Craig J. Garofola, DO

Squamoid eccrine ductal carcinoma (SEDC) is an aggressive underrecognized cutaneous malignancy of unknown etiology.¹ It is most likely to occur in sun-exposed areas of the body, most commonly the head and neck. Risk factors include male sex, increased age, and chronic immunosuppression.^1-4 Current reports suggest that SEDC is likely a high-grade subtype of squamous cell carcinoma (SCC) with a high risk for local recurrence (25%) and metastasis (13%).^1,3,5,6 There are as few as 56 cases of SEDC reported in the literature; however, the number of cases may be closer to 100 due to SEDC being classified as either adenosquamous carcinoma of the skin or ductal eccrine carcinoma with squamous differentiation.¹

Clinically, SEDC mimics keratinocyte carcinomas. Histologically, SEDC is biphasic, with a superficial portion resembling well-differentiated SCC and a deeply invasive portion having infiltrative irregular cords with ductal differentiation. Perineural invasion (PNI) frequently is present. Multiple connections to the overlying epidermis also can be seen, serving as a subtle clue to the diagnosis on broad superficial specimens.^1-3 Due to superficial sampling, approximately 50% of reported cases are misdiagnosed as SCC during the initial biopsy.⁴ The diagnosis of SEDC often is made during complete excision when deeper tissue is sampled. Establishing an accurate diagnosis is important given the more aggressive nature of SEDC compared with SCC and its proclivity for PNI.^1,3,6 The purpose of this review is to increase awareness of this underrecognized entity and describe the histologic findings that help distinguish SEDC from SCC.

Patient Chart Review

We reviewed chart notes as well as frozen and formalin-fixed paraffin-embedded tissue sections from all 5 patients diagnosed with SEDC at a single institution between November 2018 and May 2020. The mean age of patients was 81 years, and 4 were male. Four of the patients presented for MMS with a preoperative diagnosis of SCC per the original biopsy results. Only 1 patient had a preoperative diagnosis of SEDC. The details of each case are recorded in the Table. All tumors were greater than 2 cm in diameter on initial presentation, were located on the head, and clinically resembled keratinocyte carcinoma with either a nodular or plaquelike appearance (Figure 1).

Intraoperative histologic examination of the excised tissue revealed a biphasic pattern consisting of superficial SCC features overlying deeper dermal and subcutaneous infiltrative malignant ductal elements with gland formation in all 5 patients (Figures 2–4). Immunohistochemical staining with cytokeratin AE1/AE3 revealed thin strands of carcinoma in the mid to deeper dermis with squamous differentiation and eccrine ductal differentiation (Figure 5), thus confirming the diagnosis in all 5 patients.

Literature Review

A PubMed review of the literature using the search term squamoid eccrine ductal carcinoma resulted in 28 articles, 19 of which were included in the review based on inclusion criteria (original articles available in English, in full text, and pertained to SEDC). Our review yielded 56 cases of SEDC.^1-19 The mean age of patients with SEDC was 72 years. The number of male and female cases was 52% (29/56) and 48% (27/56), respectively. The most common location of SEDC was on the head or neck (71% [40/56]), followed by the extremities (19% [11/56]). Immunosuppression was noted in 9% (5/56) of cases. Wide local excision was the most commonly employed treatment modality (91% [51/56]), with MMS being used in 4 patients (7%). Adjuvant radiation was reported in 5% (3/56) of cases. Perineural invasion was reported in 34% (19/56) of cases. Recurrence was seen in 23% (13/56) of cases, with a mean time to recurrence of 10.4 months. Metastasis to regional lymph nodes was observed in 13% (7/56) of cases, with 7% (4/56) of those cases having distant metastases.

Comment

Squamoid eccrine ductal carcinoma was successfully treated with MMS in all 5 of the patients we reviewed. Recognition of a distinct biphasic pattern consisting of squamous differentiation superficially with epidermal connection overlying deeper dermal and subcutaneous infiltrative malignant ductal elements with gland formation should lead to consideration of this diagnosis. A thorough inspection for PNI also should be performed, as this finding was present in all of 5 cases and in 34% of reported cases in our literature review.

The differential diagnosis for SEDC includes SCC, metastatic adenocarcinoma with squamoid features, and eccrine tumors, including eccrine poroma, microcystic adnexal carcinoma (MAC), and porocarcinoma with squamous differentiation. The combination of histologic features with the immunoexpression profile of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), cytokeratin (CK) 5/6, and p63 can effectively exclude the other entities in the differential and confirm the diagnosis of SEDC.^1,3,4 While the diagnosis of SEDC relies on the specific histologic features of multiple surface attachments and superficial squamoid changes with deep ductular elements, immunohistochemistry can nonetheless be adjunctive in difficult cases. Positive immunohistochemical staining for CEA and EMA can help to highlight and delineate true glandular elements, whereas CK5/6 highlights the overall contour of the tumor, displaying more clearly the multiple epidermal attachments and the subtle infiltrative nature of the deeper components of invasive cords and ducts. In addition, the combination of CK5/6 and p63 positivity supports the primary cutaneous nature of the lesion rather than metastatic adenocarcinoma.^13,20 Other markers of eccrine secretory coils, such as CK7, CAM5.2, and S100, also are sometimes used for confirmation, some of which can aid in distinction from noneccrine sweat gland differentiation, as CK7 and CAM5.2 are negative in both luminal and basal cells of the dermal duct while being positive within the secretory coil, and S100 protein is expressed within eccrine secretory coil but negative within the apocrine sweat glands.^2,4,21

The clinical findings from our chart review corroborated those reported in the literature. The mean age of SEDC in the 5 patients we reviewed was 81 years, and all cases presented on the head, consistent with the findings observed in the literature. Although 4 of our cases were male, there may not be a difference in risk based on sex as previously thought.¹ Our literature review revealed an almost equivalent percentage of male and female cases, with 52% being male.

