Letters to the Editor
REFERENCES 1 Robson A, Greene J, Ansari N et al. Eccrine porocarcinoma (malignant eccrine poroma): a clinicopathologic study of 69 cases. Am J Surg Pathol 2001; 25: 710–720. 2 De Iuliis F, Amoroso L, Taglieri L et al. Chemotherapy of rare skin adnexal tumors: a review of literature. Anticancer Res 2014; 34: 5263–5268. 3 Plunkett TA, Hanby AM, Miles DW, Rubens RD. Metastatic eccrine porocarcinoma: response to docetaxel (Taxotere) chemotherapy. Ann Oncol 2001; 12: 411–414.
4 O’Neill VJ, Kaye SB, Reed NS, Paul J, Davis JA, Vasey PA. A dosefinding study of carboplatin-epirubicin-docetaxel in advanced epithelial ovarian cancer. Br J Cancer 2002; 86: 1385–1390. 5 Rossi A, Di Maio M, Chiodini P et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol 2012; 30: 1692–1698.
Cutaneous squamous cell carcinoma with extensive perineural invasion and perineural cyst formation without regional lymph node metastases Dear Editor, A new staging system for cutaneous squamous cell carcinoma (cSCC) was recently adopted by the American Joint Committee
(a)
on Cancer, in which perineural invasion (PNI) was newly added as a high-risk characteristic.1 Regional lymph node (LN) and distant metastases occur significantly more frequently in cSCC
(d) (g)
(b) (e)
(h)
(f)
(i)
(c)
Figure 1. (a) An exophytic, papillomatous, keratotic tumor measuring 16 cm 9 6 cm with central ulceration in the right popliteal fossa. (b) The excised tumor showed the enlarged nerve trunk extending centrally (black arrows). The section cut along the blue line is shown in (c). (c) Histopathology of the excised tumor and the nerve trunk showing infiltrative nests of atypical keratinocytes arising from the epidermis. Within and around the nerve, cysts mimicking epidermal cysts were formed. The panoramic photo showing the whole image of the band-like structure was created by stitching five overlapping photos (hematoxylin–eosin). (d) A peripheral nerve was invaded by tumor cells. Arrows indicate intraneural island of tumor cells (hematoxylin–eosin). (e) A nest of tumor cells was present inside the nerve (hematoxylin–eosin). (f) Immunohistochemical stain of (e) demonstrated nerve bundles (S-100 stain). (g) The cysts were lined by a stratified squamous epithelium and filled with keratin. Nerve tissues (blue circle) surrounded the cysts (hematoxylin–eosin). (h) Intraneural island of tumor cells in the nerve tissue near right inguinal LN (hematoxylin–eosin). (i) Immunohistochemical stain of (h) demonstrated nerve bundles (S-100 stain).
Correspondence: Fumi Miyagawa, M.D., Ph.D., Department of Dermatology, Nara Medical University School of Medicine, 840 Shijo, Kashihara, Nara 634-8522, Japan. Email: [email protected]
930
© 2015 Japanese Dermatological Association
Letters to the Editor
with PNI than in cSCC without PNI.2 We report a case of cSCC in which gross involvement of a large-caliber nerve was observed, but not metastatic spread to regional LN. We also found an intraneural cyst mimicking an epidermal cyst covering almost the entire nerve trunk. An 84-year-old man had noted a tumor in the right popliteal fossa 6 months previously. He experienced paresthesia in the right popliteal fossa during the 6 months, which had become painful 2 months prior to admission. A physical examination revealed a reddish, papillomatous tumor (Fig. 1a). Positron emission tomography and computed tomography showed no evidence of nodal and distant metastases. The tumor was excised. Intraoperatively, there was a firm, thick band-like structure running parallel with the great saphenous vein, originating from the tumor and extending centrally toward the inguinal region (Fig. 1b). Neural invasion involving the posterior femoral cutaneous nerve was suspected. The band-like structure was cut off at the middle of the thigh and he subsequently underwent sentinel LN dissection. Histopathology showed invading strands of atypical keratinocytes within the dermis and