine cells associated
sarcomatous histological phenotype. These findings are with endocrine mucin-producing
concordant with the previous studies on cutaneous basal cell sweat gland carcinoma: a potential
and squamous cell carcinosarcomas, showing a common precursor lesion?
clonal origin in histologically distinct malignant epithelial and
mesenchymal elements based on the detection of similar so-
matic mutations or CNVs in these components.2,12 Deletions of Sir,
chromosome 9p21 harbouring CDKN2A (p16) gene, as seen in Endocrine mucin-producing sweat gland carcinoma
the sarcomatous component here, have previously been re- (EMPSGC) is an under-recognised, extremely rare, low-
ported in cutaneous carcinosarcoma.12 grade cutaneous cancer, with predilection to the eyelid,1e3
In conclusion, we present a rare example of pilomatrical analogous to solid papillary/neuroendocrine ductal carci-
carcinosarcoma, with aCGH evidence of shared cytogenetic noma in situ (NE-DCIS) of the breast.4e6 Recently, we
abnormalities between the epithelial and mesenchymal described the novel developmental concept of widely
components. The mechanisms of sarcomatous trans- distributed NE cells showing isolated/scattered, clustered
formation in cutaneous carcinosarcoma remain unclear, but and/or circumferential emerging patterns in background
loss of CDKN2A function may warrant further study in these mammary tissues of NE-DCIS, representing ‘NE cell hy-
lesions. perplasia’ with premalignant potential.7 Herein, we first
report bland-appearing NE cells that might be related to the
Conflicts of interest and sources of funding: The authors histogenesis of EMPSGC.
state that there are no conflicts of interest to disclose. The patient, a 51-year-old Japanese man, presented with a
left upper eyelid mass which had been present for 4 years. We
Tamazin Leecy, Nima Mesbah Ardakani, Nathan performed an excisional biopsy of this lesion after obtaining
T. Harvey, Benjamin A. Wood informed consent. Histologically, the tumour was composed
of a solid growth of carcinoma cells with a well-developed
PathWest Laboratory Medicine, QEII Medical Centre, vascular network showing a glomeruloid arrangement and/
Nedlands, WA, Australia or hyalinisation (Fig. 1A) and mucin production (Fig. 1B).
Carcinoma cells were polygonal or, occasionally, spindle-
Contact Dr Tamazin Leecy. shaped with finely granular, somewhat eosinophilic cyto-
E-mail: [email protected] plasm and eccentrically-located round to ovoid nuclei
showing a fine-granular chromatin pattern (plasmacytoid
1. Tran TA, Muller S, Chaudahri PJ, et al. Cutaneous carcinosarcoma: appearance). Immunohistochemical examinations revealed
adnexal vs. epidermal types define high-and low-risk tumors. Results of carcinoma cells to be diffusely positive for synaptophysin
a meta-analysis. J Cutan Pathol 2005; 32: 2e11. (Fig. 1C), chromogranin A (Fig. 2A), cytokeratin (CK) 7, ER
2. Paniz-Mondolfi A, Singh R, Jour G, et al. Cutaneous carcinosarcoma:
further insights into its mutational landscape through massive parallel
and PgR (Allred’s total scores: 8 and 8), while being negative
genome sequencing. Virchows Arch 2014; 465: 339e50. for CK5/6 and CK20. The Ki-67 (MIB-1) labelling index was
3. Ardakani NM, Thomas C, Robinson C, et al. Detection of copy number 12.2%. Myoepithelial cells reactive for CK5/6 and p40 were
variations in melanocytic lesions utilising array based comparative identified along the periphery of carcinoma cell nests as well
genomic hybridisation. Pathology 2017; 49: 285e91.
4. Harvey NT, Sinha A, Houghton DC, et al. Basal cell carcinosarcoma: a as on concomitant fibrovascular cores.
report of 4 cases and review of the literature. Am J Dermatopathol 2014; Intriguingly, we noted non-neoplastic-looking NE cells
36: 483e9. demonstrating chromogranin A in the sweat ducts (Fig. 2).
5. Scholl P, Snyder N, Patt D, et al. Pilomatrical carcinosarcoma.
Otolaryngol Head Neck Surg 2010; 143: S36e7. Careful observation using serial sections, with immunohis-
6. Hanly M, Allsbrook W, Pantazis C, et al. Pilomatrical carcinosarcoma tochemical and H&E staining, revealed that these small NE
of the cheek with subsequent pulmonary metastases: a case report. Am J cells were polygonal with slightly eosinophilic, fine-
Dermatopathol 1994; 16: 196e200.
7. Suyama T, Momose S, Yokoyama M, et al. Pilomatrical carcinosarcoma
granular cytoplasm and ovoid nuclei without atypism
of the cheek: immunohistochemical and molecular analysis of beta- (Fig. 2B,C).
catenin. Pathol Int 2017; 67: 324e6. It is well known that NE cells are extensively distributed
8. Sassmannshausen J, Chaffins M. Pilomatrix carcinoma: a report of a not only in endocrine but also in non-endocrine organs, such
case arising from a previously excised pilomatrixoma and a review of
the literature. J Am Acad Dermatol 2001; 44: 358e61. as the gastrointestinal and respiratory systems.8 As for the
9. van der Walt JD, Rohlova B. Carcinomatous transformation in a pilo- skin, Merkel cells are generally present in basal layers of the
matrixoma. Am J Dermatopathol 1984; 6: 63e70. epidermis and in some instances, in the eccrine ridges or
10. O’donovan D, Freemont A, Adams J, et al. Malignant pilomatrixoma
with bone metastasis. Histopathology 1993; 23: 385e6.
ducts, and may be the developmental origin of Merkel cell
11. Speiser JJ, Aggarwal S, Wold L, et al. A rare collision in dermatopa- carcinoma.9,10 However, in the current case, we failed to
thology: basal cell carcinoma and atypical fibroxanthoma. Am J demonstrate the presence of Merkel cells using anti-CK20
Dermatopathol 2015; 37: 950. immunohistochemistry in orbital sweat gland apparatus,
and EMPSGC itself was also consistently negative for this