Immunosuppression has been associated with an increased risk for SEDC. Our literature review revealed that approximately 9% (5/56) of cases occurred in immunosuppressed individuals. Two of these reported cases were in the setting of underlying chronic lymphocytic leukemia, 2 in individuals with a history of organ transplant, and 1 treated with azathioprine for myasthenia gravis.^2,4,10,12,13 Our chart review supported this correlation, as all 5 patients had a medical history potentially consistent with being in an immunocompromised state (Table). Notably, patient 5 represents a unique case of SEDC occurring in the setting of HIV. The patient had HIV for 33 years, with his most recent CD4⁺ count of 794 mm³ and HIV-1 RNA load of 35 copies/mL. Given that HIV-positive individuals may have more than a 2-fold increased risk of SCC, a greater degree of suspicion for SEDC should be maintained for these patients.^22,23

The etiology of SEDC is controversial but is thought to be either an SCC arising from eccrine glands or a variant of eccrine carcinoma with extensive squamoid differentiation.^{4,6,13,14,17,24} While SEDC certainly appears to share the proclivity for PNI with the malignant eccrine tumor MAC, it is simultaneously quite distinct, demonstrating nuclear pleomorphism and mitotic activity, both of which are lacking in the bland nature of MACs.^12,25

The exact prevalence of SEDC is difficult to ascertain because of its frequent misdiagnosis and variable nomenclature used within the literature. Most reported cases of SEDC are mistakenly diagnosed as SCC on the initial shave or punch biopsy because of superficial sampling. This also was the case in 4 of the patients we reviewed. In addition, there are reported cases of SEDC that were referred to by the investigators as cutaneous adenosquamous carcinoma (cASC), among other descriptors, such as ductal eccrine carcinoma with squamous differentiation, adnexal carcinoma with squamous and ductal differentiation, and syringoid eccrine carcinoma.^26-32 While the World Health Organization classifies SEDC as a distinct variant of cASC, which is a rare variant of SCC in itself, the 2 can be differentiated. Despite the similar clinical and histologic features shared between cASC and SEDC, the neoplastic aggregates in SEDC exhibit ductal differentiation containing lumina positive for CEA and EMA.⁴ Overall, we favor the term squamoid eccrine ductal carcinoma, as there has recently been more uniformity for the designation of this disease entity as such.

It is unclear whether the high incidence of local recurrence (23% [13/56]) of SEDC reported in the literature is related to the treatment modality employed (ie, wide local excision) or due to the innate aggressiveness of SEDC.^1,3,5 The literature has shown that MMS has lower recurrence rates than other treatments at 5-year follow-up for SCC (3.1%–5%) and eccrine carcinomas (0%–5%).^33,34 Although studies assessing tumor behavior or comparing treatment modalities are limited because of the rarity and underrecognition of SEDC, MMS has been used several times for SEDC with only 1 recurrence reported.^4,13,17,24 Given that all 5 of the patients we reviewed required more than 1 Mohs stage for complete tumor clearance and none demonstrated evidence of recurrence or metastasis (Table), we recommend MMS as the treatment of choice for SEDC.

Conclusion

Squamoid eccrine ductal carcinoma is a rare but likely underdiagnosed cutaneous tumor of uncertain etiology. Because of its propensity for recurrence and metastasis, excision of SEDC with complete circumferential peripheral and deep margin assessment with close follow-up is recommended.

Squamoid eccrine ductal carcinoma (SEDC) is an aggressive underrecognized cutaneous malignancy of unknown etiology.¹ It is most likely to occur in sun-exposed areas of the body, most commonly the head and neck. Risk factors include male sex, increased age, and chronic immunosuppression.^1-4 Current reports suggest that SEDC is likely a high-grade subtype of squamous cell carcinoma (SCC) with a high risk for local recurrence (25%) and metastasis (13%).^1,3,5,6 There are as few as 56 cases of SEDC reported in the literature; however, the number of cases may be closer to 100 due to SEDC being classified as either adenosquamous carcinoma of the skin or ductal eccrine carcinoma with squamous differentiation.¹

Clinically, SEDC mimics keratinocyte carcinomas. Histologically, SEDC is biphasic, with a superficial portion resembling well-differentiated SCC and a deeply invasive portion having infiltrative irregular cords with ductal differentiation. Perineural invasion (PNI) frequently is present. Multiple connections to the overlying epidermis also can be seen, serving as a subtle clue to the diagnosis on broad superficial specimens.^1-3 Due to superficial sampling, approximately 50% of reported cases are misdiagnosed as SCC during the initial biopsy.⁴ The diagnosis of SEDC often is made during complete excision when deeper tissue is sampled. Establishing an accurate diagnosis is important given the more aggressive nature of SEDC compared with SCC and its proclivity for PNI.^1,3,6 The purpose of this review is to increase awareness of this underrecognized entity and describe the histologic findings that help distinguish SEDC from SCC.