subcutis. In the subcutis, cystic space filled with keratin had formed within the enlarged nerve over a long distance, where no tumor was present in most areas (Fig. 1c). In some areas, tumor cells invaded the nerve and formed intraneural nests (Fig. 1d–f). It was also observed that cystic structures were partially surrounded by nerve tissues (Fig. 1g). No tumor cells were found in a right inguinal LN specimen. The nerve tissue near right inguinal LN taken during the sentinel LN dissection demonstrated an intraneural island of atypical keratinocytes (Fig. 1h,i), suggesting PNI over a long distance from the popliteal fossa to the inguinal region. Although postoperative radiotherapy was planned, he died from aspiration pneumonia while he was being temporarily discharged from the hospital. Perineural invasion is a form of spread of malignant tumors by growth in and around a nerve2,3 and has been estimated to occur in 2.5–14% of cSCC.3 Patients with PNI sometimes exhibit neurological symptoms, including pain, paresthesia and loss
of motor skills,2,4 as happened in our patient. Recent studies have shown that large-caliber PNI is associated with a 4–5-fold increased risk of nodal metastases and death compared with small-caliber PNI.5 However, despite the fact that the tumor cells invaded a large-caliber nerve and spread perineurally over a long distance, our patient did not have regional LN metastases. An interesting finding in our case is that a cyst was present over most of the area of the nerve involved. Because we did not find cysts in the primary lesion, the tumor cells within perineural tissue are likely to re-differentiate toward more differentiated SCC, which predisposed the PNI lesion to form a cyst.
CONFLICT OF INTEREST:
None.
Fumi MIYAGAWA,1 Chiharu HIROSE,1 Takaya FUKUMOTO,1 Hideki ASAI,2 Nobuhiko KOBAYASHI,1 Hideo ASADA1 1
Department of Dermatology, and 2The Center for Plastic Surgery, Nara Medical University School of Medicine, Nara, Japan doi: 10.1111/1346-8138.12981
REFERENCES 1 Farasat S, Yu SS, Neel VA et al. A new American Joint Committee on Cancer staging system for cutaneous squamous cell carcinoma: creation and rationale for inclusion of tumor (T) characteristics. J Am Acad Dermatol 2011; 64: 1051–1059. 2 Goepfert H, Dichtel WJ, Medina JE, Lindberg RD, Luna MD. Perineural invasion in squamous cell skin carcinoma of the head and neck. Am J Surg 1984; 148: 542–547. 3 Leibovitch I, Huilgol SC, Selva D, Hill D, Richards S, Paver R. Cutaneous squamous cell carcinoma treated with Mohs micrographic surgery in Australia II. Perineural invasion. J Am Acad Dermatol 2005; 53: 261–266. 4 Cottel WI. Perineural invasion by squamous-cell carcinoma. J Dermatol Surg Oncol 1982; 8: 589–600. 5 Carter JB, Johnson MM, Chua TL, Karia PS, Schmults CD. Outcomes of primary cutaneous squamous cell carcinoma with perineural invasion: an 11-year cohort study. JAMA Dermatol 2013; 149: 35–41.
Multiple eruptive milia and milia en plaque on the hands and feet of a 2-month-old female Dear Editor, A 2-month-old female presented with multiple papules on both hands and feet. One week earlier, white papules and erythematous plaques studded with white papules had developed on both acral areas and then spread. The patient’s history was unremarkable; there was no history of trauma, including friction or rubbing, sunlight exposure, topical use of medical ointments or drug intake before the development of the skin lesions. Also, her
family history was non-specific. A physical examination revealed erythematous plaques containing multiple tiny white papules and scattered white papules on both hands and feet (Fig. 1). A histopathological examination of the erythematous plaques revealed multiple subepidermal stratified epithelium-lined cysts filled with concentric keratin and mild inflammation (Fig. 1d). The patient was diagnosed with both multiple eruptive milia (MEM) and milia en plaque (MEP) and is being regularly observed.