Patient Chart Review

We reviewed chart notes as well as frozen and formalin-fixed paraffin-embedded tissue sections from all 5 patients diagnosed with SEDC at a single institution between November 2018 and May 2020. The mean age of patients was 81 years, and 4 were male. Four of the patients presented for MMS with a preoperative diagnosis of SCC per the original biopsy results. Only 1 patient had a preoperative diagnosis of SEDC. The details of each case are recorded in the Table. All tumors were greater than 2 cm in diameter on initial presentation, were located on the head, and clinically resembled keratinocyte carcinoma with either a nodular or plaquelike appearance (Figure 1).

Intraoperative histologic examination of the excised tissue revealed a biphasic pattern consisting of superficial SCC features overlying deeper dermal and subcutaneous infiltrative malignant ductal elements with gland formation in all 5 patients (Figures 2–4). Immunohistochemical staining with cytokeratin AE1/AE3 revealed thin strands of carcinoma in the mid to deeper dermis with squamous differentiation and eccrine ductal differentiation (Figure 5), thus confirming the diagnosis in all 5 patients.

Literature Review

A PubMed review of the literature using the search term squamoid eccrine ductal carcinoma resulted in 28 articles, 19 of which were included in the review based on inclusion criteria (original articles available in English, in full text, and pertained to SEDC). Our review yielded 56 cases of SEDC.^1-19 The mean age of patients with SEDC was 72 years. The number of male and female cases was 52% (29/56) and 48% (27/56), respectively. The most common location of SEDC was on the head or neck (71% [40/56]), followed by the extremities (19% [11/56]). Immunosuppression was noted in 9% (5/56) of cases. Wide local excision was the most commonly employed treatment modality (91% [51/56]), with MMS being used in 4 patients (7%). Adjuvant radiation was reported in 5% (3/56) of cases. Perineural invasion was reported in 34% (19/56) of cases. Recurrence was seen in 23% (13/56) of cases, with a mean time to recurrence of 10.4 months. Metastasis to regional lymph nodes was observed in 13% (7/56) of cases, with 7% (4/56) of those cases having distant metastases.

Comment

Squamoid eccrine ductal carcinoma was successfully treated with MMS in all 5 of the patients we reviewed. Recognition of a distinct biphasic pattern consisting of squamous differentiation superficially with epidermal connection overlying deeper dermal and subcutaneous infiltrative malignant ductal elements with gland formation should lead to consideration of this diagnosis. A thorough inspection for PNI also should be performed, as this finding was present in all of 5 cases and in 34% of reported cases in our literature review.

The differential diagnosis for SEDC includes SCC, metastatic adenocarcinoma with squamoid features, and eccrine tumors, including eccrine poroma, microcystic adnexal carcinoma (MAC), and porocarcinoma with squamous differentiation. The combination of histologic features with the immunoexpression profile of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), cytokeratin (CK) 5/6, and p63 can effectively exclude the other entities in the differential and confirm the diagnosis of SEDC.^1,3,4 While the diagnosis of SEDC relies on the specific histologic features of multiple surface attachments and superficial squamoid changes with deep ductular elements, immunohistochemistry can nonetheless be adjunctive in difficult cases. Positive immunohistochemical staining for CEA and EMA can help to highlight and delineate true glandular elements, whereas CK5/6 highlights the overall contour of the tumor, displaying more clearly the multiple epidermal attachments and the subtle infiltrative nature of the deeper components of invasive cords and ducts. In addition, the combination of CK5/6 and p63 positivity supports the primary cutaneous nature of the lesion rather than metastatic adenocarcinoma.^13,20 Other markers of eccrine secretory coils, such as CK7, CAM5.2, and S100, also are sometimes used for confirmation, some of which can aid in distinction from noneccrine sweat gland differentiation, as CK7 and CAM5.2 are negative in both luminal and basal cells of the dermal duct while being positive within the secretory coil, and S100 protein is expressed within eccrine secretory coil but negative within the apocrine sweat glands.^2,4,21

The clinical findings from our chart review corroborated those reported in the literature. The mean age of SEDC in the 5 patients we reviewed was 81 years, and all cases presented on the head, consistent with the findings observed in the literature. Although 4 of our cases were male, there may not be a difference in risk based on sex as previously thought.¹ Our literature review revealed an almost equivalent percentage of male and female cases, with 52% being male.

Immunosuppression has been associated with an increased risk for SEDC. Our literature review revealed that approximately 9% (5/56) of cases occurred in immunosuppressed individuals. Two of these reported cases were in the setting of underlying chronic lymphocytic leukemia, 2 in individuals with a history of organ transplant, and 1 treated with azathioprine for myasthenia gravis.^2,4,10,12,13 Our chart review supported this correlation, as all 5 patients had a medical history potentially consistent with being in an immunocompromised state (Table). Notably, patient 5 represents a unique case of SEDC occurring in the setting of HIV. The patient had HIV for 33 years, with his most recent CD4⁺ count of 794 mm³ and HIV-1 RNA load of 35 copies/mL. Given that HIV-positive individuals may have more than a 2-fold increased risk of SCC, a greater degree of suspicion for SEDC should be maintained for these patients.^22,23

The etiology of SEDC is controversial but is thought to be either an SCC arising from eccrine glands or a variant of eccrine carcinoma with extensive squamoid differentiation.^{4,6,13,14,17,24} While SEDC certainly appears to share the proclivity for PNI with the malignant eccrine tumor MAC, it is simultaneously quite distinct, demonstrating nuclear pleomorphism and mitotic activity, both of which are lacking in the bland nature of MACs.^12,25

The exact prevalence of SEDC is difficult to ascertain because of its frequent misdiagnosis and variable nomenclature used within the literature. Most reported cases of SEDC are mistakenly diagnosed as SCC on the initial shave or punch biopsy because of superficial sampling. This also was the case in 4 of the patients we reviewed. In addition, there are reported cases of SEDC that were referred to by the investigators as cutaneous adenosquamous carcinoma (cASC), among other descriptors, such as ductal eccrine carcinoma with squamous differentiation, adnexal carcinoma with squamous and ductal differentiation, and syringoid eccrine carcinoma.^26-32 While the World Health Organization classifies SEDC as a distinct variant of cASC, which is a rare variant of SCC in itself, the 2 can be differentiated. Despite the similar clinical and histologic features shared between cASC and SEDC, the neoplastic aggregates in SEDC exhibit ductal differentiation containing lumina positive for CEA and EMA.⁴ Overall, we favor the term squamoid eccrine ductal carcinoma, as there has recently been more uniformity for the designation of this disease entity as such.

It is unclear whether the high incidence of local recurrence (23% [13/56]) of SEDC reported in the literature is related to the treatment modality employed (ie, wide local excision) or due to the innate aggressiveness of SEDC.^1,3,5 The literature has shown that MMS has lower recurrence rates than other treatments at 5-year follow-up for SCC (3.1%–5%) and eccrine carcinomas (0%–5%).^33,34 Although studies assessing tumor behavior or comparing treatment modalities are limited because of the rarity and underrecognition of SEDC, MMS has been used several times for SEDC with only 1 recurrence reported.^4,13,17,24 Given that all 5 of the patients we reviewed required more than 1 Mohs stage for complete tumor clearance and none demonstrated evidence of recurrence or metastasis (Table), we recommend MMS as the treatment of choice for SEDC.

Conclusion

Squamoid eccrine ductal carcinoma is a rare but likely underdiagnosed cutaneous tumor of uncertain etiology. Because of its propensity for recurrence and metastasis, excision of SEDC with complete circumferential peripheral and deep margin assessment with close follow-up is recommended.

Squamoid eccrine ductal carcinoma (SEDC) is an aggressive underrecognized cutaneous malignancy of unknown etiology.¹ It is most likely to occur in sun-exposed areas of the body, most commonly the head and neck. Risk factors include male sex, increased age, and chronic immunosuppression.^1-4 Current reports suggest that SEDC is likely a high-grade subtype of squamous cell carcinoma (SCC) with a high risk for local recurrence (25%) and metastasis (13%).^1,3,5,6 There are as few as 56 cases of SEDC reported in the literature; however, the number of cases may be closer to 100 due to SEDC being classified as either adenosquamous carcinoma of the skin or ductal eccrine carcinoma with squamous differentiation.¹

Clinically, SEDC mimics keratinocyte carcinomas. Histologically, SEDC is biphasic, with a superficial portion resembling well-differentiated SCC and a deeply invasive portion having infiltrative irregular cords with ductal differentiation. Perineural invasion (PNI) frequently is present. Multiple connections to the overlying epidermis also can be seen, serving as a subtle clue to the diagnosis on broad superficial specimens.^1-3 Due to superficial sampling, approximately 50% of reported cases are misdiagnosed as SCC during the initial biopsy.⁴ The diagnosis of SEDC often is made during complete excision when deeper tissue is sampled. Establishing an accurate diagnosis is important given the more aggressive nature of SEDC compared with SCC and its proclivity for PNI.^1,3,6 The purpose of this review is to increase awareness of this underrecognized entity and describe the histologic findings that help distinguish SEDC from SCC.

Patient Chart Review

We reviewed chart notes as well as frozen and formalin-fixed paraffin-embedded tissue sections from all 5 patients diagnosed with SEDC at a single institution between November 2018 and May 2020. The mean age of patients was 81 years, and 4 were male. Four of the patients presented for MMS with a preoperative diagnosis of SCC per the original biopsy results. Only 1 patient had a preoperative diagnosis of SEDC. The details of each case are recorded in the Table. All tumors were greater than 2 cm in diameter on initial presentation, were located on the head, and clinically resembled keratinocyte carcinoma with either a nodular or plaquelike appearance (Figure 1).

Intraoperative histologic examination of the excised tissue revealed a biphasic pattern consisting of superficial SCC features overlying deeper dermal and subcutaneous infiltrative malignant ductal elements with gland formation in all 5 patients (Figures 2–4). Immunohistochemical staining with cytokeratin AE1/AE3 revealed thin strands of carcinoma in the mid to deeper dermis with squamous differentiation and eccrine ductal differentiation (Figure 5), thus confirming the diagnosis in all 5 patients.