Correspondence: Hyojin Kim, M.D., Department of Dermatology, Busan Paik Hospital, Ga-geum 2 dong, Jin Gu, Busan 614-735, Korea. Email: [email protected]
© 2015 Japanese Dermatological Association
931
REFERENCES 1 Robson A, Greene J, Ansari N et al. Eccrine porocarcinoma (malignant eccrine poroma): a clinicopathologic study of 69 cases. Am J Surg Pathol 2001; 25: 710–720. 2 De Iuliis F, Amoroso L, Taglieri L et al. Chemotherapy of rare skin adnexal tumors: a review of literature. Anticancer Res 2014; 34: 5263–5268. 3 Plunkett TA, Hanby AM, Miles DW, Rubens RD. Metastatic eccrine porocarcinoma: response to docetaxel (Taxotere) chemotherapy. Ann Oncol 2001; 12: 411–414.
4 O’Neill VJ, Kaye SB, Reed NS, Paul J, Davis JA, Vasey PA. A dosefinding study of carboplatin-epirubicin-docetaxel in advanced epithelial ovarian cancer. Br J Cancer 2002; 86: 1385–1390. 5 Rossi A, Di Maio M, Chiodini P et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol 2012; 30: 1692–1698.
Cutaneous squamous cell carcinoma with extensive perineural invasion and perineural cyst formation without regional lymph node metastases Dear Editor, A new staging system for cutaneous squamous cell carcinoma (cSCC) was recently adopted by the American Joint Committee
(a)
on Cancer, in which perineural invasion (PNI) was newly added as a high-risk characteristic.1 Regional lymph node (LN) and distant metastases occur significantly more frequently in cSCC
(d) (g)
(b) (e)
(h)
(f)
(i)
(c)
Figure 1. (a) An exophytic, papillomatous, keratotic tumor measuring 16 cm 9 6 cm with central ulceration in the right popliteal fossa. (b) The excised tumor showed the enlarged nerve trunk extending centrally (black arrows). The section cut along the blue line is shown in (c). (c) Histopathology of the excised tumor and the nerve trunk showing infiltrative nests of atypical keratinocytes arising from the epidermis. Within and around the nerve, cysts mimicking epidermal cysts were formed. The panoramic photo showing the whole image of the band-like structure was created by stitching five overlapping photos (hematoxylin–eosin). (d) A peripheral nerve was invaded by tumor cells. Arrows indicate intraneural island of tumor cells (hematoxylin–eosin). (e) A nest of tumor cells was present inside the nerve (hematoxylin–eosin). (f) Immunohistochemical stain of (e) demonstrated nerve bundles (S-100 stain). (g) The cysts were lined by a stratified squamous epithelium and filled with keratin. Nerve tissues (blue circle) surrounded the cysts (hematoxylin–eosin). (h) Intraneural island of tumor cells in the nerve tissue near right inguinal LN (hematoxylin–eosin). (i) Immunohistochemical stain of (h) demonstrated nerve bundles (S-100 stain).
Correspondence: Fumi Miyagawa, M.D., Ph.D., Department of Dermatology, Nara Medical University School of Medicine, 840 Shijo, Kashihara, Nara 634-8522, Japan. Email: [email protected]
930
© 2015 Japanese Dermatological Association
Letters to the Editor
with PNI than in cSCC without PNI.2 We report a case of cSCC in which gross involvement of a large-caliber nerve was observed, but not metastatic spread to regional LN. We also found an intraneural cyst mimicking an epidermal cyst covering almost the entire nerve trunk. An 84-year-old man had noted a tumor in the right popliteal fossa 6 months previously. He experienced paresthesia in the right popliteal fossa during the 6 months, which had become painful 2 months prior to admission. A physical examination revealed a reddish, papillomatous tumor (Fig. 1a). Positron emission tomography and computed tomography showed no evidence of nodal and distant metastases. The tumor was excised. Intraoperatively, there was a firm, thick band-like structure running parallel with the great saphenous vein, originating from the tumor and extending centrally toward the inguinal region (Fig. 1b). Neural invasion involving the posterior femoral cutaneous nerve was suspected. The band-like structure was cut off at the middle of the thigh and he subsequently underwent sentinel LN dissection. Histopathology showed invading strands of atypical keratinocytes within the dermis and subcutis. In