Literature Review

A PubMed review of the literature using the search term squamoid eccrine ductal carcinoma resulted in 28 articles, 19 of which were included in the review based on inclusion criteria (original articles available in English, in full text, and pertained to SEDC). Our review yielded 56 cases of SEDC.^1-19 The mean age of patients with SEDC was 72 years. The number of male and female cases was 52% (29/56) and 48% (27/56), respectively. The most common location of SEDC was on the head or neck (71% [40/56]), followed by the extremities (19% [11/56]). Immunosuppression was noted in 9% (5/56) of cases. Wide local excision was the most commonly employed treatment modality (91% [51/56]), with MMS being used in 4 patients (7%). Adjuvant radiation was reported in 5% (3/56) of cases. Perineural invasion was reported in 34% (19/56) of cases. Recurrence was seen in 23% (13/56) of cases, with a mean time to recurrence of 10.4 months. Metastasis to regional lymph nodes was observed in 13% (7/56) of cases, with 7% (4/56) of those cases having distant metastases.

Comment

Squamoid eccrine ductal carcinoma was successfully treated with MMS in all 5 of the patients we reviewed. Recognition of a distinct biphasic pattern consisting of squamous differentiation superficially with epidermal connection overlying deeper dermal and subcutaneous infiltrative malignant ductal elements with gland formation should lead to consideration of this diagnosis. A thorough inspection for PNI also should be performed, as this finding was present in all of 5 cases and in 34% of reported cases in our literature review.

The differential diagnosis for SEDC includes SCC, metastatic adenocarcinoma with squamoid features, and eccrine tumors, including eccrine poroma, microcystic adnexal carcinoma (MAC), and porocarcinoma with squamous differentiation. The combination of histologic features with the immunoexpression profile of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), cytokeratin (CK) 5/6, and p63 can effectively exclude the other entities in the differential and confirm the diagnosis of SEDC.^1,3,4 While the diagnosis of SEDC relies on the specific histologic features of multiple surface attachments and superficial squamoid changes with deep ductular elements, immunohistochemistry can nonetheless be adjunctive in difficult cases. Positive immunohistochemical staining for CEA and EMA can help to highlight and delineate true glandular elements, whereas CK5/6 highlights the overall contour of the tumor, displaying more clearly the multiple epidermal attachments and the subtle infiltrative nature of the deeper components of invasive cords and ducts. In addition, the combination of CK5/6 and p63 positivity supports the primary cutaneous nature of the lesion rather than metastatic adenocarcinoma.^13,20 Other markers of eccrine secretory coils, such as CK7, CAM5.2, and S100, also are sometimes used for confirmation, some of which can aid in distinction from noneccrine sweat gland differentiation, as CK7 and CAM5.2 are negative in both luminal and basal cells of the dermal duct while being positive within the secretory coil, and S100 protein is expressed within eccrine secretory coil but negative within the apocrine sweat glands.^2,4,21

The clinical findings from our chart review corroborated those reported in the literature. The mean age of SEDC in the 5 patients we reviewed was 81 years, and all cases presented on the head, consistent with the findings observed in the literature. Although 4 of our cases were male, there may not be a difference in risk based on sex as previously thought.¹ Our literature review revealed an almost equivalent percentage of male and female cases, with 52% being male.

Immunosuppression has been associated with an increased risk for SEDC. Our literature review revealed that approximately 9% (5/56) of cases occurred in immunosuppressed individuals. Two of these reported cases were in the setting of underlying chronic lymphocytic leukemia, 2 in individuals with a history of organ transplant, and 1 treated with azathioprine for myasthenia gravis.^2,4,10,12,13 Our chart review supported this correlation, as all 5 patients had a medical history potentially consistent with being in an immunocompromised state (Table). Notably, patient 5 represents a unique case of SEDC occurring in the setting of HIV. The patient had HIV for 33 years, with his most recent CD4⁺ count of 794 mm³ and HIV-1 RNA load of 35 copies/mL. Given that HIV-positive individuals may have more than a 2-fold increased risk of SCC, a greater degree of suspicion for SEDC should be maintained for these patients.^22,23

The etiology of SEDC is controversial but is thought to be either an SCC arising from eccrine glands or a variant of eccrine carcinoma with extensive squamoid differentiation.^{4,6,13,14,17,24} While SEDC certainly appears to share the proclivity for PNI with the malignant eccrine tumor MAC, it is simultaneously quite distinct, demonstrating nuclear pleomorphism and mitotic activity, both of which are lacking in the bland nature of MACs.^12,25

The exact prevalence of SEDC is difficult to ascertain because of its frequent misdiagnosis and variable nomenclature used within the literature. Most reported cases of SEDC are mistakenly diagnosed as SCC on the initial shave or punch biopsy because of superficial sampling. This also was the case in 4 of the patients we reviewed. In addition, there are reported cases of SEDC that were referred to by the investigators as cutaneous adenosquamous carcinoma (cASC), among other descriptors, such as ductal eccrine carcinoma with squamous differentiation, adnexal carcinoma with squamous and ductal differentiation, and syringoid eccrine carcinoma.^26-32 While the World Health Organization classifies SEDC as a distinct variant of cASC, which is a rare variant of SCC in itself, the 2 can be differentiated. Despite the similar clinical and histologic features shared between cASC and SEDC, the neoplastic aggregates in SEDC exhibit ductal differentiation containing lumina positive for CEA and EMA.⁴ Overall, we favor the term squamoid eccrine ductal carcinoma, as there has recently been more uniformity for the designation of this disease entity as such.

It is unclear whether the high incidence of local recurrence (23% [13/56]) of SEDC reported in the literature is related to the treatment modality employed (ie, wide local excision) or due to the innate aggressiveness of SEDC.^1,3,5 The literature has shown that MMS has lower recurrence rates than other treatments at 5-year follow-up for SCC (3.1%–5%) and eccrine carcinomas (0%–5%).^33,34 Although studies assessing tumor behavior or comparing treatment modalities are limited because of the rarity and underrecognition of SEDC, MMS has been used several times for SEDC with only 1 recurrence reported.^4,13,17,24 Given that all 5 of the patients we reviewed required more than 1 Mohs stage for complete tumor clearance and none demonstrated evidence of recurrence or metastasis (Table), we recommend MMS as the treatment of choice for SEDC.

Conclusion

Squamoid eccrine ductal carcinoma is a rare but likely underdiagnosed cutaneous tumor of uncertain etiology. Because of its propensity for recurrence and metastasis, excision of SEDC with complete circumferential peripheral and deep margin assessment with close follow-up is recommended.

The Diagnosis: Proliferating Pilar Tumor  

Proliferating pilar tumor (PPT), or cyst, is a neoplasm of trichilemmal keratinization first described by Wilson-Jones¹ in 1966. Proliferating pilar tumors lie on a spectrum with malignant PPT, which is a rare adnexal neoplasm first described by Saida et al² in 1983. The incidence of PPT is unknown given the paucity of cases and the possible misdiagnosis as squamous cell carcinoma (SCC). Proliferating pilar tumors tend to present on the head and neck of older females as a multilobular and sometimes ulcerating nodule.³ Although PPT can occur de novo, the majority of cases are thought to develop progressively from a benign pilar cyst. Histopathologically, PPT is characterized by cords and nests of squamous cells that display trichilemmal keratinization (quiz images).  

Classification of PPT as benign or malignant is challenging, though criteria have been proposed.^3-7 Lesions with minimal infiltration into the surrounding dermis and scant mitosis typically behave in a benign manner, while lesions showing nuclear atypia, atypical mitosis, and irregular infiltration into the surrounding dermis can have up to a 50% locoregional recurrence rate.³ In addition, distinguishing a PPT from an SCC or trichilemmal carcinoma also can be difficult; however, SCC is favored when there is a lack of trichilemmal keratinization or when squamous atypia is present in the adjacent epidermis.⁸ Trichilemmal carcinoma is a rare tumor that has been questioned as a distinct entity.^9-12  

Pilomatricoma, also known as calcifying epithelioma of Malherbe, is a benign pilar tumor that presents as a slowly growing nodule on the head or neck area or arms.^13,14 Most pilomatricomas develop by the second decade of life. Multiple lesions may be present in association with myotonic dystrophy or Gardner syndrome among other syndromes.^15-17 Similar to PPT, pilomatricomas present as large dermal nodules; however, they tend to be circumscribed and have a trabecular network that consists of basophilic cells and eosinophilic keratinized shadow cells (Figure 1).¹⁸ Calcification may be seen and bone formation subsequently may occur.¹⁹  

Most sources now consider keratoacanthoma (KA) as a well-differentiated SCC.²⁰ The typical presentation consists of a rapidly growing erythematous to flesh-colored nodule with a central keratinous plug that develops over a period of weeks. If untreated, KAs may resolve over a period of months and leave a depressed scar. Local destruction can result from KAs, and they have the potential to transform into a more aggressive SCC. Accordingly, most clinicians use tissue destructive methods, excision, or Mohs micrographic surgery for treatment based on location. Histologically, a well-circumscribed proliferation of glassy cytoplasm is noted. A depressed keratin-filled center is surrounded by a lip of epithelium extending over the lesion (Figure 2).^20,21 Pseudoepitheliomatous hyperplasia accompanied by hypergranulosis is seen in the center of KAs rather than at the periphery, which is typical of non-KA SCCs. Typical KAs lack acantholysis, a feature suggesting a non-KA type of SCC. Neutrophilic microabscesses and eosinophils commonly are seen in KAs.^20,21  

Inverted follicular keratosis is a benign tumor that gained traction as its own entity in the 1960s.²² These lesions typically develop from the follicular infundibulum, but some consider them a version of a wart or seborrheic keratosis.²³ They generally are flesh-colored nodules on the upper cutaneous lip or face. Treatment usually consists of complete excision. There are many different growth patterns described, but they typically are endophytic tumors with eosinophilic squamous cells in the center and more basophilic cells at the periphery (Figure 3).²⁴ Characteristically, there are squamous eddies throughout the tumor (Figure 3 [inset]). There also may be a scant lymphohistiocytic infiltrate within the dermis surrounding the lesion.  

Trichilemmomas are flesh-colored adnexal neoplasms that may present as a solitary lesion or in clusters on the face. They have been reported to occur on all nonglabrous skin sites.²⁵ Multiple lesions may occur in association with Cowden syndrome or with nevus sebaceous.²⁶ A desmoplastic variant of trichilemmomas has been reported.²⁷ Desmoplastic trichilemmomas appear as well-circumscribed tumors of outer root sheath differentiation with lobules extending down into the dermis.²⁸ Vacuolated glycogen-filled keratinocytes are scattered throughout the lesion but are most prominent at the base. At the periphery of the lobules, peripheral palisading of basaloid cells is accompanied by a thickened eosinophilic basement membrane that is periodic acid-Schiff positive. Typical trichilemmomas also can display these features; however, the main differentiating feature of a desmoplastic trichilemmoma is the pink hyalinized stroma separating small islets of basophilic cells (Figure 4). Differentiation from an invasive malignant carcinoma sometimes can be challenging without a focus of typical trichilemmoma or if the biopsy specimen is too superficial.²⁹ 

Pilar cysts are common tumors that typically arise on the scalp and sometimes are proliferating. Proliferating pilar tumor should be kept on the differential when secondary changes such as ulceration occur in the primary lesion of the scalp. Microscopically, and sometimes clinically, PPT can be difficult to differentiate from other mimickers.  