the subcutis, cystic space filled with keratin had formed within the enlarged nerve over a long distance, where no tumor was present in most areas (Fig. 1c). In some areas, tumor cells invaded the nerve and formed intraneural nests (Fig. 1d–f). It was also observed that cystic structures were partially surrounded by nerve tissues (Fig. 1g). No tumor cells were found in a right inguinal LN specimen. The nerve tissue near right inguinal LN taken during the sentinel LN dissection demonstrated an intraneural island of atypical keratinocytes (Fig. 1h,i), suggesting PNI over a long distance from the popliteal fossa to the inguinal region. Although postoperative radiotherapy was planned, he died from aspiration pneumonia while he was being temporarily discharged from the hospital. Perineural invasion is a form of spread of malignant tumors by growth in and around a nerve2,3 and has been estimated to occur in 2.5–14% of cSCC.3 Patients with PNI sometimes exhibit neurological symptoms, including pain, paresthesia and loss
of motor skills,2,4 as happened in our patient. Recent studies have shown that large-caliber PNI is associated with a 4–5-fold increased risk of nodal metastases and death compared with small-caliber PNI.5 However, despite the fact that the tumor cells invaded a large-caliber nerve and spread perineurally over a long distance, our patient did not have regional LN metastases. An interesting finding in our case is that a cyst was present over most of the area of the nerve involved. Because we did not find cysts in the primary lesion, the tumor cells within perineural tissue are likely to re-differentiate toward more differentiated SCC, which predisposed the PNI lesion to form a cyst.
CONFLICT OF INTEREST:
None.
Fumi MIYAGAWA,1 Chiharu HIROSE,1 Takaya FUKUMOTO,1 Hideki ASAI,2 Nobuhiko KOBAYASHI,1 Hideo ASADA1 1
Department of Dermatology, and 2The Center for Plastic Surgery, Nara Medical University School of Medicine, Nara, Japan doi: 10.1111/1346-8138.12981
REFERENCES 1 Farasat S, Yu SS, Neel VA et al. A new American Joint Committee on Cancer staging system for cutaneous squamous cell carcinoma: creation and rationale for inclusion of tumor (T) characteristics. J Am Acad Dermatol 2011; 64: 1051–1059. 2 Goepfert H, Dichtel WJ, Medina JE, Lindberg RD, Luna MD. Perineural invasion in squamous cell skin carcinoma of the head and neck. Am J Surg 1984; 148: 542–547. 3 Leibovitch I, Huilgol SC, Selva D, Hill D, Richards S, Paver R. Cutaneous squamous cell carcinoma treated with Mohs micrographic surgery in Australia II. Perineural invasion. J Am Acad Dermatol 2005; 53: 261–266. 4 Cottel WI. Perineural invasion by squamous-cell carcinoma. J Dermatol Surg Oncol 1982; 8: 589–600. 5 Carter JB, Johnson MM, Chua TL, Karia PS, Schmults CD. Outcomes of primary cutaneous squamous cell carcinoma with perineural invasion: an 11-year cohort study. JAMA Dermatol 2013; 149: 35–41.
Multiple eruptive milia and milia en plaque on the hands and feet of a 2-month-old female Dear Editor, A 2-month-old female presented with multiple papules on both hands and feet. One week earlier, white papules and erythematous plaques studded with white papules had developed on both acral areas and then spread. The patient’s history was unremarkable; there was no history of trauma, including friction or rubbing, sunlight exposure, topical use of medical ointments or drug intake before the development of the skin lesions. Also, her
family history was non-specific. A physical examination revealed erythematous plaques containing multiple tiny white papules and scattered white papules on both hands and feet (Fig. 1). A histopathological examination of the erythematous plaques revealed multiple subepidermal stratified epithelium-lined cysts filled with concentric keratin and mild inflammation (Fig. 1d). The patient was diagnosed with both multiple eruptive milia (MEM) and milia en plaque (MEP) and is being regularly observed.
Correspondence: Hyojin Kim, M.D., Department of Dermatology, Busan Paik Hospital, Ga-geum 2 dong, Jin Gu, Busan 614-735, Korea. Email: [email protected]
© 2015 Japanese Dermatological Association
931