The Diagnosis: Proliferating Pilar Tumor  

Proliferating pilar tumor (PPT), or cyst, is a neoplasm of trichilemmal keratinization first described by Wilson-Jones¹ in 1966. Proliferating pilar tumors lie on a spectrum with malignant PPT, which is a rare adnexal neoplasm first described by Saida et al² in 1983. The incidence of PPT is unknown given the paucity of cases and the possible misdiagnosis as squamous cell carcinoma (SCC). Proliferating pilar tumors tend to present on the head and neck of older females as a multilobular and sometimes ulcerating nodule.³ Although PPT can occur de novo, the majority of cases are thought to develop progressively from a benign pilar cyst. Histopathologically, PPT is characterized by cords and nests of squamous cells that display trichilemmal keratinization (quiz images).  

Classification of PPT as benign or malignant is challenging, though criteria have been proposed.^3-7 Lesions with minimal infiltration into the surrounding dermis and scant mitosis typically behave in a benign manner, while lesions showing nuclear atypia, atypical mitosis, and irregular infiltration into the surrounding dermis can have up to a 50% locoregional recurrence rate.³ In addition, distinguishing a PPT from an SCC or trichilemmal carcinoma also can be difficult; however, SCC is favored when there is a lack of trichilemmal keratinization or when squamous atypia is present in the adjacent epidermis.⁸ Trichilemmal carcinoma is a rare tumor that has been questioned as a distinct entity.^9-12  

Pilomatricoma, also known as calcifying epithelioma of Malherbe, is a benign pilar tumor that presents as a slowly growing nodule on the head or neck area or arms.^13,14 Most pilomatricomas develop by the second decade of life. Multiple lesions may be present in association with myotonic dystrophy or Gardner syndrome among other syndromes.^15-17 Similar to PPT, pilomatricomas present as large dermal nodules; however, they tend to be circumscribed and have a trabecular network that consists of basophilic cells and eosinophilic keratinized shadow cells (Figure 1).¹⁸ Calcification may be seen and bone formation subsequently may occur.¹⁹  

Most sources now consider keratoacanthoma (KA) as a well-differentiated SCC.²⁰ The typical presentation consists of a rapidly growing erythematous to flesh-colored nodule with a central keratinous plug that develops over a period of weeks. If untreated, KAs may resolve over a period of months and leave a depressed scar. Local destruction can result from KAs, and they have the potential to transform into a more aggressive SCC. Accordingly, most clinicians use tissue destructive methods, excision, or Mohs micrographic surgery for treatment based on location. Histologically, a well-circumscribed proliferation of glassy cytoplasm is noted. A depressed keratin-filled center is surrounded by a lip of epithelium extending over the lesion (Figure 2).^20,21 Pseudoepitheliomatous hyperplasia accompanied by hypergranulosis is seen in the center of KAs rather than at the periphery, which is typical of non-KA SCCs. Typical KAs lack acantholysis, a feature suggesting a non-KA type of SCC. Neutrophilic microabscesses and eosinophils commonly are seen in KAs.^20,21  

Inverted follicular keratosis is a benign tumor that gained traction as its own entity in the 1960s.²² These lesions typically develop from the follicular infundibulum, but some consider them a version of a wart or seborrheic keratosis.²³ They generally are flesh-colored nodules on the upper cutaneous lip or face. Treatment usually consists of complete excision. There are many different growth patterns described, but they typically are endophytic tumors with eosinophilic squamous cells in the center and more basophilic cells at the periphery (Figure 3).²⁴ Characteristically, there are squamous eddies throughout the tumor (Figure 3 [inset]). There also may be a scant lymphohistiocytic infiltrate within the dermis surrounding the lesion.  

Trichilemmomas are flesh-colored adnexal neoplasms that may present as a solitary lesion or in clusters on the face. They have been reported to occur on all nonglabrous skin sites.²⁵ Multiple lesions may occur in association with Cowden syndrome or with nevus sebaceous.²⁶ A desmoplastic variant of trichilemmomas has been reported.²⁷ Desmoplastic trichilemmomas appear as well-circumscribed tumors of outer root sheath differentiation with lobules extending down into the dermis.²⁸ Vacuolated glycogen-filled keratinocytes are scattered throughout the lesion but are most prominent at the base. At the periphery of the lobules, peripheral palisading of basaloid cells is accompanied by a thickened eosinophilic basement membrane that is periodic acid-Schiff positive. Typical trichilemmomas also can display these features; however, the main differentiating feature of a desmoplastic trichilemmoma is the pink hyalinized stroma separating small islets of basophilic cells (Figure 4). Differentiation from an invasive malignant carcinoma sometimes can be challenging without a focus of typical trichilemmoma or if the biopsy specimen is too superficial.²⁹ 

Pilar cysts are common tumors that typically arise on the scalp and sometimes are proliferating. Proliferating pilar tumor should be kept on the differential when secondary changes such as ulceration occur in the primary lesion of the scalp. Microscopically, and sometimes clinically, PPT can be difficult to differentiate from other mimickers.  

The Diagnosis: Proliferating Pilar Tumor  

Proliferating pilar tumor (PPT), or cyst, is a neoplasm of trichilemmal keratinization first described by Wilson-Jones¹ in 1966. Proliferating pilar tumors lie on a spectrum with malignant PPT, which is a rare adnexal neoplasm first described by Saida et al² in 1983. The incidence of PPT is unknown given the paucity of cases and the possible misdiagnosis as squamous cell carcinoma (SCC). Proliferating pilar tumors tend to present on the head and neck of older females as a multilobular and sometimes ulcerating nodule.³ Although PPT can occur de novo, the majority of cases are thought to develop progressively from a benign pilar cyst. Histopathologically, PPT is characterized by cords and nests of squamous cells that display trichilemmal keratinization (quiz images).  

Classification of PPT as benign or malignant is challenging, though criteria have been proposed.^3-7 Lesions with minimal infiltration into the surrounding dermis and scant mitosis typically behave in a benign manner, while lesions showing nuclear atypia, atypical mitosis, and irregular infiltration into the surrounding dermis can have up to a 50% locoregional recurrence rate.³ In addition, distinguishing a PPT from an SCC or trichilemmal carcinoma also can be difficult; however, SCC is favored when there is a lack of trichilemmal keratinization or when squamous atypia is present in the adjacent epidermis.⁸ Trichilemmal carcinoma is a rare tumor that has been questioned as a distinct entity.^9-12  

Pilomatricoma, also known as calcifying epithelioma of Malherbe, is a benign pilar tumor that presents as a slowly growing nodule on the head or neck area or arms.^13,14 Most pilomatricomas develop by the second decade of life. Multiple lesions may be present in association with myotonic dystrophy or Gardner syndrome among other syndromes.^15-17 Similar to PPT, pilomatricomas present as large dermal nodules; however, they tend to be circumscribed and have a trabecular network that consists of basophilic cells and eosinophilic keratinized shadow cells (Figure 1).¹⁸ Calcification may be seen and bone formation subsequently may occur.¹⁹  

Most sources now consider keratoacanthoma (KA) as a well-differentiated SCC.²⁰ The typical presentation consists of a rapidly growing erythematous to flesh-colored nodule with a central keratinous plug that develops over a period of weeks. If untreated, KAs may resolve over a period of months and leave a depressed scar. Local destruction can result from KAs, and they have the potential to transform into a more aggressive SCC. Accordingly, most clinicians use tissue destructive methods, excision, or Mohs micrographic surgery for treatment based on location. Histologically, a well-circumscribed proliferation of glassy cytoplasm is noted. A depressed keratin-filled center is surrounded by a lip of epithelium extending over the lesion (Figure 2).^20,21 Pseudoepitheliomatous hyperplasia accompanied by hypergranulosis is seen in the center of KAs rather than at the periphery, which is typical of non-KA SCCs. Typical KAs lack acantholysis, a feature suggesting a non-KA type of SCC. Neutrophilic microabscesses and eosinophils commonly are seen in KAs.^20,21  

Inverted follicular keratosis is a benign tumor that gained traction as its own entity in the 1960s.²² These lesions typically develop from the follicular infundibulum, but some consider them a version of a wart or seborrheic keratosis.²³ They generally are flesh-colored nodules on the upper cutaneous lip or face. Treatment usually consists of complete excision. There are many different growth patterns described, but they typically are endophytic tumors with eosinophilic squamous cells in the center and more basophilic cells at the periphery (Figure 3).²⁴ Characteristically, there are squamous eddies throughout the tumor (Figure 3 [inset]). There also may be a scant lymphohistiocytic infiltrate within the dermis surrounding the lesion.  

Trichilemmomas are flesh-colored adnexal neoplasms that may present as a solitary lesion or in clusters on the face. They have been reported to occur on all nonglabrous skin sites.²⁵ Multiple lesions may occur in association with Cowden syndrome or with nevus sebaceous.²⁶ A desmoplastic variant of trichilemmomas has been reported.²⁷ Desmoplastic trichilemmomas appear as well-circumscribed tumors of outer root sheath differentiation with lobules extending down into the dermis.²⁸ Vacuolated glycogen-filled keratinocytes are scattered throughout the lesion but are most prominent at the base. At the periphery of the lobules, peripheral palisading of basaloid cells is accompanied by a thickened eosinophilic basement membrane that is periodic acid-Schiff positive. Typical trichilemmomas also can display these features; however, the main differentiating feature of a desmoplastic trichilemmoma is the pink hyalinized stroma separating small islets of basophilic cells (Figure 4). Differentiation from an invasive malignant carcinoma sometimes can be challenging without a focus of typical trichilemmoma or if the biopsy specimen is too superficial.²⁹ 

Pilar cysts are common tumors that typically arise on the scalp and sometimes are proliferating. Proliferating pilar tumor should be kept on the differential when secondary changes such as ulceration occur in the primary lesion of the scalp. Microscopically, and sometimes clinically, PPT can be difficult to differentiate from other mimickers.